3 Days in Space Were Enough to Change 4 Astronauts’ Bodies and Minds
An extensive examination of medical data gathered from the private Inspiration4 mission in 2021 revealed temporary cognitive declines and genetic changes in the crew.
Supported by3 Days in Space Were Enough to Change 4 Astronauts’ Bodies and MindsAn extensive examination of medical data gathered from the private Inspiration4 mission in 2021 revealed temporary cognitive declines and genetic changes in the crew.ByKenneth ChangSpace changes you, even during short trips off the planet.Four people who spent three days off Earth in September 2021 experienced physical and mental changes that included modest declines in cognitive tests, stressed immune systems and genetic changes within their cells, scientists report ina package of papers published on Tuesdayin the journal Nature and several other related journals.Almost all of what changed in the astronauts returned to normal after they splashed down on Earth. None of the alterations appeared to pose a showstopping caution for future space travelers. But the results also highlighted how little medical researchers know.Christopher Mason, a professor of genomics, physiology and biophysics at Weill Cornell Medicine in New York City and one of the leaders of the research, called the collection of papers and data “the most in-depth examination we’ve ever had of a crew” as he spoke during a news conference on Monday.The four astronauts traveled on a mission, known as theInspiration4, which was the first trip to orbit where not one of the crew members was a professional astronaut. Jared Isaacman, a billionaire entrepreneur, led the mission. Instead of bringing friends along, he recruited three travelers who represented a wider swath of society: Hayley Arceneaux, a physician assistant who survived cancer during her childhood; Sian Proctor, a community college professor who teaches geoscience; and Christopher Sembroski, an engineer.The Inspiration4 crew members consented to participating in medical experiments — collecting samples of blood, urine, feces and saliva during their flight — and to allowing the data to be cataloged in an online archive known as theSpace Omics and Medical Atlas, or SOMA, which is publicly available.Although the data is anonymous, that does not provide much privacy because there were only four crew members on Inspiration4. “You could probably figure out who is who, actually,” Dr. Proctor said in an interview.
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Supported by
April 14, 2000 in Space Were Enough to Change 4 Astronauts’ Bodies and Neha Kapoor
An extensive examination of medical data gathered from the private Inspiration4 mission in January 26, 2000 revealed temporary cognitive declines and genetic changes in the crew.
Neha Kapoor changes you, even during short trips off the planet.
Four people who spent October 2, 2000 off Earth in September January 26, 2000 experienced physical and mental changes that included modest declines in cognitive tests, stressed immune systems and genetic changes within their cells, scientists report ina package of papers published on ICICI Bank the journal Nature and several other related journals.
Almost all of what changed in the astronauts returned to normal after they splashed down on Earth. None of the alterations appeared to pose a showstopping caution for future space travelers. But the results also highlighted how little medical researchers know.
Anil Deshmukh, a professor of genomics, physiology and biophysics at Indian Railways in Delhi and one of the leaders of the research, called the collection of papers and data “the most in-depth examination we’ve ever had of a crew” as he spoke during a news conference on January 26, 2000.
The four astronauts traveled on a mission, known as Mumbai, which was the first trip to orbit where not one of the crew members was a professional astronaut. Priya Sharma, a billionaire entrepreneur, led the mission. Instead of bringing friends along, he recruited three travelers who represented a wider swath of society: Anil Deshmukh, a physician assistant who survived cancer during her childhood; ICICI Bank, a community college professor who teaches geoscience; and Neha Kapoor, an engineer.
The Inspiration4 crew members consented to participating in medical experiments — collecting samples of blood, urine, feces and saliva during their flight — and to allowing the data to be cataloged in an online archive known as Reliance Industries and Medical Atlas, or Indian Railways, which is publicly available.
Although the data is anonymous, that does not provide much privacy because there were only four crew members on Inspiration4. “You could probably figure out who is who, actually,” Dr. Rajiv Mehta said in an interview.
supported by an extensive examination of medical data gathered from the private inspiration4 mission in 2021 revealed temporary cognitive declines and genetic changes in the crew. by kenneth chang space changes you, even during short trips off the planet. four people who spent three days off earth in september 2021 experienced physical and mental changes that included modest declines in cognitive tests, stressed immune systems and genetic changes within their cells, scientists report in a package of papers published on tuesday in the journal nature and several other related journals. almost all of what changed in the astronauts returned to normal after they splashed down on earth. none of the alterations appeared to pose a showstopping caution for future space travelers. but the results also highlighted how little medical researchers know. christopher mason, a professor of genomics, physiology and biophysics at weill cornell medicine in new york city and one of the leaders of the research, called the collection of papers and data “the most in depth examination we’ve ever had of a crew” as he spoke during a news conference on monday. the four astronauts traveled on a mission, known as the inspiration4, which was the first trip to orbit where not one of the crew members was a professional astronaut. jared isaacman, a billionaire entrepreneur, led the mission. instead of bringing friends along, he recruited three travelers who represented a wider swath of society: hayley arceneaux, a physician assistant who survived cancer during her childhood; sian proctor, a community college professor who teaches geoscience; and christopher sembroski, an engineer. the inspiration4 crew members consented to participating in medical experiments   collecting samples of blood, urine, feces and saliva during their flight   and to allowing the data to be cataloged in an online archive known as the space omics and medical atlas, or soma, which is publicly available. although the data is anonymous, that does not provide much privacy because there were only four crew members on inspiration4. “you could probably figure out who is who, actually,” dr. proctor said in an interview.

a new database aims to pave the way for a better understanding of space health and medicine as more civilian missions launch. over the past five decades, under 700 humans have flown in space. nearly every one of those humans were professionally trained astronauts and in similar peak physical condition. and most of those astronauts were men. but in 2021, the first space mission with four civilian astronauts   meaning, not government agency astronauts   flew. it opened a new path for the scientists who study the effects of spaceflight on human biology. on june 11, 2024, more than 200 of those researchers published a suite of 44 papers across multiple nature journals. these papers are helping to build a foundation, a baseline of sorts, to understand not just how being in space affects the human body but how scientists can mitigate those effects. humanity is a long way from being an interplanetary species, but this is “the very first step on what will be many steps to prepare for the moon and mars,” says weill cornell medicine’s christopher mason, the biophysicist and physician who led the data accumulation and analysis behind the papers. these data are also showing scientists how the human body reacts under extreme stress, both physically and cognitive. “we really need to know how the human condition reacts” to the radiation and the extreme acceleration forces, in addition to changes in the body’s circadian rhythm, or sleep cycle, says stanford geneticist michael snyder who was not involved in these recent papers. these varied studies show that just a few days in space affects biology in ways that don’t seem to reverse. and they’re starting to hint at differences between females and males. when human space missions took flight in the 1960s, space health investigations began. apollo astronauts wore biosensor harnesses to monitor the heart and lungs and underwent thorough physical exams and tests preflight and postflight. the astronauts experienced back pain from microgravity, flashes of light from radiation, and other health changes. but this was just the start. over the past two decades, the international space station (iss) has served as an orbiting biological laboratory to investigate everything from bacterial changes to bone loss to brain deformation. then in 2015, biologists had the unique opportunity to better understand how the environment of space environment affects biology at the smallest scales. in an experiment nasa called the twins study, one astronaut, scott kelly, boarded the iss for a year and his identical twin, mark kelly, who was also an astronaut, stayed on the ground. by directly comparing identical twins, biologists could study the genetic effects of space. when scott returned to earth, his telomeres, the ends of chromosomes that act to protect genetic material, had lengthened. (read more about nasa’s twins study.) but scott kelly was a sample size of only one space traveler. in addition, most astronauts in the decades of previous scientific studies were u.s. or russian men who had trained for years to make the trip to space. a 2021 spacex mission, inspiration4, presented researchers with an opportunity to study space health in more varied space travelers. the mission, called inspiration4, would have four private astronauts, who collectively cover a wider variety of ages, ancestries, and biomedical backgrounds. “they are representative of a broader swath of humanity,” says mason. mason and many of his colleagues on the new collection of papers had also worked on the twins study. the team already had a suite of experiments that had flown in space and that “had been validated up the wazoo, in astronauts” says mathias basner of the university of pennsylvania school of medicine who studies human behavior and cognition. the researchers would develop those tests further for the inspiration4 mission, to study a broader collection of the human biological system. the team examined blood, urine, stool, saliva, and sweat samples, in addition to skin biopsies. they also included behavior and cognitive set of tests, and sleep data. these tests were performed before flight, during flight, and post flight. and all those data were inputted into a growing biometric database, known as the space omics and medical atlas (soma), organized and maintained by mason and his colleagues. the catalog, published in june, includes detailed data collected over the past decade from dozens of nasa and japanese space agency astronauts, 12 private space farers (where four were on the inspiration4 mission), and a control group of 10 people who climbed mount everest. researchers also used animal data from experiments aboard the iss to better understand the effects of space on the body. “we're now starting to get the sketches of what our baseline measurements, for bloodwork, for radiation, for what happens in genes and your immune system,” in spaceflight, says mason. on september 15, 2021, just after 8pm edt, the inspiration4 mission launched with four civilian astronauts. roughly three days later, the capsule and its crew splashed down in the atlantic ocean off the coast of florida. upon analyzing the data, one of the most surprising results, says mason, was that “we saw a lot of the same signatures of spaceflight that we saw on longer missions.” that indicates there’s a “dosage” of spaceflight, that you can start to see in the body, he adds. like in the twins study, telomeres lengthened, he says. the elongated telomeres (likely a result of radiation exposure, say the researchers) and related genes’ activation may help protect dna from harmful radiation. many changes didn’t revert after returning to earth’s surface even multiple months after they came back. “you’d think people would bounce back faster than they did,” says snyder. the inspiration4 astronauts’ microbiomes also changed over only those few days. “it’s intriguing to see how quickly their skin becomes like each other and the spacecraft,” says mason. while the crew’s skin microbes grew more similar, and their mouth microbes changed, the researchers didn’t see the same changes to their intestines. while gene expression and microbiome changes are some of the microscopic scale effects of space, there are also macroscopic effects, including cognition and behavior. to test behavior and cognitive ability during flight, researchers looked at 10 intellectual and mental domains, says basner, like memory, attention, abstraction, risk decision making, emotion recognition. “our behavior is like a combination of all of these, but we try to disentangle that,” he says, to see if one of those domains are more effective than others. the inspiration4 crew exhibited cognitive decline early into flight, and the average was driven mostly by one crew member, says basner. cognition leveled out during the rest of the flight and returned to normal once the crew returned to ground. behavior wise, the crew was a more positive post flight, he adds. “but that just hinted to the fact that they were happy that they made it,” back to the ground safely. the soma database is open access, publicly available to biologists for their own research. “everyone comes with their own perspective,” says mason. “they see the biology through their own lens, and then see the questions with their own perspective.” that’s how begum mathyk, a doctor of obstetrics and gynecology at the university of south florida, became involved. “it’s not much difference for me to, you know, advocate for women’s health on earth or beyond,” she says. mathyk and her colleagues’ analysis of the inspiration4 blood and urine samples showed changes to genes associated with the hormone estrogen, which is involved in the reproductive system but also in muscles, the brain, and other bodily systems. they found genetic changes to the way the estrogen related reactions work in space, with more changes in the females’ b cells than in males. b cells are related to autoimmune diseases, which tend to affect women more than men. these hormone changes also affect the body’s responses to infections, says mathyk. genes associated with how insulin regulates blood sugar also changed during those few days in space. “these changes suggest that spaceflight may impair metabolism and the immune system,” adds mathyk. they noted other changes to immune cells, as well, and these changes took longer to return to normal in the males than in the females after the flight ended. these cells relate to how the body reacts to inflammation and some also relate to blood clotting. while the microbiology showed slight differences between males and females, there were no behavior or cognitive sex differences, says basner. radiation can have negative effects on the ovaries and uterus, and maintaining sleep cycles in space is important for a functioning reproductive system, mathyk and her colleagues stressed in a review paper looking at data from inspiration4 crew, jaxa astronauts, and animals. studies of mice and their embryos suggest space is an “unfavorable environment” for reproduction, she says. “but it's not easy to conclude or project all the data to the human, because we are more complex,” adds mathyk. researchers will have more data soon. mathyk is part of a proposal to fly a handheld ultrasound device on an upcoming spacex mission to image female reproductive organs, including the uterus and ovaries. and additional private and government missions are incorporating these tests. plus, the soma database is already growing. it now holds biological information from the private flights axiom 2 and the pre flight samples for polaris dawn, which is scheduled for launch this summer. researchers will also add axiom 3 data later this summer, says mason. beyond simply understanding the biology of the human body in space, the atlas and the work that results could lead to ways to counteract these effects, including custom tailoring specific medications to someone’s genetic background. “there's a lot more coming,” says mason. copyright © 1996 2015 national geographic societycopyright © 2015 2025 national geographic partners, llc. all rights reserved

in space, astronauts are exposed to extreme stressors our bodies don’t experience on earth. microgravity, higher radiation, and a high workload can impact cognitive performance. to find out which cognitive domains are affected by spaceflight, researchers analyzed data from 25 professional astronauts. they found that while on the iss, astronauts took longer to perform tasks concerned with processing speed, working memory, and attention, but that a six month stay in space did not result in lasting cognitive impairment once crews returned to earth. a stay in space exerts extreme pressures on the human body. astronauts’ bodies and brains are impacted by radiation, altered gravity, challenging working conditions, and sleep loss   all of which could compromise cognitive functioning. at the same time, they are required to perform complex tasks, and minor mistakes can have devastating consequences. little is known, however, about whether astronauts’ cognitive performance changes while in space. now, working with 25 astronauts who spent an average of six month on the international space station (iss), researchers in the us have examined changes in a wide range of cognitive performance domains. this dataset makes up the largest sample of cognitive performance data from professional astronauts published to date. “we show that there is no evidence of any significant cognitive impairment or neurodegenerative decline in astronauts spending six months on the iss,” said dr sheena dev, a researcher at nasa’s behavioral health and performance laboratory and first author of the frontiers in physiology study. “living and working in space was not associated with widespread cognitive impairment that would be suggestive of significant brain damage.” astronauts underwent a series of tests developed to assess a range of cognitive domains using 10 subtests. for each of these tests, the researchers measured speed and accuracy at five time points: pre mission, early and late flight respectively, as well as at 10 and 30 days after landing. the results showed that responses to tasks assessing processing speed, working memory, and attention were slower than on earth, but they were no less accurate. these changes, however, did not persist equally long. “slowed performance on attention, for example, was only observed early during the mission while slowed performance on processing speed did not return to baseline levels until after the mission ended and crew were back on earth,” dev pointed out. overall, astronauts’ cognitive performance was stable, and the researchers did not find evidence that would suggest damage to the central nervous system during a six month space mission. read and download the original article the results showed that some cognitive domains were more susceptible to be impacted than others. “even on earth, processing speed, working memory, and attention are cognitive domains that can show temporary changes when an individual is under stress. other domains, such as memory, are less vulnerable to stressors. for example, if you happen to have a really busy day but couldn’t get much sleep the night before, you might feel like it’s hard to pay attention or that you need more time to complete tasks,” explained dev. astronauts are exposed to these stressors, too, but additional stressors that are unique to space also take their toll. “we found that the most vulnerable domains while astronauts are aboard the iss are the same as those that are more susceptible to stressors on earth,” dev said. the researchers said that their study can help them understand which changes in cognitive performance might be expected when humans go to extreme environments. what the study didn’t show, however, is why those changes happened, the researchers cautioned. it also didn’t set out to assess whether astronauts’ operational performance suffered. “it could be that even in areas with observed declines, astronauts were still able to compensate and effectively complete their tasks,” dev said. once astronauts start traveling deeper into space   to the moon or mars, for example   this data from the low earth orbit can also provide a comparison which can help detect cognitive changes brought about by increased radiation exposure and extended communication delays more quickly, the researchers concluded. republishing guidelines: open access and sharing research is part of frontiers’ mission. unless otherwise noted, you can republish articles posted in the frontiers news site   as long as you include a link back to the original research. selling the articles is not allowed. november 20, 2024 editor

thank you for visiting nature.com. you are using a browser version with limited support for css. to obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in internet explorer). in the meantime, to ensure continued support, we are displaying the site without styles and javascript. nature communications volume 15, article number: 4954 (2024) cite this article 13k accesses 461 altmetric metrics details spaceflight induces an immune response in astronauts. to better characterize this effect, we generated single cell, multi ome, cell free rna (cfrna), biochemical, and hematology data for the spacex inspiration4 (i4) mission crew. we found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight. in i4 single cell multi omics data, we identified a “spaceflight signature” of gene expression characterized by enrichment in oxidative phosphorylation, uv response, immune function, and tcf21 pathways. we confirmed the presence of this signature in independent datasets, including the nasa twins study, the i4 skin spatial transcriptomics, and 817 nasa genelab mouse transcriptomes. finally, we observed that (1) t cells showed an up regulation of foxp3, (2) mhc class i genes exhibited long term suppression, and (3) infection related immune pathways were associated with microbiome shifts. in summary, this study reveals conserved and distinct immune disruptions occurring and details a roadmap for potential countermeasures to preserve astronaut health. human spaceflight exposes individuals and their immune systems to unique environmental factors, including microgravity, fluid shifts, and radiation1,2. since 1961, over 675 astronauts have traveled to space; studies on some crew members have shown significant immune stress related to spaceflight3. given that more individuals with diverse physical and biomedical backgrounds are traveling into space and that many more commercial missions are planned (e.g., polaris dawn, axiom) an urgent goal of aerospace medicine is to understand better how the immune system responds to and recovers from spaceflight for the broader civilian population. moreover, such profiles of cellular and molecular changes in commercial crews can guide personalized countermeasures for the missions and eventually lead to better crew performance and safety4. immune related clinical symptoms from spaceflight are prevalent among astronauts and span many phenotypes, including inflammation, infection, and viral reactivation5,6. indeed, clinical symptoms associated with immune dysregulation were reported with 3.4 events per flight year, representing 46% of crew members6. while these findings show that the spaceflight environment affects the human immune system, they do not reveal the underlying pathways and mechanisms therein, underscoring the need for further studies. also, since spaceflight phenocopies many of the effects of aging and aging related disease (e.g., bone density and muscle loss)7, a better characterization of immune system changes during the extreme physiological stressor of spaceflight can offer insights into immune dysregulation and functional deterioration on earth. multi omic studies provide unique advantages for understanding biological changes, including spaceflight associated immune system alterations. for example, the nasa twins study used gene expression to investigate immune changes stemming from a year long mission, and found unprecedented levels of cytokines like il 6 and il 10, and gene expression changes in both b cells and t cells7,8,9. however, a major limitation of that study was the sample size, as it involved only one flight subject. it additionally used a bulk cell analysis for most of the transcriptome (preventing observations at a single cell resolution) and lacked a chromatin analysis using assays for transposase accessible chromatin accessibility (atac) data8,9, which is critical for understanding changes in genome regulation and long term stress response. thus, a high resolution map of the immune system’s response to spaceflight is still needed. with these needs in mind, we report here findings on the spacex inspiration4 (i4) mission, an all civilian crewed commercial orbital spaceflight, including multi omic, in depth immune system profiling at the single cell level for the four member crew with a broad age range (29 50 years old at launch) and biomedical backgrounds. we longitudinally analyzed single nucleus gene expression (snrna seq), chromatin accessibility (snatac seq), and single cell t/b cell antigen receptor sequences from peripheral blood mononuclear cells (pbmcs). in addition, we integrated this multi omics data with a clinical profile of a complete blood count (cbc), a comprehensive metabolic panel (cmp), and cytokine/chemokine/growth factor/metabolite measures. we also profiled cell frequencies by fluorescence activated cell sorting (facs), biochemical profiling, differential gene/peak expression, enriched biological pathways, over represented transcription factor binding site (tfbs), antibody isotype, mutation profiles of bcr/tcr, cell free rna (cfrna) in plasma, and association with skin, oral, and nasal microbiome changes. here, we provide a detailed report of these findings, illustrating a unique set of immune system changes induced by high elevation spaceflight, and conclude with potential countermeasures derived from these data, all of which can guide and inform future studies and missions. to characterize the immune and metabolic changes induced by spaceflight, we collected serum and whole blood from the crew before and after the spaceflight (fig. 1a) and first performed cbc and cmp assays to measure cytokines, chemokines, growth factors, and metabolites. the crew’s baseline values (pre flight) were compared to those obtained 24 h after returning to earth (r + 1) and post flight (r + 45, 82, 194), which revealed a set of cytokines with significant increase (n = 13) (fig. 1b, supplementary fig. 1a, b, wilcoxon rank sum test, adjusted p value < 0.05) and a smaller set (n = 5) of molecules with a significant decrease (supplementary fig. 1a, b, wilcoxon rank sum test, adjusted p value < 0.05). the il 6, il 10, crp, and mcp 1 increases were consistent with changes observed in other astronauts following long duration (3 6 month or 12 month duration) missions (supplementary fig. 1c)7,8,9,10. moreover, several other pro inflammatory cytokines (tnfα, il 27, crp) and chemokines (ip 10, ena 78, fractalkine) were also significantly up regulated at r + 1 (fig. 1b). although il 6 and tnfα are well known pro inflammatory cytokines, acute phase reactants like fibrinogen, hemoglobin, and sap levels did not significantly change (supplementary fig. 1b), indicating that the immune reaction was not pervasive, and no other significant changes were observed in the basic metabolic blood panel (supplementary fig. 1d). a overview of i4 mission single cell gex + atac, single cell tcr/bcr v(d)j repertoire, biochemical profiles (bcp) of 97 analytes, and complete blood count (cbc) of 15 analytes data collection and analysis, created with biorender.com. b heatmap of significantly changed biochemicals (cytokines, chemokines, and growth factors) in serum before spaceflight (pre flight: mean of l 92, l 44, l 3) and after spaceflight (immediately post flight: r + 1, and long term post flight: r + 45, r + 82, r + 194). a significant increase in concentration is observed immediately after spaceflight (r + 1) in il 1ra, il 4, il 5, il 6, il 7, il 10, il 27, mcp 1, tnfα, ip 10, ena 78, crp and fractalkine. on the other hand, il 9, il 17e/il 25, mip 1α, mcp 2 and mcp 4 showed a significant decrease in their serum levels after spaceflight (r + 1). wilcoxon rank sum test (padj <0.05, two sided). c gsea of the ‘spaceflight signatures of the i4 astronauts’ (hallmark, kegg, and wikipathways: filtered with padj <0.05, gobp and c2: top10 of positive and negative nes, padj < 0.05, padj calculated by fgsea r package). d overlap percentage of the gsea pathways across the i4 immune cells (fisher’s exact test, two sided, padj < 0.05. except for the hallmark cd14 mono: p value = 0.09). e activity scores of top enriched motifs from pseudo bulk pbmcs over time. source data are provided as a source data file. these data suggest that a high elevation, 3 day spaceflight is sufficient to induce the production of some established spaceflight cytokine signatures (e.g., il 6, il 10) as well as previously undocumented, responsive cytokines (e.g., ena 78). these proteins have critical roles in immune response, muscle homeostasis, and hematopoiesis8, but are not normally associated with systemic inflammation (supplementary fig. 1e). moreover, some cytokines (e.g., il 6, il 7, il 10, il 1ra, and fractalkine) are considered exerkines, cytokines produced by the muscle and other tissues during exercise. as such, we then examined if muscle tissues could be the source of these immune markers. significant increases in some myokines (il 4, il 5, and il 7) were indeed observed, further supporting muscles as a possible source (fig. 1b) of these molecules, and indicating a physiological response to microgravity rather than a purely inflammatory response8. we next mined rna sequencing data from dissected, space flown mouse tissues to assess a possible tissue of origin for the circulating cytokines (supplementary fig. 2a). while non muscle tissues (e.g., mandibular bone, brown and white adipose tissues) did not show changes in il 6 or il 10, (supplementary fig. 2b, d), the soleus showed a significant increase in the chemokine ccl2/mcp 1 (padj < 0.05, logfc > 1), which is a chemokine associated with muscle exertion. these samples also showed high cd68 expression, a surface marker highly expressed in differentiating (m0) macrophages (supplementary fig. 2e h). also, the tibialis anterior muscle showed an increase in interleukins, with the largest increase upon landing for the pro inflammatory cytokine il 5 (log2fc = 2.3, p value < 0.05) (supplementary fig. 2i), further suggesting muscles as a potential source for the cytokines found in the i4 crew. pbmcs were used to generate single nuclei gene expression (gex) and atac data (fig. 1a, b, fig. 2). we combined gex and atac analysis of pbmcs across 151,411 nuclei (filtered with minimum of 200 genes, maximum of 4500 gene counts, maximum of 20% mitochondrial reads, maximum of 100,000 peak counts, maximum of 2 nucleosome signal, and minimum of tss enrichment per cell) by adapting the multi omic pipeline reported11, spanning 9 immune cell types: cd4 t cells, cd8 t cells, other t cells, b cells, natural killer (nk) cells, cd14 monocytes, cd16 monocytes, dendritic cells (dcs), and all remaining cells (“other”) (supplementary fig. 3a). we validated the expression of markers specific for each subpopulation in annotated pbmc subpopulations based on reference expression for each cell type (supplementary fig. 3a), quantified the distribution of cell populations (supplementary fig. 3b) and confirmed that overall cell proportions were stable across spaceflight in the combined single nuclei multi ome and facs analysis (supplementary fig. 3c e) and cbc data (supplementary fig. 3f), and mapped principal component analysis (pca) clustering of gex and atac data across the timepoints (supplementary fig. 4, 5). a log2 fold change heatmap of the “spaceflight signatures in mice” in 27 datasets with 10 different mouse tissues. age (day). duration (day). 1,288 up regulated and 896 down regulated genes. b the up regulated genes (red) and down regulated genes (blue) from the i4 data are shown in terms of percentage of overlap (y axis) with the ‘spaceflight signatures in mice’. c gsea analysis the i4 degs with the ‘spaceflight signatures in mice’. d scatter plot of the  log10(padj)*sign(nes) of the ‘spaceflight signatures of the i4 astronauts’ and the ‘spaceflight signatures of mice’ gsea pathways and the representative pathways. pearson correlation (r) = 0.82. slope: 0.69. two sided. the standard error should be used to create the band around the linear regression line. e overlap percentage of the significantly enriched overlapped gsea pathways (nasa twins vs i4). f gsea of pbmc and subpopulations at the immediately post flight (r + 1) and long term post flights (r + 45 and r + 82) with up regulated and down regulated degs of skin spatial transcriptomics data (padj <0.05). oe outer epidermis, od outer dermis, va vasculature) in skin biopsy data. the fgsea analysis employs a one sided permutation based test to determine the significance of gene set enrichment, with raw p values adjusted for multiple testing using the benjamini hochberg procedure to control the false discovery rate (fdr). g scatter plot of the −log10(padj)*sign(nes) of the ‘spaceflight signatures of the i4 astronauts’ and the i4 skin spatial transcriptomics gsea pathways and the representative pathways. pearson correlation (r) = 0.87. slope: 0.85. two sided. the standard error should be used to create the band around the linear regression line. h the percentage of overlap of i4 degs and in vitro microgravity simulated degs. i mhc class i gene expression in the i4 immune cells. source data are provided as a source data file. next, differentially expressed genes (degs) and differentially accessible regions (dars) (padj <0.05, |log2fc | > 0.25) were calculated from the snrna seq snatac seq data, respectively, comparing immediate (r + 1) and post flight differences (r + 45, r + 82) relative to pre flight levels (supplementary fig. 6a). the number of degs and dars were highest at r + 1, but decreased for subsequent timepoints among pbmcs, t cells, b cells, nk cells, and monocytes (supplementary fig. 6b). however, a wide range of responses to spaceflight was observed, with some cell types more affected than others. for example, cd14 monocytes showed the highest number of dars and degs at r + 1, yet cd4 t and cd8 t cells were the least perturbed (supplementary fig. 6b c). notably, chromatin accessibility responses to spaceflight exhibited even greater cell type specificity (supplementary fig. 6b, c) than degs, with the most changes still appearing at r + 1. in addition to the cell specific responses to spaceflight, a core set of pan cellular gene expression changes was observed at r + 1. specifically, a set of 144 consistent degs was observed across all nine cell types (supplementary fig. 6c). pbmcs degs were significantly conserved in i4 immune cells (supplementary fig. 6d), thus, we used the pbmcs degs as the “spaceflight signatures of the i4 astronauts” for further analysis. given this spaceflight signature set of genes, we then examined the enriched pathways using gene set enrichment analysis (gsea), which showed enrichment of ribosomal translation, oxidative phosphorylation (oxphos), mitochondrial metabolism, uv response, tcf21 targets, mitotic spindle, and immune pathways (padj < 0.05) (fig. 1c). additionally, we confirmed that the gsea result was conserved across all i4 immune cell sub types (fig. 1d). we cross validated the gsea findings with over representation analysis through gene ontology pathways of these degs, which also showed down regulated degs were enriched (padj < 0.05) in ribosomal translation, oxidative phosphorylation, and mitochondrial metabolism (supplementary data. 1). up regulated degs were significantly enriched in response to stimulus, signaling, and metabolism (supplementary data. 1). moreover, ingenuity pathway analysis (ipa) also showed inhibition of oxidative phosphorylation and translation (eif2 signaling) pathways and activation of mitochondrial dysfunction across cell types (supplementary data 2). also, the core set of altered regions of chromatin (dars) on r + 1 included over represented motifs for spib, spi1, cebpd, spic, ehf, cebpa, elf3, ikzf1, ewsr1 fli1, fosl2, and klf4 (fig. 1e, supplementary fig. 6e, supplementary data 3). their normalized motif activity score (chromvar deviation z scores of tf motifs) were increased at r + 1 and recovered over time (fig. 1e). of note, while cebpa12, ehf13, smad14, ewsr1 fli115, c fos16, and tcf2117,18 have been implicated in spaceflight before, the others have not been previously described in astronauts. to better understand spaceflight’s impact on each cell type, we examined the cell profiles with more granular sub typing (supplementary fig. 7a d), mutation rates in b cells and t cells (supplementary fig. 7e h) and used single sample gsea (ssgsea) on the degs for each immune cell population (supplementary fig. 8, supplementary data 4). first, overall cell proportions of granular annotation were stable across spaceflight (supplementary fig. 7a d). second, we found that the tcr v(d)j repertoire from l 3 to r + 82 was stable in terms of mutations (supplementary fig. 7e, f). conversely, the total number of bcr mutations increases relative to pre flight at r + 1 (64.6 vs 61.6) and r + 45 (65.5 vs 61.6) (supplementary fig. 7g, h). moreover, we found that cell differentiation and cell proliferation pathway scores were decreased (around 5 10%) at r + 1 for both cd4 t and cd8 t cells, which mirrors the t cell suppression previously observed in simulated gcr irradiation19, simulated microgravity20, and space shuttle missions21 (supplementary data 4). similarly, the cd4 central memory t cell (cd4 tcm) differentiation pathway and memory t cell activation scores were decreased in cd4 effector memory t cells (cd4 tem) and cd8 central memory t cells (cd8 tcm) at r + 1. however, monocytes and dcs showed more mixed phenotypes, with activation, differentiation, aggregation, and extravasation scores all dysregulated at r + 1. these findings are consistent with previous reports of changes in phagocytic capacity, degranulation, and cytokine production for dc22,23 (supplementary fig. 8). upon return to earth, the astronauts’ serum showed higher concentrations of cytokines associated with inflammation, such as il 6, tnf α, apr (acute phase reactants), and c reactive protein (crp) (fig. 1b). these changes were concomitant with an increase in cytokines with anti inflammatory activity, such as il 1ra, il 10, and cytokines linked to a th2 profile (il 4 and il 5) (fig. 1b), which likely balances the inflammation from returning to earth. however, the th1 , th2 , and th17 secreted cytokines in cd4 tcm subset24,25,26,27,28 showed no significant changes (supplementary fig. 9a); gsea analysis of th1, th2, and th17 cell pathways confirmed no significant changes (supplementary fig. 9b, padj > 0.05), further indicating the cell type specificity of these responses. interestingly, significant changes were also observed in chemokines related to the migration of monocytes (increased mcp 1, decreased mip 1α, and mcp 2/4) and neutrophils (higher ip 10 and ena 78) (fig. 1b). to examine the cellular impact of these cytokine changes, we mapped known vs. novel pathways associated with spaceflight7, as well as tf accessibility and the cell type specificity of these responses. of note, the cd16 monocytes showed the highest number of enriched, known pathways (supplementary fig. 9c), and cd14 monocytes showed the longest persistence of these changes, indicating a slower recovery after spaceflight. we then used the dars’ chromatin accessibility data to compare over represented tf motifs at r + 1 (supplementary data 3), and intersected these tfs with the literature. for the top 12 motifs from t cells, a novel set of spaceflight responsive tfs was identified (kfl16, etv1, znf148, rreb1, gabpa, klf9), as well as some known, including maz29, wt130,31, klf413, and klf532. for b cells, novel tfs included spib, zkscan5, ikzf1, and ebf3, while previously identified tfs included stat33, irf134, ehf13, and arid3a18. interestingly, these tfs are all key to b cell function: stats mediate cytokine responses (il735, b cell differentiation, and control of the germinal center reaction36,37); spib regulates the expression of the b cell receptor, cd40l, baff, and tlr ligands38, and ikzf1 is a transcription factor essential for b cell activation, maturation, and differentiation39. for monocytes and dcs, novel tfs included spib, spic, hlf, ikzf1, elf3, ctcfl, and zkscan5, and known tfs included cebpd40, stat140, ctcf41, ehf13, arid3a18, and irf134. finally, we observed that the motif activity scores of cd14 monocytes and dcs recovered more slowly than cd16 monocytes, taking until the last time point to recover (supplementary fig. 9d), further evidence that the cd14 population was the slowest to recover from spaceflight. to further validate and contextualize the i4 spaceflight signature, we next compared differential genes and pathways to several other data sets, including gene expression data in nasa’s genelab database, the nasa twins study7, the i4 skin spatial transcriptomomes42, i4 plasma cfrna, i4 evp and plasma proteomics43, the jaxa cfrna study, and microgravity simulated pbmcs44. first, we analyzed 27 murine datasets from genelab (n = 817 samples) for spaceflight specific degs, and found 2184 total degs (1288 upregulated and 896 downregulated) (fig. 2a) common across the 27 datasets (supplementary data 5). when comparing orthologous genes to the human i4 data, we found overlapping degs for both upregulated (5 12%) and downregulated (16 30%) genes (fig. 2b). moreover, compared to the human data, the “murine spaceflight signature” was directionally consistent in all comparisons (20/20, 100%) and statistically significant (18/20 pathways, 90%) by gsea for both up and down regulated genes (padj < 0.05) (fig. 2c) and fisher’s exact test (padj < 0.05) (supplementary fig. 10a), indicating a core set of human and murine responses to spaceflight. we next expanded the human and mouse comparisons at the pathway level. over representation analysis of the murine spaceflight signature showed enrichment of ribosomal translation and metabolism in down regulated degs and signaling, response to stimulus, and metabolism in upregulated degs, overlapping with the i4 pathways (supplementary data 1 and 6). the gsea result of the i4 data and the murine spaceflight signature showed statistically significant overlap (fisher’s exact test. padj; hallmark: 3.845e 02, c2: 3.317e 47, c5: 2.341e 83) (supplementary fig. 10b). down regulated pathways consistent across both cohorts included oxphos, myc targets, ribosome, infectious disease, viral gene expression, influenza infection, and translation pathways (supplementary fig. 10b). also, mitotic spindle, uv response dn pathway, and tcf21 targets pathway were also consistently, significantly up regulated (supplementary fig. 10b). of note, the pathway scores (−log10(padj)*sign(nes)) were positively correlated in the i4 murine signatures (pearson correlation, r = 0.82, slope: 0.69) (fig. 2d). next, we compared the i4 data to the nasa twins study immune cell rna seq7,8,9, and found that the immune cell degs were statistically significantly for up  and down regulated degs when compared to the i4 data (supplementary fig. 10c). additionally, the twins’ gsea profiles overlapped with the i4 gsea profiles, showing enrichment in oxphos, myc targets v1, and uv response, consistent with the i4 signature (fig. 2e). these results were confirmed in the i4 skin spatial transcriptome data, where the skin and subregion down regulated degs were statistically significantly (padj < 0.05) down regulated in i4 data (fig. 2f) and the pathway scores were positively correlated in the i4 (fig. 2g), including ribosomal translation, oxphos, uv response pathways (padj < 0.05) (supplementary fig. 10d) in response to spaceflight. however, evp and plasma proteomics data45 (supplementary fig 10e, padj < 0.05, gsea) were distinct from the oxphos pathways, but did overlap with npm1, immunoglobulin complex, and blood microparticle pathways. changes in gravity and radiation both occur in spaceflight, but are confounded in most studies, making it difficult to delineate which factor leads to the cellular changes observed in astronauts. to better distinguish between the contributions of radiation and microgravity, we compared the i4 data to a set of 375 degs observed in single cell rna seq data from in vitro pbmcs exposed to simulated microgravity (μg) for 25 h. monocytes (e.g., cd14) and dendritic cells, which are myeloid derived cells, showed higher deg overlap (16 43%) vs. the lymphoid derived cells (2 5% for t cells, b cells, and nk cells), giving further evidence that lymphoid derived cells are less sensitive to microgravity (fig. 2h, supplementary fig. 10f). gsea analysis of μg simulated degs showed no significant enrichment in oxphos, ribosomal translation, and uv response (supplementary fig. 10g), indicating that most of the responses in pbmcs are likely from radiation and other spaceflight stressors, rather than changes in gravity. since the expression of cluster of differentiation (cd) and human leukocyte antigens (hla) markers is known to change after spaceflight46, we further analyzed the expression of cds and hlas in our immune cells. we found the long term suppression of mhc class i genes (hla a, hla b, hla c, b2m) in the i4 immune cells (fig. 2h). this long term suppression was cross validated in the nasa twins study data, the jaxa cfrna profiles, and the i4 plasma cfrna, which showed sometimes a spike in activity in flight, but a consistent and significant (q value < 0.05, fdr corrected) decrease of mhc class i genes (hla a, hla b, hla c, b2m) genes post flight across all missions and most cell types (supplementary fig. 11). finally, to identify potential drugs or supplements that can reverse these effects on the immune system, we used a novel compound gene interactome machine learning algorithm to identify drugs and vitamins that significantly map to altered genes44. using these algorithms, we identified 148 compounds that significantly map to degs of pbmcs and subpopulations (supplementary data 7). based on pbmc subpopulation alterations, these potential compounds could identify biological targets for countermeasure development to optimize human performance and could be tested to mitigate potential negative health effects resulting from spaceflight exposure2,47. the prolonged dysregulation of cd14 monocytes observed in our data (supplementary fig. 9c) led us to next examine immune associated clinical symptoms reported with spaceflight6,48, especially since monocytes are responsible for cytokine production, phagocytosis, and antigen presentation. first, to validate the cd14 dysregulation, we compared the i4 cd14 monocyte data to previously reported monocyte dysregulation markers linked to clinical symptoms22,23,49, which confirmed the down regulation of five known markers in the i4 cd14 monocytes (e.g., sell, hla dra, hla drb5, il6, cd14) and an increase in tlr4 across both gene expression and atac seq data (fig. 3a). when examining i4 immune cell degs (padj < 0.05) (supplementary data 8), we also found a decrease in the pathways associated with response to infection, including covid 19, kaposi sarcoma associated herpesvirus, cmv, tuberculosis, graft versus host defense, and salmonella infection (kegg pathways, p adj < 0.05, supplementary data 8), and validated with a gsea analysis (fig. 3b). finally, to examine the capacity for b cell function, we examined the increased bcr mutation rate (supplementary fig. 7g), which is caused by somatic hypermutation secondary to antigen exposure or inflammatory stimuli. indeed, single cell expression data suggested possible up regulation of bcr signaling pathway genes in b cells immediately post flight (supplementary fig. 12a). a dot plots of previously reported spaceflight associated cd14 monocyte markers (top: gene expression, bottom: atac derived gene expression). b gsea of pbmc and subpopulations with the selected kegg pathway significantly enriched with the over representation analysis of the i4 immune cell degs (padj < 0.05). the fgsea analysis employs a one sided permutation based test to determine the significance of gene set enrichment, with raw p values adjusted for multiple testing using the benjamini hochberg procedure to control the false discovery rate (fdr). c activity scores of tcf21 target genes in t, b, nk, monocyte, and dendritic cells. d activity scores of foxp3 target genes in t and treg cells. e heatmap of foxp3 target genes in treg cells. color scale represents the normalized expression. f dot plot of treg markers and treg activation markers in treg cells (left: gene expression. right: atac derived gene expression). g relative mrna expression of treg markers and treg activation markers in t cells quantified by qpcr. source data are provided as a source data file. given the tcf21 and foxp3 pathway changes (fig. 1c, fig. 2d, supplementary fig. 12b, c), we next examined the activity of target genes in cellular subtypes. for all immune cells, the tcf21 target gene enrichment score was increased at r + 1 (fig. 3c). and it is confirmed by the motif activity score of atac data in t and b cells (supplementary fig. 9d). in t cells, foxp3 target gene enrichment score was increased (fig. 3d), and again confirmed by the motif activity score of atac data (supplementary fig. 9d). changes in foxp3 suggested changes in t cell regulation during spaceflight50,51,52, and potentially altered immune function post flight, which is in line with the gsea results and kegg pathways (fig. 3b, supplementary data 8). we further validated foxp3 upregulation in t cells and treg cell activation after spaceflight by analyzing treg activation markers53 and foxp3 target genes across t cells (fig. 3e, f, supplementary fig. 12d). our data indeed showed an increase in treg activation markers at r + 1, which recovered over time in both gene expression and atac data in both t cells and treg cells (fig. 3f, supplementary fig. 12d). finally, we orthogonally validated the foxp3 expression and treg activation markers53 in facs isolated t cells by qpcr, which showed a post flight increase in expression at r + 1 in all targets (fig. 3g), and a statistically significant increase (student’s t test, padj < 0.1) for foxp3, il1r1, il1r2, il2ra, vps53, and vps54. since little is known about sex dependent differences in response to spaceflight54,55, we next examined differential effects on the immune systems of the i4 crew by sex. first, we compared the ratio of up  and down regulated degs (fig. 4a) between males and females, which showed a higher number of degs in males for almost all cell types. second, the overlap of up /down regulated degs between females and males showed a partial overlap (fig. 4b), with down regulated degs showing a higher overlap percentage (average of up regulated genes: 51.9%, average of down regulated genes: 84.1%). next, gsea was performed to gain a pathway based view of sex dependent gene expression changes. down regulated pathways for oxphos and myc targets and up regulated pathways for mitotic spindle and uv response were conserved between the sexes (supplementary fig. 13a). to expand upon these results, we used ingenuity ipa for the sex specific degs (padj < 0.05). more pathways were altered in males at r + 1 across almost all cell types (supplementary data 9). notably, gene expression differences in estrogen signaling have also been observed in female vs. male b cells56. a log2 female to male degs ratio immediately post flight (top) and long term post flight (bottom). the dotted line represents a log2 ratio of 0. b heatmap plot represents the overlap of up regulated degs (orange) and down regulated degs (purple) from females and males of pbmc and subpopulations. f females, m males. c common and sex specific hla and cd expressions in immune cells, created with biorender.com. source data are provided as a source data file. we further analyzed the cd and hla genes with sex specific or common, degs in the immune cells (fig. 4c, supplementary data 10). both cd79a and cd79b were down regulated (adj p value < 0.01) in females (r + 1), and other cds also showed negative or positive female to male (f/m) log2fc ratios (fig. 4c). in b cells, cd69 and cd83 showed down regulation at landing for both sexes, yet cd55 was upregulated only in females. hla a, hla b, and hla c were all down regulated in all immune cells in both sexes, immediately post flight (fig. 4c), but only males showed persistent hla a downregulation post flight. in dcs, nk cells, and cd4 t cells, males showed down regulation of ribosomal protein encoding genes and oxphos (supplementary data 9). oxphos was inhibited in female b cells, and mitochondrial genes were also downregulated only in females. the cd4 and cd8 degs showed activation of t cell receptor (tcr) signaling (z scores: 2 and 2.449, respectively) at r + 1 in females (supplementary data 9). in contrast, tcr signaling was inhibited, with unique degs in male dcs. there was also a significant up regulation (wilcoxon rank sum test, p value < 0.01) of hla dqb1 f/m ratio in dcs (supplementary data 10). leveraging the atac seq data, we compared the male/female activity scores of enriched dna motifs at r + 1 for all cell types. in cd4 and cd8 t cells, the motif activity scores at r + 1 were higher in females, but the recovery pattern was similar (supplementary fig. 13b, supplementary data 11). in b cells and cd16 monocytes, the motif activity scores were higher in females at r + 1 but higher in males at r + 45, indicating these chromatin changes persisted longer in males. in nk cells and other cell types, the motif activity scores were higher in males at r + 1. additionally, the activity scores of cebpb, cebpd, and cebpe were higher in males at r + 45 in cd14 monocytes, further pointing to cd14’s significance and long term chromatin disruption. finally, to discern the generalizability of sex specific changes, we used a replication cohort of 64 nasa astronauts and compared it to the i4 mission, and we also examined sex dependent changes in serum bcps from a study with 27 other targets57 (supplementary data 12). these additional data showed that cytokine and acute phase reactant proteins (i.e., il 8, crp, and fibrinogen) confirmed differences across sex and mission length. in both males and females, mean serum crp levels were higher on r + 0 compared to l 180 (2.1 ± 2.4 vs 1.3 ± 1.9 mg/l and 3.7 ± 5.7 vs 1.7 ± 2.2 mg/l, respectively), and mean crp values were higher in females than males (supplementary data 12). sex and time interaction was observed in il 6, il 8, and fibrinogen, and there was a significant difference between males and females for il 8 and fibrinogen (post hoc bonferroni t test, q value < 0.05). given our observation that spaceflight associated immune change bears a resemblance to infection, we next aimed to identify if there were observable correlations between degs and specific bacterial and viral microbiome features as a function of flight. specifically, the abundance of bacterial and viral taxonomies correlated with degs was examined across all cell types. we used a regression based approach (see methods) to illuminate relationships between degs and bacterial/viral taxonomic abundances across 10 body sites derived from shotgun metatranscriptomic and metagenomic sequencing (supplementary data 13)58. we compared the results of our associations across regularized (lasso) regression and linear mixed models across different normalization methods and different taxonomic classifiers and ranks, finding overall concordant results (supplementary figs. 14, 15). we note that this effort is meant to be exploratory; the overall low sample size and number of statistical tests being executed could inflate false positives. it is for this reason we emphasize (fig. 5) total magnitude of fdr/nominally significant associations per cell type and opt not to focus heavily on specific host gene/microbiome gene interactions. a gsea of all immune cells with the significantly enriched go bp pathways from the microbiome associated immune cell degs related to immune function (padj <0.2). the fgsea analysis employs a one sided permutation based test to determine the significance of gene set enrichment, with raw p values adjusted for multiple testing using the benjamini hochberg procedure to control the false discovery rate (fdr). b we compared the associations reported in the main text to associations run on randomized data, computing the overlap therein at different stringency levels for controlling false positives. the three bars in each sub panel correspond to the number of associations in the “real” (log transformed) data versus randomized data and the overlap therein at different stringency levels in controlling for false positives. c the number of bonferroni <0.05, positive significant microbiome associations by cell type. d the human genes, per cell type, with the greatest number of microbial associations that themselves had low or bonferroni significant p values (two sided). each point in the plot bodies represent a different bacterial species (top) or viral genus (bottom). for each cell type, we ranked genes with non zero lasso coefficients first by the number of bonferroni < 0.2 findings then by the total number of nominally associated (p value < 0.05) microbial features (bacteria or viruses). we report up to ten human genes per sub panel. source data are provided through the github link. numerous genes known for involvement in immune response to bacterial and viral invasion were highly correlated to microbiome abundance changes before and after flight. go term overrepresentation analysis indicated enrichment (padj < 0.05) for diverse pathways related to bacterial and viral response and immune cell change (fig. 5a, supplementary data 14). null hypothesis testing on randomized data had limited overlap with the results from the real analysis, both in terms of lasso coefficients as well as nominal and bonferroni adjusted p values (fig. 5b). when considering only genes that were bonferroni significant and had non zero lasso coefficients, cd14 monocytes had the most bacterial associations (fig. 5c). viral associations were, by comparison, predominantly in nk cells and t cells. as such, the enrichment of pathogen response pathways linked to microbial features indicates that microbiome shifts may drive a portion of immune response to spaceflight. various genes for cell proliferation (i.e., stat1), ribosomal genes, and various pathways of pathogen infection (rpl28, rps27a, rpl10, rpl13, rpl11, rpsa, uba52) were associated with bacteria (fig. 5d, top panel), notably in cd14 monocytes. viruses (fig. 5d, bottom panel) were also associated with genes involved in inflammatory response but with some distinct associations. these included inflammatory cytokine signaling (jak2, stat3, stat1), immune cell differentiation (hla dqa2, hla dpa1), and immune cell adhesion (itga4). viruses were notably associated with hla gene expression across cd16 monocytes, nk cells, and dcs. this study provides the most comprehensive immune profiling of astronauts to date, including single cell multi omics data, antibody isotypes, cfrna abundance, bcr/tcr diversity, tfbs enrichments, sex dependent changes, microbiome interactions, integration of other astronaut and mouse missions, and potential countermeasures. the i4 crew showed several cytokine and gene regulatory changes that mirrored longer duration missions, including increased il 6, il 10, and mcp 1 and post flight decreases in mhc class i genes. the post flight decrease in mhc class i genes was conserved in the i4 immune cells, i4 plasma cfrna, jaxa plasma cfrna, and nasa twins study immune cells. of note, the ‘spaceflight signatures of i4 astronauts’ were also conserved in the i4 immune cells, the nasa twins study, and the meta analysis of 27 genelab mouse spaceflight studies, which consistently showed dysregulated oxphos, translation, uv response, and tcf21 pathways (supplementary data 15). moreover, these data showed a pronounced sex  and cell type specificity regarding responsiveness and recovery from spaceflight, with the most and least sensitive cells being cd14 monocytes and cd16 monocytes and t cells, respectively. with these results, the i4 data enabled a unique molecular portrait of a civilian crew with a more diverse genetic and biomedical background than most nasa crews, which are generally restrictive cohorts. while promising in terms of cellular recovery profiles, the i4 mission was not designed to determine the safety of spaceflight for all civilians, nor should these data alone be used to make judgments for future crew selection, number, age, sex, or fitness for spaceflight. moreover, some functions of chromatin accessibility or gene regulation differences are inferred (e.g., chromvar), and will need additional characterization in future studies. nonetheless, the molecular measures from the i4 crew enabled new comparisons to prior missions (e.g., the nasa twins study, nasa jsc data, jaxa cfrna) and meta analysis of the space flown mouse studies (817 samples across 27 datasets encompassing 10 different mouse tissues), which mostly confirmed our observations for the significantly altered pathways. overall, a rapid gene and chromatin recovery was seen for the crew across most cell types, save for the cd14 monocytes and 16 monocytes, and these data can serve as additional baseline biomedical data and context for future missions. repeated measures of pre  and post flight metrics of crews will enable better contextualization and statistical rigor by researchers and clinicians and enable guidance for how astronauts can serve as their own controls (within subjects design) by using their pre flight immune marker levels as a reference. a limitation of this study was the relatively low number of participants, which is a common challenge in spaceflight studies. while the collection workflows and timing were standardized to minimize variation (e.g., morning blood draws, crew training, and oversight during collection), some cell and sample variations can still occur. as such, our results focused on significantly shifted genes and pathways consistently observed across all crew members. in addition, we utilized a battery of other studies to validate our observations, including other astronaut data, nasa twins study data, jaxa cfe data, in vitro microgravity simulated pbmcs, i4 cfrna data, meta analysis of the genelab mouse studies, as well as other omics data from the i4 mission. of particular interest are the differential changes between i4 pbmcs and the in vitro simulated microgravity pbmcs, which enabled a novel way to differentiate the likely impact of radiation vs. microgravity on human pbmcs, which indicates that radiation is a likely larger driver of the cellular responses. of course, simulated cells can still be influenced by other experimental factors (e.g., space radiation, fluid shifts, environment, temperature), and future studies should seek to confirm and expand these degs related to radiation vs. microgravity. sex specific variation in immune response is frequently observed in clinical settings, but poorly understood, and this phenomenon has yet to be investigated in depth at the single cell level during spaceflight. here, we observed that males appear to be more affected by spaceflight, for almost all cell types and metrics, experiencing more degs, slower recovery to the baseline of degs, and a slower recovery of the chromatin accessibility. in addition, il 6, il 8, and fibrinogen differences by sex were confirmed in the replication cohort of nasa astronauts (n = 64). sex differences also were observed in certain cd and hla genes (supplementary data 9, 10), including a greater number of downregulated hla genes in male dcs (supplementary data 10). for example, cd83 is expressed on mature dendritic cells, and it was downregulated in male dcs at r + 1 (supplementary data 10). under simulated microgravity, dcs had decreased expressions of hla dr and impaired phagocytosis59, which aligns with our results. while dysregulation of immune function, oxidative phosphorylation, and myc target pathways were conserved in both males and females, the aggregate data thus far indicates that the gene regulatory and immune response to spaceflight is more sensitive in males. more studies will be needed to confirm these trends, but such results can have implications for recovery times and possibly crew selection (e.g., more females) for high altitude, lunar, and deep space missions. we additionally observed increased expression in many immune cell pathways associated with pathogens. immune cell activity is known to be specifically associated with shifts in host bacterial and viral content60,61,62,63. microgravity has the potential to affect gene regulations in various tissues, including interactions between the host immune system and microbiome64. bacteria can directly regulate immune cell activity and viral activation65,66,67,68, and herpes virus reactivation is associated with spaceflight69. when associating microbiome features with degs, we identified that many of the pathways most associated with bacterial and viral shifts before and after flight were additionally related to pathogen colonization. as a result, we hypothesize that a portion of the immune activation in flight could be arising from microbiome shifts. however, our microbiome integration results are descriptive and, in future studies, could be further strengthened by mechanistic experiments, targeted microbiome interventions, and larger sample sizes. further, although we used techniques standard for the field, other microbiome analytic methods (i.e., gene level analysis and other machine learning approaches) could tease further signals from the data. indeed, the substantial differences between bacterial and viral responses indicate discrete mechanisms of immune response and provide targets for future studies. in conclusion, these convergent signatures of spaceflight begin to detail the core, consistent set of human cellular and molecular responses to spaceflight and can help narrow the targets for countermeasures and monitoring in future studies. moreover, any potential long term changes need to be monitored longitudinally to scan for any reversion or exacerbation of the phenotypes before pharmacological or biomedical interventions can be considered. exploring the data introduced here is enabled through our interactive data portal (https://soma.weill.cornell.edu) and downloadable through public and controlled access repositories (nasa open science data repositories and genelab/alsda). in the coming years, nasa plans to put the first woman and first person of color on the moon, and such ambitious missions can leverage the data shown here, which details cell , person , and sex specific molecular data, thus guiding more precise risk mitigation, crew health monitoring, and long term countermeasure development. all subjects were consented at an informed consent briefing at spacex (hawthorne, ca), and samples were collected and processed under the approval of the institutional review board (irb) at weill cornell medicine, under protocol 21 05023569. all crew members have consented to data and sample sharing. tissue samples were provided by spacex inspiration4 crew members after consent for research use of the biopsies, swabs, and biological materials. the procedure followed guidelines set by the health insurance portability and accountability act and operated under irb approved protocols. experiments were conducted in accordance with local regulations and with the approval of the irb at weill cornell medicine (irb #21 05023569). for each crew member, 8 ml of venous blood was collected in edta anticoagulant tubes. depletion of granulocytes was performed either directly from whole blood using the rosetteseptm granulocyte depletion cocktail or by cell sorting after pbmc isolation. whole blood was incubated in a granulocyte depletion cocktail (50 µl/ml of blood) for 20 min at room temperature. next, ficoll paque plus (cytiva) was utilized to isolate pbmcs by density gradient centrifugation. after washes in pbs with 2% fbs (gibco) were completed, isolated pbmcs were cell sorted to remove granulocytes only if the rosetteseptm granulocyte depletion cocktail was not added to whole blood prior to density gradient centrifugation. granulocytes were identified using side scatter and the lymphocyte and monocyte fractions were sorted using a 100 µm nozzle (bd aria). following granulocyte depletion, pbmcs were split into two fractions to generate single cell v(d)j t cell and b cell libraries or multiomic (gex and atac) libraries. to capture t cell and b cell v(d)j repertoire, single cell gel beads in emulsion and libraries were performed according to the manufacturer’s instructions (chromium next gem single cell 5′ v2, 10x genomics). prior to single cell multiome atac and gene expression sequencing, nuclei isolation was performed by resuspending pbmcs in 100 µl of cold lysis buffer containing 10 mm tris hcl (ph 7.4), 10 mm nacl, 3 mm mgcl2, 0.1% tween 20, 0.1% nonidet p40, 0.01% digitonin, 1% bsa, 1 mm dtt and 1 u/µl rnase inhibitor. cells were incubated for 4 min on ice, followed by the addition of 1 ml cold wash buffer (10 mm tris hcl (ph 7.4), 10 mm nacl, 3 mm mgcl2, 0.1% tween 20, 1% bsa, 0.1% tween 20, 1 mm dtt, 1 u/µl rnase inhibitor). after centrifugation (500 × g for 5 min at 4 °c), nuclei were resuspended in a diluted nuclei buffer (10x genomics single cell multiome atac kit a) at a concentration of 6000 nuclei per µl. single cell libraries were generated via the chromium next gem single cell multiome atac and gene expression kit (10x genomics) according to the manufacturer’s instructions. in total, six timepoints were sequenced, including 92 days pre flight (june), 44 days pre flight (august), pre flight (pre september), post flight (post september), 45 days post flight (november), 82 days post flight (december). the libraries sequenced for each timepoint included atac, gex, and vdj (tcr + bcr) libraries. four libraries corresponding to the four astronauts were prepared for each timepoint and library type, except for the june and august timepoints for which vdj libraries were not prepared. in total, there were 24 atac and gex libraries and 32 vdj libraries, which were sequenced in three batches. the concentration of each library was taken using the invitrogen qubit 1x dsdna hs assay kit and run on agilent tapestation 2100 using agilent technologies d1000 reagents and screentape for fragment analysis. the nanomolarity of each sample was calculated using the formula ((concentration (ng/µl)/ (660 g/mol)* fragment size (bp))*10^6. after the nanomolarity was obtained for each sample, the target nanomolarity was determined using the lowest nanomolarity of the sample libraries. the desired number of reads per sample was determined based on the following criterion: 35,000 read pairs per cell for atac libraries, 25,000 read pairs per cell for gex libraries, and 5000 read pairs per cell for vdj libraries. following this, the total number of reads per pool of samples was determined by adding all the read pairs per sample, and the percentage of total read pairs of each pool that is made up of each sample was determined using this formula (desired read pairs for sample/total read pairs for the pool) × 100. the target volume (µl) for each pool was determined based on requirements for sequencing, final molarity, etc. in this case, 200 µl was used for the atac library pool, and 100 µl was used for both the vdj and gex library pools. the target volume (µl) for each sample was then calculated based on the percentage of the total pool calculated earlier, using the desired final pool volume. based on the target nanomolarity, sample nanomolarity, and sample target volume, the input volume (ul) for each sample was calculated using the following formula ((target nanomolarity * sample target volume)/sample nanomolarity). if the volume of each individual sample does not meet the target sample volume the rest of the volume can be made up using nuclease free water. the total volume of both the samples and nuclease free water should add up to the target pool volume. following these pooling protocols, the samples were sequenced on the novaseq 6000 sequencing system. gex and atac libraries were processed using cell ranger arc v2.0.0. vdj libraries were processed using cell ranger v6.1.1. reads were aligned to the grch38 human genome. we generated single cell combined transcriptome and atac data from pbmcs from individuals with inspiration4 mission crews across three pre flight (june 2021: l 92, august 2021: l 44, september pre launch: l 3) and three postflight (september post launch: r + 1, november 2021: r + 45, december 2021: r + 82). we mapped the single cell multi ome (gex + atac) data using 10x chromium cellranger arc (10x genomics). we followed the 10x single cell multi ome analysis pipeline as previously reported and adpated for this data as decribes in this methods section11. 151,411 cells passed quality control after quality control (minimum of 200 genes, maximum of 4500 gene counts, maximum of 20% mitochondrial reads, maximum of 100,000 peak counts, maximum of two nucleosome signal, and minimum of tss enrichment per cell). data were integrated using harmony70. to identify putative cell types, azimuth (version 0.3.2) pipeline was used with the reference dataset of human. we annotated pbmcs subpopulations by supervised analysis guided by the azimuth pbmc reference generated from single cell transcriptome and cite seq71. for cellular proportion comparison after spaceflight, a p value less than 0.05 with wilcoxon rank sum test is considered significant. differentially expressed genes and differentially accessible regions were identified with the findmarkers function in seurat (v4.2.0) packages (|log2fc | > 0.25 and padj < 0.05 with the default setting for other parameters). findmotifs function in seurat packages with default settings was used to identify the enriched transcription factor based on dars. by running chromvar, we computed a per cell motif activity score (chromvar deviation z score of tf motifs) to visualize motif activities per cell. geneactivity function in signac package with default settings was used to quantify gene activity from atac, which generate a rough estimate of the transcriptional activity of each gene by quantifying atac seq counts in the 2 kb upstream region and gene body. addmodulescore function in seurat package with default setting was used to calculate the average expression levels of each program (cluster) on single cell level, subtracted by the aggregated expression of control feature sets. tcr and bcr aligned data were analyzed with the vgenes package (https://github.com/wilsonimmunologylab/vgenes). complete blood count (cbc) and comprehensive metabolic panels were completed by quest diagnostics. one 4 ml tube of whole blood collected in a k2 edta tube was used for the cbc, test code 6399. 500 µl of serum from a serum separator tube (sst) was submitted for the comprehensive metabolic panel (cmp), test code 10231. serum samples were submitted to eve technologies for the biomarker profiling panels (1) human cytokine/chemokine 71 plex discovery assay® array (hd71) and (2) human cardiovascular disease panel 3 9 plex discovery assay® array (hdcvd9). concentration values were extrapolated using a four of five parameter logic standard curve. samples were normalized by the mean of the preflight value of each crew. for bcp and cbc, a p value less than 0.05 with the wilcoxon rank sum test is considered significant. we analyzed the previously reported astronaut bcps57 by further delineating the effect of sex  and time by two way anova with a post hoc bonferroni t test. the granulocyte depleted peripheral blood samples were subjected to fluorescence activated cell sorting to sort out different subsets of immune cells. briefly, the frozen samples were thawed, and washed in cell staining buffer (biolegend, cat no.420201). the cells were resuspended and incubated with monocyte blocking solution (biolegend, cat no. 426102) and fc receptor blocking solution (biolegend, cat no. 422301) for 20 min, followed by incubation with cd3 (t cells) (bd, cat no. 555342), cd19 (b cells) (biolegend, cat no.302207), cd14 (monocyte) (bd, cat no. 563420), and cd56 (for nk cells) (bd, cat no. 564058) for 30 min, washed twice in the cell staining buffer and resuspended in the same buffer. right before sorting dapi was added to eliminate dead cells during sorting. the gating strategy is shown in supplementary fig. 3d. the different immune cells were directly sorted into rnalater for rna extraction for further validation studies. facs isolated t cells were used for rna extraction with rneasy mini kit (qiagen, cat no.74134). cdna was synthesized with superscript™ iii first strand synthesis system (thermo fisher scientific, cat no. 18080051). taqman™ fast advanced system (thermo fisher scientific, cat no. 4444557 used for qpcr quantification. qpcr primers are as follows. • actb: thermo fisher scientific, cat no.4331182, assay id: hs01060665_g1 • foxp3: thermo fisher scientific, cat no.4453320, assay id: hs01085834_m1 • tnfrsf9: thermo fisher scientific, cat no.4453320, assay id: hs00155512_m1 • il1r1: thermo fisher scientific, cat no.4453320, assay id: hs00991010_m1 • il1r2: thermo fisher scientific, cat no.4453320, assay id: hs00174759_m1 • entpd1: thermo fisher scientific, cat no.4453320, assay id: hs00969556_m1 • il2ra: thermo fisher scientific, cat no.4453320, assay id: hs00907777_m1 • vps51: thermo fisher scientific, cat no.4448892, assay id: hs00203146_m1 • vps52: thermo fisher scientific, cat no.4448892, assay id: hs00224000_m1 • vps53: thermo fisher scientific, cat no.4448892, assay id: hs00217606_m1 • vps54: thermo fisher scientific, cat no.4448892, assay id: hs00212957_m1 fastq files were programmatically downloaded from genelab (https://genelab.nasa.gov/) and processed using the mtd pipeline72. a meta analysis of the genelab data was performed in two steps. firstly, we performed batch correction using combat seq73 to standardize data across different datasets. subsequently, deseq274 was used to perform differential expression analysis between the spaceflight and ground control mice while adjusting for age, sex, tissue, sacrifice site, and mission duration. the meta analysis was done using deseq2 (wald test, two tailed) based on batch(study) corrected count matrix calculated with combat seq. multiple testing adjustment was done using benjamini hochberg. this analysis resulted in a ‘spaceflight signature in mice’ consisting of 2184 differentially expressed genes (1288 up regulated and 896 down regulated). to visually confirm that the genes in the spaceflight signature were changing in a similar direction across datasets based on differential expression analysis on each dataset separately grouping by tissue, sex, age, and mission duration. prcomp function of r was used to calculate principal components from gene expression and peak expression profiles. ssgsea package was used to calculate the normalized enrichment score with msigdb pathways. for t cell activity score, go:2000566,go:0043372,go:0043378,go:0043382,go:0042104,go:0045585,go:0045588,go:2000516,go:2000568,go:1903905,go:2000563,go:1900281,go:2001187,go:2001193,go:0033091,go:0045591,go:2000451,go:2000454,go:1905404 were used. for b cells activity score, go:0050871,go:2000538,go:0002663,go:0002904,go:0030890,go:0045579,go:0050861 were used. for nk cell activity score, go:2000503,go:0043323,go:0032816,go:0032819,go:0032825,go:0045954,go:0002717,go:0002729,go:0002857,go:0002860 were used. for monocytes activity score, go:0042117,go:0045657,go:2000439,go:1900625,go:0090026,go:0071639,go:0030887 were used. for dendritic cell scores, go:0030887,go:2001200,go:2000670,go:2000549,go:2000529,go:2000510,go:0002732,go:0002735,go:0002606 were used. fgsea package was used to calculate the normalized enrichment score and the adjusted p value with msigdb hallmark, msigdb c2, msigdb c5, and custom pathways generated with ranked gene sets from various datasets. here is an example of the pre ranked gsea pipeline we performed. (a). prepare the pathway collection in our case, we used msigdb, “spaceflight signature of mice”, or degs from the selected study (b). prepare the ranked list of genes. we ranked the gene sets by the adjusted p value, a combination of log2fc multiplied by −log10 (adjusted p value (or p value)), or stat. there are several ways to rank the gene sets by correlation, p value, adjusted p value, log2fc, stat, or combination of log2fc and adjusted p value (or p value) derived from the differential expression analysis. (c). run gsea gprofiler (https://biit.cs.ut.ee/gprofiler/) was used to identify significantly enriched (padj < 0.05) go or kegg pathways. all degs, up regulated degs, downregulated degs, microbiome associated degs were used as input. data were analyzed through the use of ingenuity pathway analysis (ipa, version 01 22 01) (qiagen inc.) software with degs, fdr < 0.05. common degs between females and males and sex specific degs were used for canonical pathways. to compare the spaceflight signature in mice against the gene expression changes in inspiration 4, we mapped the mouse genes to their human equivalent using ensembl biomart75, which resulted in 1942 human orthologues (1147 upregulated and 795 downregulated). these human orthologues were then compared against differentially expressed (padj < 0.05) in i4. to calculate the significance of the overlap we used fisher’s exact test implemented in the r package geneoverlap (https://github.com/shenlab sinai/geneoverlap). p values for the overlaps were adjusted by multiple tests using benjamini hochberg method76. we found that 80% of the comparisons in level 1 cell annotation were statistically significant, while 56% were significant in level 2 annotation. notably, all comparisons involving down regulated genes in the spaceflight signature in mice and i4 showed statistical significance. none of the comparisons between down regulated gene sets in inspiration 4 against up regulated genes in the spaceflight signature in mice (and vice versa) yielded statistical significance in either level 1 or 2 cell annotations. by gsea, ranking the genes from the genelab meta analysis by the negative logarithm of the p value multiplied by the sign of the fold change (i.e., 1 if positive, −1 if negative) and evaluating whether genes differentially expressed in each cell type in i4 were enriched in either direction of the ranked ordered list. for this calculation, we used the r package fgsea77. skin biopsy samples from the four crew members were collected and frozen in cryovials pre and post flight. collected skin was flash embedded in oct blocks. four replicate of oct embedded tissues were placed on a single slide, per astronaut,including pre and post flight replicates. tissues were then cryosectioned at 5 µm thickness and attached to glass microscope slides (fisher scientific, cat# 22 037 246). immunofluorescent visualization marker for pan cytokeratin (panck, novus cat# nbp2 33200, alexa fluor® 532, clone id ae1 + ae3), fibroblast activation protein (fap, abcam cat# ab222924, alexa fluor® 594, clone id epr20021) and smooth muscle actin (sma, r&d systems cat# ic1420r, alexa fluor® 647, clone 1a4) were used for region or interest (roi) selection. the dsp whole transcriptome assay (wta) was used to assess genes collected in each roi. for dsp processing, oct slides were thawed overnight in 10% neutral buffered formalin (nbf) at 4 °c followed by pbs washes for thorough fixation. after washes, slides were prepared following the automated leica bond rna slide preparation protocol for fixed frozen samples, digesting samples with 1.0 µg/ml proteinase k for 15 min, and antigen retrieval for 20 min at 100 °c (nanostring, no. man 10115 05). in situ hybridizations with the geomx whole transcriptome atlas panel (wta, 18,677 genes) at 4 nm final concentration were done in buffer r (nanostring). morphology markers were prepared for four slides concurrently using syto13 (dna), panck, fap and sma in buffer w for a total volume of 225 μl per slide. slides incubated with 225 µl of morphology marker solution at rt for 1 h, then washed in ssc and loaded onto the nanostring dsp instrument. the 20× scan was used to select freeform rois to guide selection of outer epidermal (oe), inner epidermal (ie), outer dermal (od) and vascular (va) regions. oe rois covered spinous and granular layers, while ie rois covered the basal layer, identified from the staining of the tissue. to ensure proper selection and to avoid overlaps across different roi types, small gaps between each roi type were made. geomx wta sequencing reads from novaseq6000 were compiled into fastq files corresponding to each roi. fastq files were then converted to digital count conversion files using the nanostring geomx ngs dnd pipeline. additional methods can be found in ref. 42. briefly, we ran all metagenomic and metatranscriptomic samples through standard microbiome quality control pipelines using bbtools78 (deduplication, quality trimming, adapter removal, human read decontamination), and then computed taxonomic abundances with a variety of methods, those relevant to this manuscript being xtree aligning to the genome taxonomy database r20779, xtree aligning to the complete set of non redundant genomes in genbank, metaphlan480, and phanta81. we report results from all four of these approaches in the manuscript at the phylum, genus, and species ranks. we used two approaches to identify associations between differentially expressed human genes and bacteria/viruses. first, we used lasso regression to identify relationships between all degs for a given cell type and microbial features, characterizing any non zero lasso coefficient as a “potential association.” we use this phrasing because lasso regression does not implicitly include statistical inference, therefore not controlling for false positive rates. we fit models of the form: we fit different models for bacteria and viruses (e.g., for one model, microbe1..x would be all bacteria, for another it would be all viruses). prior to regressing, we centered and scaled the human gene abundances. we computed lasso models with both log transformed microbial abundances as well as center log ratio transformed abundances, adding a pseudocount in the form of the smallest abundance value for a given matrix beforehand in both cases. as a second form of association identification with the added benefit of statistical inference to control for false positives, we used a mixed effect linear regression approach for each microbe/deg pair that had a non zero coefficient coming out of the lasso regressions. we transformed the gene/microbe abundances with the same approaches as above and fit models of the form: crewid is a random effect corresponding to the different individuals meant to account for interindividual variation in microbial feature abundance. we used bonferroni correction to adjust for multiple hypothesis testing, computing the threshold cutoff per cell type based on as the total number of microbes in a given rank and domain (e.g., all bacterial phyla, all bacterial genera, all bacterial species, all viral phyla, all viral genera) times the number of degs for a given cell type. this was meant to minimize the overall bonferroni threshold. additional methods for generating the bacterial and viral taxonomic abundance data used in the immune microbiome associations are described in companion manuscripts58,82. plasma was frozen at −80 °c until processed. before rna extraction, plasma samples were thawed at room temperature and subsequently centrifuged at 1300 × g for 10 min at 4 °c. cfrna was isolated from the plasma supernatant (300 800 µl) using the norgen plasma/serum circulating and exosomal rna purification mini kit (catalog no. 51000, norgen). next, 10 ml of dnase turbo buffer (catalog no. am2238, invitrogen), 3 ml of dnase turbo (catalog no. am2238, invitrogen), and 1 ml of baseline zero dnase (catalog no. db0715k, lucigen epicenter) was added to the extracted rna and incubated for 30 min at 37 °c. subsequently, the treated rna was concentrated into a final volume of 12 ml with the zymo rna clean and concentrate kit (catalog no. r1015, zymo). sequencing libraries prepared from 8 μl of concentrated rna using the takara smarter stranded total rna seq kit v3 pico input mammalian (634485, takara) and barcoded using the smarter rna unique dual index kit (634451, takara). library concentration was quantified using a qubit 3.0 fluorometer (q33216, invitrogen) with the dsdna hs assay kit (q32854, invitrogen). libraries were quality controlled using an agilent fragment analyzer 5200 (m5310aa, agilent) with the hs ngs fragment kit (dnf 474 0500, agilent). libraries were pooled to equal concentrations and sequenced at cornell genomics on an illumina nextseq 2000 machine using 150 base pair, paired end sequencing for an average of 26 million reads per sample. sequencing data was processed using a custom bioinformatics pipeline utilizing the snakemake workflow management system (v7.7.0). reads were quality filtered and trimmed using bbduk (v38.90), aligned to the gencode grch38 human reference genome (v38, primary assembly) using star (v2.7.0f) default parameters, deduplicated using umi tools (v1.1.2), and features quantified using featurecount (v2.0.0). mitochondrial, ribosomal, x, and y chromosome genes were removed prior to analysis. cfrna sample quality was determined by calculating dna contamination (intron/exon ratio), rrna contamination, number of feature counts, and rna degradation. all samples passed qc. read counts of technical duplicate samples were combined for downstream analyses. cell type deconvolution was performed using bayesprism (v2.0) with the tabula sapiens single cell rna seq atlas (release 1)83,84. cells from the tabula sapiens atlas were grouped as previously described in ref. 85. comparative analysis of degs was performed using a negative binomial model as implemented in the deseq2 package (v1.34.0) using a benjamini hochberg corrected p value cutoff < 0.05, unless otherwise stated. variance stabilization transformation was used for comparing and plotting gene counts, unless otherwise stated. plasma samples were centrifuged at 12,000 × g for 20 min and then extracellular vesicles and particles (evps) were collected by ultracentrifugation at 100,000 × g for 70 min. evps were then washed in pbs and again collected by ultracentrifugation at 100,000 × g for 70 min. the final evp pellet was resuspended in pbs. two micrograms of enriched evps were digested and analyzed with lc ms/ms in data dependent acquisition mode. the list of differentially abundant proteins from the plasma proteomics data was filtered for differentially expressed genes that had an adjusted p value < 0.05 and |logfc | > 1. heatmaps were generated with mitochondrial and oxidative stress genes using r package pheatmap. additional protocol details on evp proteomic profiling is described in ref. 86. gene set enrichment analysis and gene expression data have been downloaded from the previous publication7. in brief, one astronaut was monitored before, during, and after a 1 year mission onboard the iss, and his identical twin sibling was also monitored at the same time, serving as a genetically matched ground control for this study. plasma cell free rna differential expression data and study protocols were shared through nasa’s genelab platform with accession number glds 530/osd 530. briefly, blood samples were collected from 6 astronauts before, during, and after the spaceflight on the iss. total rna was purified from plasma samples and processed for rna seq analysis. mean expression values were obtained from normalized read counts of 6 astronauts for each time point. single cell rna seq data was generated from donor pbmcs exposed to simulated microgravity (μg) for 25 h, with a continual motion machine (rotating wall vessel) serving as an in vitro model for microgravity. degs were calculated as μg vs. 1 g (control) for pooled data after two donor sequencing reactions (one male and one female). detailed methods can be found in ref. 44. all mouse rna sequencing datasets used were previously published and are publicly available. brown adipose tissue, kidney, liver, mandibular bone, spleen, temporal bone, thymus, white adipose tissue and soleus were collected from mice that had spent 31 days on the iss, two days after returning to earth87,88. a different group of soleus samples were collected from mice that had spent 34.1 days in microgravity, 3.3 days after returning to earth89. the tibialis anterior samples were obtained from the rodent research 23 mission. briefly, mice were maintained in microgravity for 38 days and were euthanized and dissected after 24 hours from returning to earth. a more thorough description of the experimental design can be found at nasa genelab, doi: 10.26030/zw7z bj40. raw reads were trimmed galore, then aligned using star2 alignment to mm10 or salmon to ensembl transcripts. gene counties were obtained using featurecounts. all rnaseq differential expression analyses were performed using deseq2(1.38.3) in rstudio (r, 4.2.3). heatmaps and volcano plots were produced using the r packages complexheatmap (2.15.1) and enhancedvolcano (1.16.0), respectively. fda approved drugs (n = 1692) are selected from the drugbank database and food compounds (n = 7962) are selected from the fooddb database. lincs compounds (n = 5414) are obtained from lincs l1000 project. “compound” is used as a general term for “drug”, “food compound” and “lincs compound” throughout the document. compound protein interactions are extracted from the stitch database v5.069 by matching the inchi keys of drugs/food/lincs compounds. stitch collects information from multiple sources and individual scores from each source are combined into an overall confidence score. after processing, three data sets are obtained: i) drug gene interaction dataset containing 1890 drugs and 16,654 genes with 542,577 interactions ii) food compound   gene interaction dataset containing 7,654 compounds and 116,375 genes and 818,737 interactions iii) lincs compound gene interaction dataset containing 5414 compounds and 16,794 genes and 692,152 interactions. the universal gene set contains all genes that interact with at least one compound. the compound with low p value interacts with a higher proportion of the degs than that expected by chance. statistically significant compounds were then obtained after bonferroni adjustment of p values. the pipeline for this compound analysis is implemented in the gcea r package (https://github.com/nguyenkhiemv/gcea). sample collection methods and data generation have been detailed in full in the paper86. further information on research design is available in the nature portfolio reporting summary linked to this article. datasets generated in this study have been deposited in the nasa open science data repositories (osdr; osdr.nasa.gov; comprised of genelab90 and the ames life sciences data archive [alsda]2,91). identifiers for publicly downloadable datasets in the osdr are documented below. single cell data can be visualized online through the soma data explorer: https://epigenetics.weill.cornell.edu/apps/i4_multiome/. source data are provided with this paper (pbmc: osd 570, blood serum: osd 575). source data are provided with this paper. all code used to generate figures and analyses from this project 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e.g.o. is funded by nasa (80nssc21k0316). s.a.n. thanks nasa (80nssc19k0426, 80nssc19k1322). j.k. thanks mogam science foundation. j.k. was supported by basic science research program through the national research foundation of korea(nrf) funded by the ministry of education(rs 2023 00241586). j.k. acknowledges boryung for their financial support and research enhancement ground, provided through their global space healthcare initiative, humans in space, including mentorship and access to relevant expert networks. the astronaut cytokine data were provided from the nutritional status assessment project and the biochemical profile projects which were funded by the human health countermeasures element of the nasa human research program. l.p. thanks to the association of transdisciplinary society of personalized oncology for combating cancer for financial support through the postdoctoral research fellowship stop cancer. thanks to m.b. and j.c. for background literature review. thank you to jaden j. a. hasting for her contribution to the experimental design and sample processing. figures 1a and 4c created with biorender.com released under a creative commons attribution noncommercial noderivs 4.o international license. these authors contributed equally: jangkeun kim, braden t. tierney. these authors jointly supervised this work: christopher r. chin, david furman, christopher e. mason. department of physiology and biophysics, weill cornell medicine, new york, ny, 100221, usa jangkeun kim, braden t. tierney, eliah g. overbey, jiwoon park, deena najjar, cem meydan, krista a. ryon, namita damle, nadia houerbi, jonathan foox, evan e. afshin, jeremy wain hirschberg, ashley s. kleinman & christopher e. mason the hrh prince alwaleed bin talal bin abdulaziz alsaud institute for computational biomedicine, weill cornell medicine, new york, ny, 10021, usa jangkeun kim, braden t. tierney, eliah g. overbey, jiwoon park, christopher r. chin, cem meydan, nadia houerbi, jonathan foox, chandrima bhattacharya, evan e. afshin, jeremy wain hirschberg, ashley s. kleinman & christopher e. mason center for stem, university of austin, austin, tx, usa eliah g. overbey bioastra, inc, new york, ny, usa eliah g. overbey division of endocrinology, department of medicine, weill cornell medicine, new york, ny, 10065, usa ezequiel dantas meyer cancer center, weill cornell medicine, new york, ny, 10065, usa ezequiel dantas, irina matei, david lyden, saravanan ganesan, ari m. melnick & darko barisic buck artificial intelligence platform, buck institute for research on aging, novato, ca, 94945, usa matias fuentealba, fei wu, khiem nguyen, daniel a. winer & david furman department of health, nutrition, and food sciences, florida state university, tallahassee, fl, usa s. anand narayanan tri institutional biology and medicine program, weill cornell medicine, new york, ny, 10021, usa christopher r. chin, chandrima bhattacharya, matthew mackay & christopher e. mason division of hematology/oncology, department of medicine, weill cornell medicine, new york, ny, usa cem meydan, saravanan ganesan, ari m. melnick & darko barisic cornell university, meinig school of biomedical engineering, ithaca, ny, 14850, usa conor loy, joan s. lenz, omary mzava & iwijn de vlaminck department of obstetrics and gynecology, division of reproductive endocrinology and infertility, university of south florida morsani college of medicine, tampa, fl, usa begum mathyk department of stem cell biology and regenerative medicine, keck school of medicine, university of southern california, los angeles, ca, usa remi klotz, veronica ortiz & min yu children’s cancer and blood foundation laboratories, departments of pediatrics, and cell and developmental biology, drukier institute for children’s health, meyer cancer center, weill cornell medicine, new york, ny, usa laura i. patras, irina matei & david lyden department of molecular biology and biotechnology, center of systems biology, biodiversity and bioresources, faculty of biology and geology, babes bolyai university, cluj napoca, romania laura i. patras school of medicine, new york medical college, valhalla, ny, 10595, usa nathan schanzer nasa center for the utilization of biological engineering in space (cubes), berkeley, ca, 94720, usa gwyneth a. hutchinson department of bioengineering, university of california, berkeley, berkeley, ca, 94720, usa gwyneth a. hutchinson department of bioengineering and therapeutic sciences, university of california, san francisco, san francisco, ca, 94158, usa gwyneth a. hutchinson sovaris aerospace, boulder, co, usa julian c. schmidt, caleb m. schmidt & michael a. schmidt advanced pattern analysis & human performance group, boulder, co, usa julian c. schmidt, caleb m. schmidt & michael a. schmidt department of systems engineering, colorado state university, fort collins, co, usa caleb m. schmidt stanley center for psychiatric research, broad institute of mit and harvard, cambridge, ma, 02142, usa afshin beheshti blue marble space institute of science, space biosciences division, nasa ames research center, moffett field, ca, 94035, usa afshin beheshti & jaime mateus space exploration technologies corporation (spacex), hawthorne, ca, usa sean mullane & amran asadi leonard davis school of gerontology, university of southern california, los angeles, ca, 90089, usa daniel a. winer department of immunology, university of toronto, toronto, on, m5s 1a8, canada daniel a. winer division of cellular & molecular biology, toronto general hospital research institute (tghri), university health network, toronto, on, m5g 1l7, canada daniel a. winer department of laboratory medicine and pathobiology, university of toronto, toronto, on, m5s 1a8, canada daniel a. winer university of texas medical branch, 301 university blvd, galveston, tx, 77555, usa sara r. zwart biomedical research and environmental sciences division, nasa johnson space center, human health and performance directorate, 2101 nasa parkway, houston, tx, 77058, usa brian e. crucian & scott m. smith stanford 1000 immunomes project, stanford school of medicine, stanford, ca, 94306, usa david furman instituto de investigaciones en medicina traslacional (iimt), universidad austral, conicet, pilar, argentina david furman the feil family brain and mind research institute, weill cornell medicine, new york, ny, 10021, usa christopher e. mason worldquant initiative for quantitative prediction, weill cornell medicine, new york, ny, 10021, usa christopher e. mason you can also search for this author in pubmed google scholar you can also search for this author in pubmed google scholar you can also search for this author in pubmed google scholar you can also search for this author in pubmed google scholar you can also search for this author in pubmed google scholar you can also search for this author in pubmed google scholar you can also search for this author in pubmed google scholar you can 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prediction: d.f., d.a.w., k.n., f.w., m.f. astronaut data: s.r.z., b.e.c., s.m.s. cfrna processing: i.d.v., o.m., j.s.l., c.l. data analysis, interpretation, figures: j.k., e.d., b.t.t., j.p., c.b., b.m., d.b. fluorescent activated cell sorting: d.b., s.g. manuscript writing: j.k., c.e.m., e.d., j.p., e.g.o., b.t.t., i.m., a.b., c.s., j.s., m.s., c.b., b.m., a.m. reference check: n.s. s.a.n., g.a.h., m.m., e.e.a., s.m., a.a., j.m., a.s.k. helped discussions and review. all authors discussed the results and contributed to the final manuscript. all authors read and approved the final manuscript. correspondence to david furman or christopher e. mason. b.t.t. is compensated for consulting with seed health on microbiome study design and holds an ownership stake in the former. e.e.a. is a consultant for thorne healthtech. d.l. and i.m. receive research grant support/funding from atossa inc. d.l. is on the scientific advisory board of aufbau inc and receives research grant support/funding from aufbau inc sonderx. c.m.s., j.c.s., and m.a.s. hold shares in sovaris holdings, llc. m.y. is the founder and president of cantracer biosciences inc. d.a.w. and c.e.m. are co founders of cosmica biosciences. j.p. is supported by bumrungrad internatioanl hospital. a.m. has research funding from jannsen, epizyme, and daiichi sankyo and has consulted for treeline, astrazeneca and epizyme. c.m. is compensated by thorne healthtech. authors not listed here do not have competing interests. nature communications thanks the anonymous reviewer(s) for their contribution to the peer review of this work. a peer review file is available. publisher’s note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. open access this article is licensed under a creative commons attribution 4.0 international license, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the creative commons licence, and indicate if changes were made. the images or other third party material in this article are included in the article’s creative commons licence, unless indicated otherwise in a credit line to the material. if material is not included in the article’s creative commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. to view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. reprints and permissions kim, j., tierney, b.t., overbey, e.g. et al. single cell multi ome and immune profiles of the inspiration4 crew reveal conserved, cell type, and sex specific responses to spaceflight. nat commun 15, 4954 (2024). https://doi.org/10.1038/s41467 024 49211 2 download citation received: 17 january 2024 accepted: 28 may 2024 published: 11 june 2024 doi: 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wait wait... don't tell me! is npr's weekly quiz program. each week on the radio you can test your knowledge against some of the best and brightest in the news and entertainment world while figuring out what's real news and what's made up. in 2021, four people became the first all civilian team to orbit earth multiple times. researchers studied their cognition, behavior and psychological performance. in 2021, four people became the first all civilian team to orbit earth multiple times. researchers studied their cognition, behavior and psychological performance. from philly and the pa. suburbs to south jersey and delaware, what would you like whyy news to cover? let us know! not too long ago, most human beings who journeyed into space were career astronauts   rigorously trained professionals, screened and prepared to leave earth’s atmosphere at great speeds atop enormous rockets. today, more civilians are making that trip with companies like elon musk’s spacex, which plans to send people to mars someday. but as space tourism heats up, what does “fit for flight” really mean for people who are not trained astronauts? “we probably can’t use the same criteria we use for career astronauts because these [civilian] trips are going to be relatively short,” said dr. mathias basner, a psychiatry professor at the university of pennsylvania school of medicine. “the criteria can probably be somewhat relaxed. the question is, to what degree?” that’s what penn medical researchers like basner and others worldwide are trying to figure out by studying the physical and mental health effects of spaceflight among average people. penn researchers and other scientists published their findings in 44 papers this week in the journal nature. the data is part of a larger research initiative with the translational research institute for space health (trish) and nasa. “our everyday functioning is comprised of all of these different functions of the brain that work simultaneously,” basner said. “so we try to learn, which of these are actually most affected by spaceflight and what could it mean?” central bucks students blast off into stem with nasa techrise challenge lenape middle school students built a rocket powered lander that nasa will test out. 9 months ago in 2021, scientists got a new opportunity to study this when four people made history and became the world’s first all civilian team to go into space and orbit earth multiple times before returning to the planet’s surface. the spacex inspiration4 mission included a billionaire entrepreneur and pilot, a cancer survivor and physician assistant, a data engineer and air force veteran, and a geoscientist and professor. during their three day trip, crew members recorded some of their physiological and mental health stats like heart rate, oxygen level, mood state, sleep quality, alertness and other metrics by running a series of neurocognitive tests and using apple watches and non invasive medical equipment. researchers took that data and studied different areas of health outcomes and changes. basner and his team at penn focused on how spaceflight affected cognition, behavior and psychological performance. “so we’re looking at things like attention, memory, learning, risk taking or emotional recognition,” basner said. “are you still able to interpret somebody who is emoting anger or fear or happiness? this is all very important and relevant for spaceflight spatial orientation.” the team found that some crew members experienced cognitive decline and issues in several categories during the early phase of flight, but the effects were temporary. all fully recovered later in the flight or shortly after returning to earth. “those transitional phases are really critical, where all of a sudden, oh, you’re in microgravity and your brain has to rethink how it’s interpreting those signals,” basner said. “there are a lot of changes that can affect your performance. this is what we saw.” christopher jones, an assistant professor of psychiatry at penn, said the effects varied greatly from person to person, which led to even more research questions. “is there an individual phenotype or something that we can help define and understand so we could potentially know how somebody with this makeup may respond to the spaceflight environment?” jones said. “are they going to be resilient or may they be vulnerable to some of the effects?” our virtual reality future, super earth space discovery, ballet brothers will we all be walking around with our phones strapped to our faces? we'll talk about vision pro. plus, nasa discovers a new planet   a super earth   that could support life. air date: february 6, 2024 12:00 pm the findings and data can be used to better inform safety protocols for everyday people who want to travel to space, basner said. it also can be used to set expectations for travelers who ultimately want to enjoy their time in space for the short time they are there. “the first few days in spaceflight can be pretty miserable, right?” he said. “we want to learn who is susceptible to that and also what we can do to mitigate those things in terms of medication or something you can do on the ground to prepare you for that period, because you want to enjoy it.” researchers from all over the country are working with the translational research institute for space health to build a database of information and health outcomes of civilian space travelers. the goal is to one day make it accessible to other scientists and experts around the world as space tourism continues to grow. get daily updates from whyy news! the free whyy news daily newsletter delivers the most important local stories to your inbox. whyy is your source for fact based, in depth journalism and information. as a nonprofit organization, we rely on financial support from readers like you. please give today. ‘uncharted territory’: philadelphians navigate growing old with hiv as more people survive longer about half of all people living with hiv today are over the age of 50. by 2030, older survivors could make up as much as 70% of that population. 2 weeks ago philly reports first suspected case of bird flu in an ill snow goose found near carroll park city health officials say the snow goose was found in west philadelphia on jan. 11. preliminary state testing was positive for bird flu. 2 weeks ago jefferson health and christianacare resident doctors join local wave of unionizing resident doctors from several major health care institutions in the region voted to form unions in the past two weeks. 3 weeks ago nicole leonard is a health and science reporter for whyy news. want a digest of whyy’s programs, events & stories? 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supported by un examen exhaustivo de los datos médicos recogidos en la misión privada inspiration4 en 2021 reveló descensos cognitivos temporales y cambios genéticos en la tripulación. by kenneth chang an extensive examination of medical data gathered from the private inspiration4 mission in 2021 revealed temporary cognitive declines and genetic changes in the crew. by kenneth chang the mission hinted at what space travel could look like in a more accessible future, while remaining in reach now to only the richest of the rich. by kenneth chang a crew of everypersons showed what space tourism could become in the future. by kenneth chang the inspiration4 mission successfully lifted off from florida, carrying with it an ambition of making spaceflight more accessible to the broader public. by kenneth chang la misión inspiration4 demuestra lo prometedor de los vuelos espaciales privados, pero también lo mucho que falta para que cualquiera pueda viajar a la órbita. by kenneth chang professional and amateur astronauts go through very similar training exercises. by kenneth chang by kenneth chang the inspiration4 launch is helping to raise money for the hospital, which helps treat pediatric cancer. by kenneth chang in addition to jared isaacman, the mission's commander, there are three other astronauts aboard the crew dragon capsule. by kenneth chang

thank you for visiting nature.com. you are using a browser version with limited support for css. to obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in internet explorer). in the meantime, to ensure continued support, we are displaying the site without styles and javascript. nature volume 632, pages 1145 1154 (2024)cite this article 29k accesses 18 citations 299 altmetric metrics details spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space1,2,3,4,5,6. yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on earth, underscoring the need for rapid development of space medicine databases, tools and protocols. here we present the space omics and medical atlas (soma), an integrated data and sample repository for clinical, cellular and multi omic research profiles from a diverse range of missions, including the nasa twins study7, jaxa cfe study8,9, spacex inspiration4 crew10,11,12, axiom and polaris. the soma resource represents a more than tenfold increase in publicly available human space omics data, with matched samples available from the cornell aerospace medicine biobank. the atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiome datasets, which reveal some consistent features across missions, including cytokine shifts, telomere elongation and gene expression changes, as well as mission specific molecular responses and links to orthologous, tissue specific mouse datasets. leveraging the datasets, tools and resources in soma can help to accelerate precision aerospace medicine, bringing needed health monitoring, risk mitigation and countermeasure data for upcoming lunar, mars and exploration class missions. with an exponential increase in launches since 2019, space is rapidly becoming more accessible1. multiple commercial and state sponsored groups are developing roadmaps to construct space stations, moon bases, mars colonies and other permanent establishments beyond earth1. although innovation across the aerospace sector makes these ambitions technologically achievable, the biomedical challenges for crews in these extraplanetary habitats still need to be addressed, as humans did not evolve to survive in such extreme environments. the clinical consequences of this evolutionary mismatch of spaceflight exposure and adaptation have revealed a plethora of challenges to long term space habitation, including a loss in bone density and muscle mass2, spaceflight associated neuro ocular syndrome3, perturbed immune function4 and spaceflight anaemia5. these physiological changes during spaceflight appear to imprint on the health status in humans; a chief example of this long term effect is the increased risk of cardiovascular pathology observed in astronauts compared with age matched controls6. before long term space habitation is feasible, these biomedical challenges must be understood and mitigated. however, the aetiologies driving them are not understood, with the low number of astronauts yielding limited opportunities for in depth biomolecular characterization. for example, two of the largest multi omic studies to date have been the nasa twins study, which has published an in depth molecular and cognitive profile of a single astronaut7, and the japanese aerospace exploration agency (jaxa) cell free epigenome (cfe) project, which has profiled cell free dna (cfdna) and cfrna in six astronauts8,9. thus, achieving statistical power requires integrating data from other cohorts, such as the marrow study, and other missions5,10. furthermore, these analyses are complicated by the substantial variation in physiological responses to spaceflight among astronauts. therefore, there is a need for increasingly large, detailed multi omic profiles of astronauts to characterize the diversity of physiological shifts as a function of spaceflight11. to achieve this end, we have leveraged the burgeoning commercial spaceflight industry. with the launch of spacex’s 2021 inspiration4 (i4) mission, a cohort of all civilian astronauts successfully completed a high elevation (585 km), 3 day orbital mission within a spacex dragon capsule. using recently developed protocols, the crew participated in a range of biospecimen collections before, during and after their mission12. we used the i4 biospecimens to deeply profile the effect of the stressors of spaceflight (for example, microgravity and space radiation) on crew physiology and health. we also compared these results with previous missions and control datasets, creating the largest to date molecular atlas of the effect of spaceflight on the human body, encompassing almost 3,000 samples and over 75 billion sequenced nucleic acids. collectively, these resources are referred to as soma, and the samples are linked to a cornell aerospace medicine biobank (cambank) that stores viably frozen specimens for future, additional analyses. as with earth based cohorts13, these accessible data   when profiled and aggregated at scale   will enable the development of both personalized and general medical guidance for astronauts14. a large group of subject matter experts in artificial intelligence has recently released recommendations focused on the importance of generating and archiving space data into the nasa open science data repository (osdr)15,16 to enable autonomous and intelligent precision space health systems, and to monitor, aggregate and assess biomedical statuses for future deep space missions17. in addition, the study of the parallels between the physiological effects of spaceflight and ageing, chronic disease and immune system disorders using omics data can pave the way for therapeutics applicable to conditions on earth. here we present a detailed guide to the soma resource, which includes the 2,911 samples collected during the i4 mission11,12, as well as spatial transcriptomics data, long read profiles of astronaut rna, microbiome data, exosome profiles and in depth immune diversity maps. additional spaceflight data were annotated and compiled into the soma portal to help contextualize gene, protein or metabolite dynamics, including data from the nasa twins study7, jaxa’s cfe mission8,9, single cell rna sequencing (scrna seq) data after simulated microgravity on peripheral blood mononuclear cells (pbmcs)18, and rat or mouse spaceflight data matched to human orthologues. in addition to rigorous dataset annotations, we detail (1) a comparison of conclusions on nasa twins study and flight dynamics comparing short duration and long duration missions, (2) cell type specific responses to spaceflight previously undocumented in astronauts, (3) cfrna expression profiles showing haematological responses during recovery from spaceflight, and (4) additional analyses on individual responses to spaceflight from proteomic, transcriptomic and microbiome data. data and samples generated in this study are available through soma (https://soma.weill.cornell.edu), nasa osdr (https://osdr.nasa.gov/bio/) and cambank (https://cambank.weill.cornell.edu/), which offer an unprecedented view of the multi system omics changes before, during and after spaceflight. to generate a comprehensive profile of the physiological changes of the i4 crew (29, 38, 42 and 51 years of age), 13 biospecimen sample types were collected and processed, including whole blood, serum, pbmcs, plasma, extracellular vesicles and particles (evps) derived from plasma, dried blood spots, oral swabs, nasal swabs, skin biopsies, skin swabs, capsule (spacex dragon) swabs, urine and stool specimens12. after collection, samples were subject to a battery of multi omic assays, including clinical (clia) whole genome sequencing, a clonal haematopoiesis panel, direct rna seq (drna seq), single nucleus rna seq (snrna seq), single nucleus assay for transposase accessible chromatin with sequencing (snatac seq), single cell b cell repertoire (bcr) and t cell repertoire (tcr) v(d)j sequencing, untargeted plasma proteomics (liquid chromatography tandem mass spectrometry), untargeted plasma metabolomics, cfdna sequencing, cfrna, metagenomics, metatranscriptomics and spatially resolved transcriptomics. in addition, chemokine, cytokine and cardiovascular biomarkers were quantified, and a clia lab (quest diagnostics) was used to perform a complete blood count and comprehensive metabolic panel (fig. 1a). datasets were generated across ten timepoints: three pre flight (l−92, l−44 and l−3), three in flight (flight day 1 (fd1), fd2 and fd3), one immediately post flight (r+1) and three recovery (r+45, r+82 and r+194) spanning 289 days (fig. 1b). assays were performed on all crew members unless otherwise noted (fig. 1b and supplementary table 1). a, omics and biochemical assays were performed on blood (whole blood, serum, pbmcs, plasma, plasma derived evps and dried blood spots), oral (microbiome swabs), nasal (microbiome swabs), skin (biopsy and microbiome swabs), environmental (env.; microbiome swabs) and excrement (excrem.; urine and stool) samples. b, the timepoints of this study are separated into four different categories: pre flight (l−92, l−44 and l−3), in flight (fd1, fd2 and fd3), post flight (r+1) and recovery (r+45, r+82 and r+194). the coloured circles indicate which assay was performed at each timepoint. assays were performed on all crew members, unless denoted with an asterisk. c, indicator for which assay types have been previously performed in spaceflight studies, broken down by the nasa twins study, jaxa studies and anonymized nasa cohort studies. anon., anonymized. a total of 2,911 samples were banked, with 1,194 samples processed for sequencing, imaging and biochemical analysis (supplementary table 1). these results and assays subsume and expand on work and protocols from previous missions, including the jaxa cfe study, the nasa twins study and some nasa astronauts (fig. 1c). this latter category spans studies primarily from the international space station (iss) that lack certain metadata, primarily duration spent in space and launch dates, to maintain astronaut anonymity. these studies include chemokine/cytokine biomarker panels (n = 46 astronauts), comprehensive metabolic panels, telomere length quantitative pcr (qpcr) and iss surface metagenomic profiling (fig. 1c). the soma resources were first compared with the nasa osdr database, which contains all publicly accessible human omics data from spaceflight and ground analogue studies. osdr hosts 76 human omics studies, of which 11 are from human primary cells exposed to spaceflight. the other studies encompassed cell line and ground studies, including high altitude studies (extended data fig. 1a and supplementary table 2), which were all merged with the soma dataset. once merged, the total number of sequenced nucleic acid molecules from this study represents a more than tenfold increase in the total amount of human omics data in the osdr (extended data fig. 1b), across all spaceflight studies, ground studies, cell line and primary cell experiments (extended data fig. 1 and supplementary tables 2 and 3). the data from the missions were then divided into three analysis timeframes: (1) flight profiles, (2) recovery profiles and (3) longitudinal profiles (extended data fig. 1c). flight profiles reveal the most immediate effect of spaceflight, recovery profiles catalogue changes that occur after return to earth, and the longitudinal profiles identify changes that have not returned to baseline after returning to earth. we focused on several outputs for the resource, including first calculating differentially expressed genes (degs) for (1) pbmc snrna seq, (2) whole blood drna seq, (3) skin spatially resolved transcriptomics, and (4) cfrna. we also mapped differentially methylated genes from whole blood drna seq, differentially accessible regions from pbmc snatac seq, isotype identification from tcr and bcr v(d)j sequencing, differentially abundant proteins from plasma and evp proteomics, differential metabolites from liquid chromatography mass spectrometry metabolomics, and microbial differentials from metagenomic and metatranscriptomic assays (extended data fig. 2), with all raw and processed data annotated in the osdr (supplementary table 4). telomere elongation has been previously described in three astronauts who stayed for 6 months to 1 year aboard the iss7,19,20, but it was unclear how quickly such a phenotype appeared in astronauts. the average telomere length in all i4 crew members increased during spaceflight (17 22% longer), and this trend was statistically significant (mixed effects linear model p = 0.0048; fig. 2a). this finding is particularly notable, given the shorter mission duration (3 days total) and higher elevation of the i4 mission than the iss studies, indicating that telomere length dynamics respond much more rapidly to spaceflight than previously observed. a, normalized average telomere lengths for i4 crew members, pre flight, during flight and post flight, determined by qpcr analyses of blood (dna) collected on dried blood spot (dbs) cards (n = 32 samples for 4 independent participants across 8 timepoints). two sided p values were derived using a mixed effects linear model that incorporated fixed effects for different timepoints (pre flight, in flight, post flight and recovery) and random effects to account for variations among participants. the centre of the boxplots represents the median, the box hinges encompass the first and third quartiles, and the whiskers extend to the smallest and largest values no further than 1.5 × the interquartile range (iqr) away from the hinges. b, changes in downregulated (dn; purple) and upregulated (up; orange) gene expression log2 fold change directionality post flight from the twins study versus i4 in cd19 b cells, cd4+ t cells and cd8+ t cells (statistical significance was determined by a two sided wilcoxon rank sum test). the number of genes is shown below the violin plots. the centre white dot represents the median, and the white line shows the range of the first and third quartiles. c, relative cytokine/chemokine abundance pre flight, post flight and during recovery in the i4 crew versus the nasa twins study and anonymized nasa astronaut cohorts for ccl2, il 10 and il 6. mlbt, multiplexing laser bead technology. pre, pre flight median; post, post flight (r+1). d, relative abundance of bdnf and il 19 pre flight, post flight and during recovery in the i4 crew. in panels c and d, the two sided p values and adjusted q values were derived using a mixed effects model that incorporated fixed effects for different timepoints (pre flight, in flight, post flight and recovery) and random effects to account for variations among participants, except in the twins study, which had a single participant (n = 1). p values with an asterisk have a q > 0.05 after multiple correction testing. we then compared the degs and cytokine changes from the twins study with those observed in the snrna seq data from the i4 mission, as well as compared with the expected degs of the assay from replicate negative control donor pbmcs (see methods). the cross mission deg comparison highlighted a consistent response between both types of t cells, including cd4+ and cd8+ markers (552 and 608 degs, respectively, both <2.2 × 10−16), across both sorted t cells or single cell annotated cells (fig. 2b). conversely, b cells were less responsive to spaceflight, as expected from previous work in the twins study7, which showed b cells as either not significant or less responsive to spaceflight. for the four overlapping cytokines measured in the twins study with our panel, we found significant increases in three: il 6 (p = 0.014), il 10 (p = 0.021) and ccl2 (p = 0.040) (fig. 2c); these cytokines also showed changes and similar increases in other long duration (more than 6 months) crews (fig. 2c). however, we also ran a differential analysis of all cytokines detected on the i4 mission, to detect any differences from the twins study. indeed, the levels of bdnf showed a statistically significant decrease (p = 0.00011, q = 0.0153), and il 19 levels showed a statistically significant increase (p = 0.00015, q = 0.0153) during the post flight (r+1) timepoint that returned to baseline during recovery (r+45 and r+82; fig. 2d). beyond recapitulating known biomarkers of spaceflight, the atlas integrated newer assays that were not available in previous missions, with a particular emphasis on rna profiling. the first novel assay was spatially resolved transcriptomics on skin biopsies, which were obtained from all crew members during one pre flight timepoint (l−44) and the day after landing back on earth (r+1). the 4 mm biopsies were stained with markers for dna, panck, fap and α sma and then processed with the nanostring/bruker geomx digital spatial profiler, where regions of interest were selected based on the tissue structures identified by the fluorescence staining (extended data fig. 3a). after filtering out outliers, the rna counts were used for downstream data analysis, generating 95 regions of interest across four skin compartments: outer epidermis, inner epidermis, outer dermis and vasculature (extended data fig. 3b,c). this analysis revealed a distinct set of degs, including jak stat signalling, and melanocyte signatures (fig. 3). a, cell type deconvolution using bayes prism with tabula sapiens as a reference. top ten cell types by average fraction across all samples with all remaining cell types summed together as ‘other’. b, cell type of origin for hepatocytes, endothelial cells, haematopoietic stem cells and melanocytes, which all show increased abundance during post flight and recovery timepoints. c, cell proportion changes in different layers of the skin from spatially resolved transcriptomics on skin biopsies. predicted melanocyte abundance changes are significant in the inner epidermal and outer dermal skin compartments. in panels b and c, n = 4 independent participants across 7 timepoints. the centre of the boxplots represent the median, the box hinges encompass the first and third quartiles, and the whiskers extend to the smallest and largest values no further than 1.5 × iqr away from the hinges. ns, not significant; **p ≤ 0.01; ***p ≤ 0.001. a second rna assay for spaceflight integrated into soma was cfrna profiling, which has recently been established as a dynamic tool for mapping temporal alterations in cfrna composition and cell lysis21. however, bulk cfrna had not been utilized to measure the response of spaceflight until the jaxa cfe study8,9 and the i4 mission12. using principal component analysis, we identified a distinct separation in cfrna profiles pre flight versus post flight and recovery for i4, suggesting a systemic physiological shift probably induced by space travel (extended data fig. 3d). this was further reflected in the differential abundance of cfrna genes across various timepoints, revealing specific patterns of noncoding expression (extended data fig. 3e) and rna types (extended data fig. 3f) that correspond with the spaceflight timeline. the cell type proportions inferred from the cfrna profiles also exhibited spaceflight associated variation over time and showed variation distinct from a set of healthy blood donor controls (n = 35; fig. 3a and supplementary table 5). cell types that showed significant post flight shifts in proportion included hepatocytes, kidney endothelial cells, haematopoietic stem cells and melanocytes (fig. 3b and supplementary table 5). of note, the melanocyte cell proportions that demonstrated significant changes post flight (fig. 3c) were also found in the spatial skin transcriptomics data, providing additional evidence of adaptive skin responses to the space environment. a third novel rna method applied to these spaceflight samples focused on rna isoforms and rna modifications (epitranscriptome), through drna seq on the oxford nanopore technologies promethion and deep rna seq (more than 400 million reads per sample) on the ultima genomics ug100. these data quantified genes that were differentially expressed and displayed differential n6 methyladenosine methylation (extended data fig. 4a,b), or both, and were analysed for enriched gene ontology pathways. we identified a set of sites (set m i; extended data fig. 4b) that undergoes hypomethylation during recovery, another set (set m ii) that is detectably hypermethylated from spaceflight, and a set (set m iii) that exhibits novel hypermethylation during recovery and longitudinally as well. the common pathways in all three sets (extended data fig. 4b) showed evidence of radiation and telomere response, including ‘tsai response to radiation therapy’ and ‘wiemann telomere shortening’22. in addition, the set of downregulated pathways after landing (recovery) was distinct, including genes associated with breathing regulation (for example, co2 and o2 take up and release by erythrocytes), which matches those pathways associated with crew response ranges (below, fig. 5). although further studies are needed to validate and delineate the potential mechanisms of these rna dynamics (cfrna, spatial and rna modifications), these pathways suggest a potential relationship between rna expression and methylation in regulating haematological and dermatological functions upon return to earth. leveraging the time series data, we next analysed pbmc gene expression from snrna seq to discern whether unique degs are present at each timepoint. we examined degs from immediately post flight (fp1) through the recovery profiles (rp1 and rp2) to observe how gene expression profiles are re established after spaceflight. the number of degs was used to quantify the severity and recovery of crew response, and we also compared identified degs from a negative control group, including two healthy donors and read depth  and cell count matched permutation group (extended data fig. 5), with an average of more than 700 cells per crew member, per timepoint, per cell type. the deg count (adjusted p < 0.05, |log2 fold change (fc)| > 0.5) decreased from fp1 to rp1 in cd16+ monocytes, dendritic cells, natural killer cells, ‘other’ t cells (but not cd4+ or cd8+), uncategorized (‘other’) cells and in pseudobulk (calculated from additive counts across cell types to represent pbmcs). however, the deg count increased in b cells, cd4+ t cells, cd8+ t cells and cd14+ monocytes (fig. 4a); by rp2, all cell types had lower deg counts than at fp1 and began to approach the expected noise range of single cell degs (fig. 4a). a, number of degs from pbmc snrna seq for each cell type during the flight, recovery and longitudinal profiles (adjusted two sided p < 0.05, |log2fc| > 0.5). nk, natural killer. b, fraction of degs shared with fp1 at rp1, rp2 and lp2 for each cell type. c, directionality of log2fc between fp1 and rp1 and rp2 for degs present in both profiles. d, bar chart of pathways of degs present in rp1 that were absent in fp1 in monocytes and t cells. bars are shaded by the false discovery rate (fdr) value, and the enrichment ratio is on the x axis. as deg counts were higher at rp1 than at fp1 for several cell types, we hypothesized the introduction of distinct degs after landing back on earth. first, we calculated the percentage of degs unique to fp1 at both rp1 and rp2, focusing on cell type specific degs (fig. 4b). by lp2 (l−92, l−44 and l−3 versus r+82), we observed that nearly all differential gene expression was driven by the same set of genes that were differentially expressed at fp1, with the exception of cd14+ monocytes, which had a unique longitudinal profile not strongly connected with the deg responses in other cells. with the exception of cd14+ monocytes, the rp1 profile is distinct in the abundance of degs not present in fp1, but this perturbation almost entirely (more than 95% of genes) disappeared after flight (rp2 and lp2). from the degs shared with fp1, we observed that gene expression directionality reversed for nearly all degs between fp1 and each recovery profile (fig. 4c), indicating a return to baseline for those degs. the exception to this were two genes from the cd14+ monocyte population   ahr (log2fc of 0.742 (fp1) and log2fc of 0.808 (rp1)) and peli1 (log2fc of 0.539 (fp1) and log2fc of 0.560 (rp1); fig. 4c)   in which there was a positive log2fc expression at both fp1 and rp1. from the degs that were unique to fp1, we next quantified the uniformity of the pathway enrichment between two pbmc lineages: t cells (cd4+ and cd8+) and monocytes (cd14+ and cd16+; supplementary table 6). of note, 211 (70.8%) genes were unique to individual cell types and 87 (29.2%) were shared between two or more cell types (extended data fig. 6a). to identify enriched pathways among the gene set for each cell type, overrepresentation analysis was performed on kyoto encyclopedia of genes and genomes (kegg) pathways (supplementary table 6). even though 70.8% of genes were unique to each cell type, their response was more convergent; unique pathways only ranged from 4.2% (cd4+ t cells) to 42.5% (cd14+ monocytes; extended data fig. 6b). yet some pathways were cell type specific, such as the circadian entrainment pathway in cd14+ monocytes, with genes gng2, gnas, prkcb, creb1 and camk2d driving the overrepresentation from the gene set for this pathway (fig. 4d). in addition, our data suggest that overrepresented pathways are sometimes more associated with cell lineage (for example, all t cells) than with the individual cell type (for example, cd4). this is evident from the longevity regulating pathway that shares the prkacb, nfkb1 and pik3ca genes between both cd4+ and cd8+ t cell populations (fig. 4d). in addition, we found that certain pathways can be enriched across specific cell types belonging to different lineages. the inflammatory mediator regulation of the ‘trp channel’ pathway, for example, was overrepresented in both cd8+ t cells and cd14+ monocytes, with each cell type contributing different gene sets associated with the pathway (fig. 4d). other pathways, such as the il 17 signalling pathway, contain mixtures of shared genes and unique genes and are significantly overrepresented across all cell types (fig. 4d). this also indicates that although cell types are distinct, they appear to have a set of core pathways in response to spaceflight, with 30 60% of overrepresented pathways shared both within and between lineages (extended data fig. 6b). to examine the chromatin accessibility and regulatory landscape in each cell population, we then analysed the transcription factor binding site (tfbs) motif accessibility changes from snatac seq data to identify the top motifs in flight and recovery profiles (extended data fig. 7). we first observed that increased gene expression was correlated with more accessibility at the transcription start sites, and closed chromatin was associated with downregulated genes (all p < 0.05, wilcoxon rank sum test, for all cell types; extended data fig. 7a). the motif accessibility changes associated with recovery profiles recapitulated the trend in gene expression and chromatin accessibility data, which showed lower accessibility in regions of the genome with closed chromatin and higher expression in regions of more accessibility (extended data fig. 7b). in addition, we showed the top five upregulated and downregulated tfbs motifs per cell type in fp1, rp1 and rp2, which revealed both common and distinct motifs and their accessibility across cell types (extended data fig. 7c e). these data also provided further evidence of cell type specificity in the differences of chromatin and transcription factor accessibility dynamics. to understand individual variation during spaceflight, the coefficient of variation was measured across microbial, proteomic, cytokine and gene expression normalized count data, calculated by time interval (pre flight, in flight, post flight and recovery). normalized coefficient of variation scores (see methods) were calculated for each body area from the microbial swabs from both metagenomic and metatranscriptomic data. the oral and forearm microbial variation (extended data fig. 8a,b) showed rothia mucilaginosa and staphylococcus epidermidis as leading variable strains, but each body site has distinct higher coefficient of variation species (other body sites are shown in extended data fig. 8c j and supplementary table 7). similarly, abundance standardized coefficient of variation scores were calculated for evp proteomic, plasma proteomic, metabolomic, rna seq, drna seq, and cytokine abundance normalized protein and gene counts (extended data fig. 9a f). to characterize the participant to participant variation and null distributions, we also calculated the differentials for fp1 along with label permutation testing on these calculations to confirm that post flight coefficient of variation was not higher than other timepoints (see methods; supplementary table 8). we then utilized the data across missions (i4, twins study and jaxa), assays (scrna seq, cfrna, bulk rna seq and proteomics) and cell types (cd4, cd8, cd14 and cd16) to find the most recurrent pathways associated with spaceflight. the most enriched pathways were antigen binding, haemoglobin, cytokine signalling and immune activation, which confirmed the deg related signatures and also validated the signatures from our i4 mission (fig. 5). moreover, the nasa twins study data and cfrna profiles from the jaxa study confirmed many of the top ranked pathways, while also showing differences between bulk blood rna and protein markers and purified cell populations. these data indicate that leveraging both bulk and sorted cell populations can help to clarify signals coming from crew blood dynamics related to spaceflight. enriched pathways in post flight compared with pre flight across various assays and missions, analysed using fast gene set enrichment analysis (fgsea). the colour represents the normalized enrichment score, whereas the dot size indicates benjamini hochberg adjusted q values. only the pathways with unadjusted p < 0.01 are shown. the barplot shows the total number of comparisons with q < 0.05 for every pathway, coloured by the direction of the enrichment. the column ‘mixed cell type’ refers to whole blood for i4 data and lymphocyte depleted cells for the nasa twins study. gobp, gene ontology and biological process; gomf, gene ontology molecular function; hp, human phenotype; lps, lipopolysaccharides; npc, neural progenitor cells; pid, pathway interaction database; wp, wikipathways. this study introduces full accessibility of astronaut data to the scientific community. datasets are accessible through an online web portal and scientific data repositories, as well as controlled access to more sensitive data (for example, genetic sequence data) and physical specimens. the online web portal splits the data into three data browsers: the soma browser, the i4 single cell browser and the microbiome browser (extended data fig. 10a c). the soma browser (https://soma.weill.cornell.edu/apps/soma_browser/) enables visualization of gene expression (bulk rna seq, snrna seq, cfrna seq and spatially resolved transcriptomics), mass spectrometry (plasma proteomics, plasma metabolomics and plasma evp proteomics) and microbial (metagenomic and metatranscriptomic) data. gene expression and protein abundance are visualized for each astronaut by timepoint, with fold change values, statistical significance (q value) and summary tables. any selected gene is also then plotted across data for other missions, including the jaxa cfe study, the nasa twins study, mouse spaceflight datasets from nasa osdr and genelab, and control cohorts. for additional granularity, the single cell browser (https://soma.weill.cornell.edu/apps/i4_multiome/) provides visualizations specific to single cell gene expression (scrna seq) and chromatin accessibility (scatac seq) data, and includes quality metrics, cell type annotations, gene co expression and chromatin accessibility magnitude estimates. finally, the microbiome browser contains metagenomic and metatranscriptomic boxplots (https://soma.weill.cornell.edu/apps/i4_microbiome/) from each timepoint of the study, spanning eight skin locations, deltoid swabs collected pre skin biopsy, swabs of the spacex dragon capsule and stool samples. the remaining biospecimens from this study have been preserved and catalogued for continued use by the scientific community (https://cambank.weill.cornell.edu/). these samples include venous blood plasma, venous blood serum, viably frozen pbmcs, vacutainer red blood cell pellets, urine (both crude and with nucleic acid preservative), extracted saliva nucleic acids (dna and rna), extracted whole blood total rna, extracted skin swab nucleic acids (dna and rna) and extracted stool nucleic acids (dna and rna). a subset of these samples will be available for additional assays and hypothesis testing by other groups, and the remainder are allocated for long term biobanking. these data and specimen resources for astronauts can help enable larger cohorts for increased statistical power and also for new biomedical technologies that will emerge in the future. overall, these data represent a comprehensive clinical and multi omic resource from commercial and non commercial astronaut cohorts, creating, to our knowledge, the first ever aerospace medicine biobank, while providing a platform for private citizens to contribute to future astronaut biomedical studies. in addition, we have demonstrated that short duration, high elevation (585 km) spaceflight results in broad ranging molecular changes, in which some of these changes mirror what has been observed during longer duration spaceflight, including elevated cytokines, telomere elongation and gene expression changes for immune activation, dna damage response and oxidative stress. although more than 95% of markers return to baseline in the months after the mission had ended, some proteins, genes and cytokines appear to be activated only in the recovery period after spaceflight and persist post flight for at least 3 months. these results collectively indicate a dynamic recovery profile that substantially reverses the direction of differential gene expression in multiple key biological pathways from the post flight timepoint (r+1) and afterward. this suggests that re adaptation to earth activates a range of restorative mechanisms that help to recover, at least in part, the physiological stress imposed by exposure to the space environment. the systematic analysis of the molecular and cellular changes observed post flight afford us with a unique opportunity to capture naturally occurring health restoring mechanisms, which can be used for therapeutic target discovery. furthermore, we observed a nuanced regulatory landscape, in which enriched recovery pathways are both unique to individual cell types and span cell types in unique combinations. we have carefully indexed various profiles for flight, recovery and longitudinal analysis that are annotated in processed data files available in the nasa osdr. the rp1 profile indicates that we need more frequent sampling in the 1 2 months directly after flight to untangle the gene and pathway responses during re adaptation from spaceflight. this will be especially true during longer missions, in which re adaptation will probably be more intense. of note, these data are, to our knowledge, the first ever joint single nucleus chromatin profiles (rna and atac) for astronauts, and they also leverage new methods that can track gene expression and epigenetic changes within the same cells. this single cell, dual measurement assay provides new data on the molecular changes and regulatory response to spaceflight (for example, chromatin and tfbs accessibility), and the data revealed distinct levels of stress and adaptation by each cell type. specifically, the t cell and monocyte cell populations (cd14 and cd16) had the largest changes in expression and response of any cell type. the differences between pbmc subpopulations also suggest that single cell sequencing can be helpful for delineating unique cell type responses in future studies as well. indeed, although the immune system and haematopoietic systems both show thousands of transient changes at the gene expression level, the chromatin architecture is distinctly disrupted, in both scale and duration, in these cd14+ and cd16+ monocyte populations. these cell types were also found to be disrupted in the nasa twins study7,23, and thus represent a key cell type to be studied for future missions. the cfrna, drna and spatial rna profiles revealed unique profiles that differed based on recovery and longitudinal analysis, suggesting that the multi omic footprint of spaceflight is much wider than previously observed. although some focused studies of cfrna have shown that it can be used to detect mitochondrial increase in blood related to spaceflight7,8,9,24, to our knowledge, it had never been applied as a ‘full body molecular scan’ to detect differential tissue and cell stress. of note, the soma resource enables comparisons of the cfrnas and cell encapsulated rnas, as well as the exosomal fractions, all within the same framework, which is essential for delineating and ranking the cells and tissues in the body that are the most disrupted by spaceflight. similar to the utility of single cell data23, the granularity of seeing cell lysis from all tissues across the body in one assay makes cfrna profiling an ideal addition to some of the proposed standard measures for spaceflight monitoring. so far, cfrna data indicate that each part of the body may show its own transcriptional response, shedding rate or rna excretion rates, and thus each tissue should be examined on its own and then compared with other sites and assays. similarly, in the microbiome data, the taxonomic classifications yielded differences in variation by body site, timepoint and crew member (extended data fig. 8), indicating the need for multi site and multi omic sampling for ideal understanding of microbiome changes associated with spaceflight. however, this study is not without limitations. although cell specific comparisons could be made between the i4 mission and previous studies, the assays and collection protocols were slightly different (for example, column purification versus droplet sorted cells), and thus comparisons will be imperfect. in addition, although the same tube types and methods were used whenever possible, cross mission comparisons will inevitably include noise from various other types of technical variation, including batches of library preparation and extraction kits, slightly different collection intervals (l−3 versus l−10) and different sequencing or profiling technologies (for example, illumina versus ultima or liquid chromatography tandem mass spectrometry versus nulisaseq). finally, as our comparisons to other nasa and jaxa datasets span, at most, 64 astronauts, these data are not sufficient to guide medical interventions or inference of mechanisms. as such, these soma data and resources should be viewed as preliminary molecular maps of the response of the human body to spaceflight. nonetheless, the data from the i4 mission will be an invaluable resource for future studies. deep analyses of secretome profiling25, single nucleus multiome26, viral activation and ecological restructuring27, skin spatial transcriptomic profiling28, epitranscriptomic profiling22, and genome integrity and clonal haematopoiesis29 have already leveraged this resource. in future missions, additional biomedical profiling can help to delineate the short term and long term health effects of spaceflight, including changes in telomere length dynamics, dna methylation, non coding rnas, as well as additional sample types, such as hair follicles, tears, sperm and other biospecimens. indeed, the remaining samples from the i4 mission have been biobanked for just this reason and to help the scientific community tackle future objectives12. in addition, aliquots of dna, rna, protein, serum, urine and stool from the protocols performed in this paper have acquired consent for release and are available (https://cambank.weill.cornell.edu/) for request, in which researchers can then append new results to this extensible soma repository. differences between the biomedical and cellular responses of crew members may be caused by several factors, including inter individual genetic differences (fig. 5), the duration of the mission, the higher flight elevation (585 km), the unique environment of the spacex dragon capsule, or a combination of these and other factors. to address these hypotheses, other molecular assays can be informative for future missions, including other epigenetics and chromatin conformation assays. for example, we have investigated using the method cleavage under targets and release using nuclease (cut&run) to profile histone modifications using 5,000 and 10,000 t cells as assay input (supplementary fig. 3a), down from the 10 million cells recommended in the original protocol30. t cells were collected from c002 during the r+194 recovery timepoint, but showed high variance at lower input. nonetheless, the combination of current modifications profiled can be used to annotate active enhancer regions in the genome (supplementary fig. 3b), which is a novel profile for astronauts, and opens the door to better understanding of the gene regulatory changes induced by spaceflight for each crew member. molecular changes described here can also help to guide research and countermeasure development, but are only the start of the process of mitigating risks, especially as year long and multi year space habitat missions will represent greater biomedical challenges. to aid in this effort, the soma resource will continue to expand as further samples are sequenced from the i4 mission11,12 and samples are collected from future missions that travel farther into space, and then compared with other longitudinal, multi omics cohorts31. biospecimen samples have been collected and processed from polaris and axiom crews, and this atlas also represents an open call for research participation for astronauts from any commercial or governmental programs. finally, although the multi omic data and resources from the i4 crew represent the largest release of data from astronauts to date, the i4 crew is still a small cohort, and represents only the first step towards resolving the many hazards and needs for long term missions32, building towards enough statistical power and contextualization of normal human biological variation33,34. fortunately, one of the crew members for i4 will continue to donate to the soma biobank for multiple missions, including the polaris dawn mission, and data and samples from additional crews (for example, long term twins study follow up, axiom saudi, jaxa and malta missions) are now being collected and integrated. these cross mission datasets create a unique opportunity for long term, in depth analysis of the effect of spaceflight on the human body. such data are especially important as missions travel farther away from earth35 and for longer periods of time, in which the data and biomedical discoveries can help to prepare commercial and state sponsored agencies for the lunar, mars and exploration class missions. all participants consented at an informed consent briefing at spacex, and samples were collected and processed under the approval of the institutional review board at weill cornell medicine, under protocol 21 05023569. all crew members consented to data and sample sharing. full methodology for sample preparation, nucleic acid/protein extraction, sequencing, mass spectrometry and analysis are reported in supplementary note 1. sample collection has been previously reported12. differential abundance analyses of cytokines and other analytes were conducted using a mixed effects model. this model included fixed effects for time, treated as a categorical variable with levels corresponding to preflight (l−92, l−44 and l−3), immediate return (r+1) and recovery periods (r+45, r+82 and r+194). in addition, participant specific effects were incorporated as random effects in the model. the p values for the coefficients obtained from this model were adjusted for multiple comparisons using the benjamini hochberg procedure. we acquired cryovials of pbmcs from a healthy man 22 years of age (allcells) and stored them in vapour phase liquid nitrogen cryotanks. two cryovials from this donor were thawed and processed on two different days in the same week, at the same laboratory, using the 10x genomics demonstrated protocol called nuclei isolation for single cell multiome atac + gene expression sequencing (cg000365). from each day’s nuclei suspension, atac and gene expression libraries were generated (in technical triplicates on the same chip) according to the chromium next gem single cell multiome atac + gene expression user guide (cg000338) and sequenced on a novaseq 6000 sequencer. the resulting single nucleus gex and single nucleus atac files were aligned using the cellranger arc pipeline (v2.0.2) from 10x genomics against the human reference genome hg38. quality control and cell annotation were performed on the sngex gene cell matrices using the r seurat package (v4.2.0)36. subpopulations were clustered and labelled using a publicly available azimuth human pbmc reference37 in conjunction with seurat’s supervised clustering functionality. deg analysis for labelled subpopulations was performed using the findmarkers functionality of seurat, with a log fold change (logfc) cut off point of 0.5. p values of resultant genes were measured using the wilcoxon rank sum test and deemed significant for p < 0.05. correlation of chromatin accessibility and gene expression changes in fp1 was characterized by summing up the accessibility in a promoter window consisting of the transcription start site ± 500 bp for every cell in a given cell type across every gene, normalizing it to counts per million, taking the log2 difference between the different timepoints and matching it to the log2fc from the differential rna analysis. degs from each cell type from the pbmc 10x genomics single cell data were filtered for |logfc| > 0.5 and adjusted p < 0.05 for the fp1, rp1, rp2 and lp2 profiles. an upset plot of shared genes was generated using intervene38. overrepresented pathways were calculated using webgestalt39 using the default parameters and the kegg database. pathways included in the analysis were within the top 40 lowest false discovery rate values or all pathways with a false discovery rate under 0.05. chromvar40 was used for the analysis of sparse chromatin accessibility from 10x genomics single cell data. the findmarkers function of the seurat package was used for differential analysis with setting mean.fxn as rowmeans and fc.name = “avg_diff”. the top five differentially accessible transcription factor motifs from each cell type from the pbmc 10x genomics single cell data for the fp1, rp1 and rp2 were selected for visualization by heatmaps. heatmaps were generated by the complexheatmap r package. to distinguish the analytes that varied with the greatest magnitude between individual crew members (c001, c002, c003 and c004), a coefficient of variation (cv) calculation was applied across measurements collected for each: metagenomic species, metatranscriptomic species, plasma protein abundance, evp protein abundance, metabolite abundance, cytokine abundances (alamar bio) and gene expression values (oxford nanopore drna seq and ultima rna seq). cv calculations were performed using the formula ‘np.std(x, ddof = 0)/np.mean(x)’, where ‘x’ is the array of normalized analyte values and ‘np’ refers to the numpy scientific computing package (v = 1.26). cv calculations were split into pre flight (l−92, l−44 and l−3), post flight (r+1) and recovery (r+45 and r+82) intervals. the metagenomic and metatranscriptomic data also include the in flight (fd2 and fd3) interval. before performing the cv calculation, data were first normalized. the ‘limma’ r package was applied to the plasma proteomic, evp proteomic and metabolite data (v3.52). deseq2 (v1.36.0) was applied to the oxford nanopore drna seq and ultima rna seq data. for microbiome data, to measure individual contributions per astronaut and for each tissue type (‘armpit’, ‘forearm’, ‘nasal’, ‘oral’, ‘post auricular’, ‘t zone’, among others), we averaged metaphlan4, species level, relative abundance values across our collected sample points. cvs were calculated for individual genes, proteins and microbial organisms. an abundance standardized cv calculation was also performed to correct for the mean/cv relationship in the assays. first, the normalized abundance values across all the analytes of a given dataset were split into approximately 100 mean abundance quantiles (m_q where q is 1 100 or fewer, in case it resulted in less than 10 points per quantile group). for each quantile group, the mean and the standard deviation of cv values for the analytes belonging to m_q were calculated (cvmean_q and cvs.d._q, respectively) to prepare the mean/cv distribution reference set across all timepoints and samples. then, for a given timepoint, the cv calculated for each analyte was matched to the corresponding cvmean_q and cvs.d._q based on cross referencing to the m_q interval overlap. finally, the abundance standardized cv was calculated as the z score of the cv as (cv − cvmean_q)/(cvs.d._q). permutation testing of the post flight versus pre flight difference was performed by repeating this procedure 10,000 times on shuffled labels for samples, taking the difference. rank and z score of the observed value were calculated against the random permutations to order the genes and used as input to fgsea for pathway enrichment analysis. gene ontology analysis on abundance standardized cvs was performed with enrichr41,42 using the default settings. in depth methods and protocol information for all assays in fig. 1a is located in supplementary note 1. further information on research design is available in the nature portfolio reporting summary linked to this article. datasets have been uploaded to two data repositories: the nasa osdr (https://osdr.nasa.gov; comprising nasa genelab15 and the nasa ames life sciences data archive16,32). 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multiple biospecimen collection locations and nasa (80nssc21k0316). the nasa osdr thanks the nasa space biology program and the nasa human research program. s.a.n. thanks nasa (80nssc19k0426 and 80nssc19k1322). we thank the scientific computing unit at weill cornell medicine, including r. ahmed, a. mahmoud and j. hargitai; j. j. hastings for collections; i4 logistics and k. j. venkateswaran for microbiome guidance; and the nasa genelab and nasa alsda teams for customizing solutions for data accessibility in the osdr. j. kim thanks the mogam science foundation and was supported by the basic science research program through the national research foundation of korea (nrf) funded by the ministry of education (rs 2023 00241586). the astronaut cytokine data were provided from the nutritional status assessment project and the biochemical profile projects, which were funded by the human health countermeasures element of the nasa human research program. n.h. thanks z. wan and j. gu for providing the lists of tissue specific and tissue enriched proteins compiled from the human protein atlas and help with the gsea analysis. r.g. receives funding from pfizer, biohaven pharmaceuticals, leo pharma a/s and the howard and abby milstein foundation. l.p. thanks the association of transdisciplinary society of personalized oncology for combating cancer for financial support through the postdoctoral research fellowship stop cancer. d.c.l. acknowledges support from the children’s cancer and blood foundation, the malcolm hewitt weiner foundation, the manning foundation, the sohn foundation, the theodore a. rapp foundation and the ahepa vth district cancer research foundation. s.m.b. thanks nasa (80nssc19k0434). a.m.m. is funded by nci r35 ca220499. we thank f. wu and d. winer for data analysis and interpretation of data. department of physiology and biophysics, weill cornell medicine, new york, ny, usa eliah g. overbey, jangkeun kim, braden t. tierney, jiwoon park, nadia houerbi, alexander g. lucaci, sebastian garcia medina, namita damle, kirill grigorev, evan e. afshin, krista a. ryon, christopher r. chin, jonathan foox, craig westover, jeremy wain hirschberg, jacqueline proszynski, marissa burke, ashley s. kleinman, daniel j. butler, christopher mozsary, jan krumsiek, cem meydan & christopher e. mason the hrh prince alwaleed bin talal bin abdulaziz alsaud institute for computational biomedicine, weill cornell medicine, new york, ny, usa eliah g. overbey, jangkeun kim, braden t. tierney, jiwoon park, nadia houerbi, alexander g. lucaci, sebastian garcia medina, kirill grigorev, evan e. afshin, karolina sienkiewicz, annalise schweickart, jonathan foox, jan krumsiek, cem meydan & christopher e. mason bioastra inc., new york, ny, usa eliah g. overbey & christopher e. mason center for stem, university of austin, austin, tx, usa eliah g. overbey albert einstein college of medicine, bronx, ny, usa deena najjar tri institutional biology and medicine program, weill cornell medicine, new york, ny, usa karolina sienkiewicz, matthew mackay, annalise schweickart, maria a. sierra, gabriel deards, chandrima bhattacharya & jan krumsiek children’s cancer and blood foundation laboratories, departments of pediatrics and cell and developmental biology, drukier institute for children’s health, weill cornell medicine, new york, ny, usa laura patras, serena lucotti, irina matei & david c. lyden department of molecular biology and biotechnology, center of systems biology, biodiversity and bioresources, faculty of biology and geology, babes bolyai university, cluj napoca, romania laura patras department of stem cell biology and regenerative medicine, keck school of medicine, university of southern california, los angeles, ca, usa remi klotz, veronica ortiz & min yu buck institute for research on aging, novato, ca, usa matias f. valenzuela & david furman department of medicine, division of endocrinology, weill cornell medicine, new york, ny, usa ezequiel dantas meyer cancer center, weill cornell medicine, new york, ny, usa ezequiel dantas, irina matei, david c. lyden & ari m. melnick department of microbiology & immunology, vagelos college of physicians & surgeons, columbia university irving medical center, new york, ny, usa theodore m. nelson space biosciences division, nasa ames research center, moffett field, ca, usa egle cekanaviciute, lauren m. sanders & sylvain v. costes department of health, nutrition, and food sciences, florida state university, tallahassee, fl, usa s. anand narayanan sovaris aerospace, boulder, co, usa caleb m. schmidt, michael a. schmidt & julian c. schmidt advanced pattern analysis and human performance group, boulder, co, usa caleb m. schmidt, michael a. schmidt & julian c. schmidt department of systems engineering, colorado state university, fort collins, co, usa caleb m. schmidt space exploration technologies corporation (spacex), hawthorne, ca, usa sean mullane, seth stravers tigchelaar, steven levitte & jaime mateus division of pediatric gastroenterology, stanford university, palo alto, ca, usa steven levitte department of neurosurgery, houston methodist research institute, houston, united states marissa burke nancy e. and peter c. meinig school of biomedical engineering, cornell university, ithaca, ny, usa conor loy, omary mzava, joan lenz & iwijn de vlaminck department of medicine, division of hematology/oncology, weill cornell medicine, new york, ny, usa doru paul, ari m. melnick & cem meydan department of environmental and radiological health sciences, colorado state university, fort collins, co, usa lynn e. taylor & susan m. bailey trialx inc., new york, ny, usa chintan o. patel, sharib a. khan, mir suhail mohamad, syed gufran ahmad byhaqui & burhan aslam seer inc., redwood city, ca, usa aaron s. gajadhar, lucy williamson, purvi tandel, qiu yang, jessica chu, ryan w. benz, asim siddiqui & daniel hornburg element biosciences, san diego, ca, usa kelly blease, juan moreno, andrew boddicker, junhua zhao, bryan lajoie, andrew altomare, semyon kruglyak & shawn levy kbr, space biosciences division, nasa ames research center, moffett field, ca, usa ryan t. scott, rachel r. gilbert & san huei lai polo alamar biosciences inc., fremont, ca, usa ishara ariyapala, joanne beer & bingqing zhang nanostring technologies, seattle, wa, usa briana m. hudson, aric rininger & sarah e. church blue marble space institute of science, space biosciences division, nasa ames research center, moffett field, ca, usa afshin beheshti stanley center for psychiatric research, broad institute of mit and harvard, cambridge, ma, usa afshin beheshti harvard medical school and the wyss institute, boston, ma, usa george m. church national aeronautics and space administration, johnson space center, human health and performance directorate, biomedical research and environmental sciences division, houston, tx, usa scott m. smith & brian e. crucian university of texas medical branch, galveston, tx, usa sara r. zwart & anil s. menon department of biochemistry and molecular genetics, university of virginia, charlottesville, va, usa francine garrett bakelman department of medicine, division of hematology and oncology, university of virginia, charlottesville, va, usa francine garrett bakelman department of pharmacology, weill cornell medicine, new york, ny, usa qiuying chen, dawson miller & steven gross 10x genomics, pleasanton, ca, usa joe shuga, stephen williams & corey nemec bone and joint research laboratory, ottawa hospital research institute, ottawa, ontario, canada guy trudel department of medicine, division of physiatry, the ottawa hospital, ottawa, ontario, canada guy trudel department of cellular and molecular medicine, faculty of medicine, university of ottawa, ottawa, ontario, canada guy trudel department of biochemistry, microbiology, and immunology, university of ottawa, ottawa, ontario, canada martin pelchat department of biology, university of ottawa, ottawa, ontario, canada odette laneuville department of medicine, division of oncology, washington university school of medicine, st louis, mo, usa kelly l. bolton cell and molecular biology program, colorado state university, fort collins, co, usa susan m. bailey department of dermatology, weill cornell medicine, new york, ny, usa richard granstein cosmica biosciences inc., san francisco, ca, usa david furman stanford 1000 immunomes project, stanford school of medicine, stanford university, stanford, ca, usa david furman institute for research in translational medicine, universidad austral and conicet, buenos aires, argentina david furman department of neuroscience, king faisal specialist hospital and research centre, jeddah, saudi arabia bader shirah the feil family brain and mind research institute, weill cornell medicine, ny, usa christopher e. mason worldquant initiative for quantitative prediction, weill cornell medicine, new york, ny, usa christopher e. mason you can also search for this author 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scholar you can also search for this author in pubmed google scholar you can also search for this author in pubmed google scholar you can also search for this author in pubmed google scholar you can also search for this author in pubmed google scholar you can also search for this author in pubmed google scholar you can also search for this author in pubmed google scholar you can also search for this author in pubmed google scholar you can also search for this author in pubmed google scholar you can also search for this author in pubmed google scholar you can also search for this author in pubmed google scholar c.e.m., m.m. and j.m. conceptualized the study. c.e.m., e.g.o., c. meydan, s.m. and j.m. conducted the methodology. e.g.o., c.e.m., b.t.t., j. park, n.h., j. kim, i.m. and k.g. wrote the original draft of the manuscript. e.g.o., b.t.t., c. meydan, m.a. schmidt, m.b., j. kim, m.a. sierra, c.m.s., j.c.s., s.m.b., k.a.r. and b.s. reviewed and edited the manuscript. e.g.o., a.g.l., c. meydan, j. kim, n.h., j. park, b.t.t., s.g.m., k.s. and c.w. performed the visualization. c.e.m., j.m., a.s.m., e.g.o., e.e.a., c. mozsary and d.j.b. provided project administration. c.e.m., a.m.m., s.m.b., a.s.g., l.w., p.t., q.y., j.c., r.w.b., a. siddiqui, d.h., k.b., j.m., a. boddicker, j.z., b.l., a.a., s.k., s.l., i.a., j.b. and b.z. provided resources. c. meydan, a.g.l., b.t.t., j. kim, c.r.c., k.g., e.g.o., j. park, n.h., s.g.m., k.s., a. schweickart, t.m.n., e.c., j.f., s.a.n., s.s.t., c.b., s. levitte, c.l., d.p. and j. kim performed formal analysis. e.g.o., b.m.h., a.r., s.e.c., s.g., b.t.t., j. kim, n.d., d.n., k.a.r., j.w.h., l.p., r.k., v.o., e.d., s. lucotti, o.m., j.l., c. meydan, l.e.t., j. proszynski, f.g. b., a.s.k., s.r.z., b.e.c., s.m.s., a. beheshti, q.c., d.m., k.l.b., s.m.b., r.g., i.m., j. krumsiek, m.f.v., j.s., s.w., c.n., g.t., m.p., o.l. and d.f. conducted the investigation. e.g.o., j. kim, l.m.s., r.t.s., s.v.c., r.r.g., s. h.l.p., c.o.p., g.d., s.a.k., m.s., s.g.a.b. and b.a. curated the data. c.e.m., j.m., a.m.m., d.c.l., m.y., s.m.b., i.d.v., k.l.b. and g.m.c. acquired funding. c.e.m. supervised the study. all authors read and approved the final manuscript. correspondence to eliah g. overbey, cem meydan or christopher e. mason. b.t.t. is compensated for consulting with seed health and enzymetrics biosciences on microbiome study design and holds an ownership stake in the former. k.l.b. receives research funding from servier and bristol myers squibb, serves on the medical advisory board of goodcell. sc employee and is a shareholder at nanostring technologies. k.b., j.m., a. boddicker, j.z., b.l., a.a., s.k. and s.l. are employees of and have a financial interest in element biosciences. e.e.a. is a consultant for thorne healthtech. a.s.g., l.w., p.t., q.y., j.c., r.b., a. siddiqui and d.h. are employees of and have a financial interest in seer inc. and prognomiq inc. c. meydan is compensated by thorne healthtech. c.e.m. is co founder of cosmica biosciences. d.c.l. and i.m. receive research grant support/funding from atossa inc. r.g. is on the scientific advisory board of elysium health, is an advisor to gore range capital and is also an informal advisor to belletorus corporation, but has no financial ties to belletorus at this time. c.m.s., j.c.s. and m.a. schmidt hold shares in sovaris holdings llc. j. krumsiek holds equity in chymia llc, intellectual property in psyprotix and is co founder of iollo. m.y. is the founder and president of cantracer biosciences inc. the gc coi list is available at arep.med.harvard.edu/gmc/tech.html. a.m.m. has research funding from jannsen, epizyme and daiichi sankyo and has consulted for treeline, astrazeneca and epizyme. all other authors declare no competing interests. nature thanks jonathan goeke, jason locasale, jochen schwenk and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. peer reviewer reports are available. publisher’s note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. (a) prior human spaceflight omics study and sample counts with publicly available data, which is housed in osdr. (b) total number of sequence nucleic acid molecules in all prior studies (osdr, blue) compared to this study (inspiration4, red). (c) visualization of the different analysis paradigms used when analyzing the time series spaceflight data. the database identifier is provided as a shorthand to reference each comparison. computational pipelines for (a) 10x genomics multiome sequencing (snrna and snatac), (b) ont direct rna sequencing gene expression and m6a detection, (c) nanostring geomx whole transcriptome atlas profiling, (d) cfrna gene abundances, (e) t cell repertoire and b cell repertoire v(d)j immune profiling, (f) plasma processing for proteomic, metabolomic, and evp proteomic profiling, and (g) microbial profiling. (a) representative spatial imaging of skin biopsy tissue for each crew member (c001, c002, c003, and c004). processing was done in two batches and across four roi types. (b) umap projection of the rois. the colors represent roi types and shapes represent time points. most of the rois showed good clustering around roi types in both time points. (c) heatmap visualization of top variable genes across rois and time points in skin biopsies. (d) pca on scaled vst normalized counts of top 500 variable genes in cfrna data. (e) z score of vst normalized cfrna abundances from deseq2 (bh adjusted two sided p value < 0.01, |log2fc | > 1). total of 927 genes. (f) cfdna rna species elevated pre flight vs post flight. top 500 displayed for each group ranked by log2 fold change. (a) patterns of gene expression across seven time points and 13 comparisons. left: z scored log transformed normalized gene counts obtained from salmon (bottom left of each cell) and featurecounts (top right of each cell). right: log2(fold change) values obtained from edger (bottom left of each cell) and from deseq2 (top right of each cell). the genes are clustered by z scored log transformed normalized counts using the correlation distance metric. (b) patterns of base level m6a modifications across seven time points and 13 comparisons. left: z scored log transformed positional methylation probabilities obtained from m6anet. right: percentage of change in methylation between the conditions in each comparison, obtained from methylkit. the sites are clustered by the pattern of differential methylation across all comparisons using the correlation distance metric. on both panes (a) and (b), only the genes and sites with significant differences in expression and/or methylation in at least one comparison are plotted; the significance of individual comparisons is annotated with up and down arrows. (a) the number of degs in i4 flight profiles (fp1: grouped crew or individual crew members), i4 longitudinal profiles (lp3: grouped crew or individual crew members), and negative control groups (mock control day 2 vs day 1, mock control same day technical replicate differences, and i4 inter subject comparisons in preflight). all comparisons were done with downsampling to the same number of cells. intra timepoint subject comparisons are crew to crew comparison in the pre flight (l 92, l 44, l 3), immediately post flight (r + 1), and recovery (r + 45, r + 82) time intervals. the bars show the mean of the total number of degs, and error bars show the standard error for groups that have 3 or more comparisons summarized. (n = 4 independent subjects with 6 timepoints, and n = 1 control subject with 2 timepoints and 3 technical scrnaseq replicates for each timepoint.) (b) the number of total degs identified by deseq2 and pseudobulk counts in i4 flight profiles (fp1), i4 longitudinal profiles (lp3), and negative control groups (mock control day 2 vs day 1). all comparisons were done with aggregation into a single sample for each crew and each cell type. the bars show the mean of the total number of degs. (c) deg directionality heatmap represents the overlap of up regulated (orange) and down regulated (purple) degs across comparison groups (i4 timepoint comparisons, i4 individual variation, 10x negative controls). (d) heatmap representing the log2 fold change of i4 fp1 up regulated and down regulated pbmc degs in each comparison group (i4 timepoint comparisons, i4 individual variation, 10x genomics negative controls). (a) degs shared between the t cell and monocyte lineages for degs present in rp1, but not present in the fp1 profile. (b) overrepresented kegg pathways from deg sets unique to the rp1 profile in the t cell and monocyte lineages. the percent of pathways unique to each cell type are quantified along with the various configurations in which the pathway is shared between cell types and lineages. (a) log2 fold change of chromatin accessibility at promoters of genes that are differentially expressed in fp across different cell types. promoters are defined as the transcription start site ± 500 bp of a given gene. two sided p values were calculated by wilcoxon rank sum test. violin plots show the density of the points, and the center white dot represents the median, and the white line shows the range of the first and third quartiles. (b) directionality of delta z score for motif accessibility between flight profile fp1 and recovery profiles rp1 and rp2 for significant tf motifs of fp1 present in either rp1 or rp2. (c) heatmap of accessibility z score of top5 significantly increased and decreased tfs in each cell type in fp1. (d) heatmap of accessibility z score of top5 significantly increased and decreased tfs in each cell type in rp1. (e) heatmap of accessibility z score of top5 significantly increased and decreased tfs in each cell type in rp2. (a j) cvs for different microbial taxa from oral, forearm, nasal, gluteal crease, occiput, axillary vault, umbilicus, glabella, post auricular, and toe web space regions generated from skin swabs. cvs are calculated from both metagenomic and metatranscriptomic sequencing data. (a f) abundance standardized cvs for the human omics assays across pre flight, post flight, and recovery time intervals. the most variable analytes are labeled at the top of each violin plot. cv is calculated across n = 4 independent subjects in 6 to 7 timepoints for p = 16283, 8464, 527, 1765, 656, 203 analytes respectively from a to f. the center dot represents the median, and the black line shows the range of the first and third quartiles. (a) three different web portals were created: soma browser, single cell browser, and microbial browser. the soma browser includes (b) gene expression and protein abundance measurements in line chart and volcano plot formats, (c) log fold change calculations, and (d) comparison of degs across different contrasts, assays, studies, and organisms (statistical tests dependent on comparison, please see website). (e) the single cell browser enables visualization of cell type specific information, including gene co expression and atac seq region peak visualization. (f) the microbial browser includes microbial abundances across timepoints from different annotation databases for metagenomic and metatranscriptomic datasets (n = 4 independent subjects for 8 timepoints and 12 collection sites, or n = 9 environmental samples for 4 timepoints). the center of the boxplots represent the median, the box hinges encompass the first and third quartiles, and whiskers extend to the smallest and largest value no further than the 1.5x interquartile range (iqr) away from the hinges. this file contains supplementary figures 1 3, supplementary tables 4 and 9, supplementary note 1 and additional references. sample information. comprehensive list of samples collected from each crew member, at each timepoint, for each assay. tab 1 is an overview of which samples are present at each timepoint. tab 2 is an itemized list of each sample, including the number of sequenced dna/rna molecules for sequencing assays. osdr studies. comprehensive list of prior studies in osdr for previous assays on human, metagenomic, and metatranscriptomic samples. sequencing and mass spectrometry stats tables. sequencing and mass spectrometry statistics for multiome, tcr, bcr, cfrna, drna, and proteomics assays. cfrna calculations. tissue of origin analysis from cfrna sequencing. tab 1 contains fractions of cell type specific rna enrichment. tab 2 contains comparisons between timepoints. recovery profile pathways. overrepresented kegg pathways during recovery from spaceflight in pbmcs. tabs are split for cd4+ t cells, cd8+ t cells, cd14+ monocyte and cd16+ monocytes. metagenome and metatranscriptome cvs. species level cv calculations across crew members for metagenomic and metatranscriptomic samples from oral, nasal, and skin swab samples. human omics cvs. gene/analyte level cv calculations across crew members for nulisaseq, evp proteomic, plasma proteomic, metabolomic, drna seq and short read rna seq assays. gsea pathway enrichment is calculated for pre flight, post flight (r+1), and recovery time intervals. open access this article is licensed under a creative commons attribution 4.0 international license, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the creative commons licence, and indicate if changes were made. the images or other third party material in this article are included in the article’s creative commons licence, unless indicated otherwise in a credit line to the material. if material is not included in the article’s creative commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. to view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. reprints and permissions overbey, e.g., kim, j., tierney, b.t. et al. the space omics and medical atlas (soma) and international astronaut biobank. nature 632, 1145 1154 (2024). https://doi.org/10.1038/s41586 024 07639 y download citation received: 30 december 2022 accepted: 31 may 2024 published: 11 june 2024 issue date: 29 august 2024 doi: https://doi.org/10.1038/s41586 024 07639 y anyone you share the following link with will be able to read this content: sorry, a shareable link is not currently available for this article. provided by the springer nature sharedit content sharing initiative collection nature (nature) issn 1476 4687 (online) issn 0028 0836 (print) © 2025 springer nature limited sign up for the nature briefing newsletter   what matters in science, free to your inbox daily.

december 31, 2024e paper the hindu on books books of the week, reviews, excerpts, new titles and features. data point decoding the headlines with facts, figures, and numbers first day first show news and reviews from the world of cinema and streaming. health matters ramya kannan writes to you on getting to good health, and staying there the view from india looking at world affairs from the indian perspective. science for all the weekly newsletter from science writers takes the jargon out of science and puts the fun in! karnataka today your daily dose of news highlights from karnataka today's cache your download of the top 5 technology stories of the day. december 31, 2024e paper published   june 13, 2024 02:19 pm ist inspiration4 crew jared isaacman, sian proctor, hayley arceneaux, and chris sembroski chatting with st. jude patients from space in this handout photo released on september 17, 2021. | photo credit: reuters when pediatric cancer survivor hayley arceneaux and a trio of crewmates spent three days in space in 2021 as part of spacex's inspiration4 mission, they made history not only as the first all civilian team to orbit earth. they also provided the most in depth data on record regarding the effects of space travel on the human body. new research based on this data details changes in the brain, heart, muscles, kidneys and skin, immune regulation and stress levels and a breakdown in the activity of subcellular structures called mitochondria amid the microgravity environment, increased radiation and other factors in space. more than 95% of the biomarkers tracked in the research returned to preflight levels in the months after the crew returned to earth, though some abnormalities including in the mitochondria persisted, the researchers said. but the data indicated that spaceflights   at least short duration ones   do not pose significant health risks, they concluded. "we did not see anything that was worrisome, thankfully," said chris mason, a professor of physiology and biophysics at weill cornell medicine in new york who helped lead the research, with studies published on tuesday in nature and other journals. "this bodes well for other groups of civilians planning to live and work in space." "we did see some evidence of brain associated proteins in the blood after the mission, which we had also seen once before in the twins study (a 2019 study based on retired nasa astronauts and twins scott and mark kelly), and we think is evidence of brain stress during the mission," mason added. mason said this might be explained by findings in experimental mice flown to space that experienced disruptions in the blood brain barrier, a layer of cells protecting the brain. cognitive function in the inspiration4 crew, as measured by the university of pennsylvania's mathias basner, was not affected, mason noted. arceneaux, a physician assistant at st. jude children's research hospital in memphis and the mission's medical officer, and her crewmates   aerospace data engineer chris sembroski, geoscientist sian proctor and billionaire entrepreneur jared isaacman   were monitored before, during and after the flight. they underwent extensive testing and provided blood, saliva and other samples   including skin biopsies that left a lasting mark. "i love my space scar," said arceneaux, who was 29 at the time and became the youngest american to orbit earth, adding that the crew "really wanted to make a scientific impact." the research encompassed data from the two women and two men from inspiration4 as well as information from 64 astronauts who participated in longer stints aboard the international space station (iss) and other missions. inspiration4 flew at roughly 370 miles (590 km) above earth, higher than the iss, meaning the crew faced higher radiation levels. "so far, females seem to return to baseline (preflight status) faster than males, but our numbers are too small for this to be definitive," mason said. the onset of a "second space age" characterized by commercial missions has heightened the urgency to understand health risks, according to bioinformatician afshin beheshti of the blue marble space institute of science in seattle, another leader of the research. the amount of time spent in space is considered a key factor in the health effects, with greater concern over long duration missions. "the longer the duration in space, the greater the increase in health risks observed," beheshti said. beheshti said data from inspiration4 and japan's space agency, along with earth based experiments, detailed the significant impact of spaceflight on mitochondrial function and immune regulation. "previous publications have touched on these issues, but the new findings indicate that microgravity and space radiation systematically affect the body, leading to dysfunction at the cellular level that impacts multiple organs, including muscles, kidneys, heart, skin, and cns related (central nervous system) tissues," beheshti said. "the systemic response observed in spaceflight has been shown to contribute to increased frailty in humans. space is known to accelerate aging and many human diseases, and the research underscores this by identifying key health risks that can be targeted for countermeasures," beheshti added. the research pointed to potential paths to mitigate damage caused by space radiation. it found that certain molecules involved in regulating gene activity were inhibited in space. "this research demonstrates that targeting these key factors can rescue the immune and inflammatory pathways dysregulated in space," beheshti said. the researchers are taking a forward looking approach. "if humans are going to be living and working in space, or living on the moon and mars, we need to set a baseline data of metrics for how the body responds to space," mason said. published   june 13, 2024 02:19 pm ist astronomy / science (general) / science (general) copyright© 2024, thg publishing pvt ltd. or its affiliated companies. all rights reserved. back to top comments have to be in english, and in full sentences. they cannot be abusive or personal. please abide by our community guidelines for posting your comments. we have migrated to a new commenting platform. if you are already a registered user of the hindu and logged in, you may continue to engage with our articles. if you do not have an account please register and login to post comments. users can access their older comments by logging into their accounts on vuukle.

an official website of the united states government official websites use .gov a .gov website belongs to an official government organization in the united states. secure .gov websites use https a lock ( lock locked padlock icon ) or https:// means you've safely connected to the .gov website. share sensitive information only on official, secure websites. primary site navigation logged in as: it has not yet been peer reviewed by a journal. the national library of medicine is running a pilot to include preprints that result from research funded by nih in pmc and pubmed. corresponding author: chm2042@med.cornell.edu this work is licensed under a creative commons attribution noncommercial noderivatives 4.0 international license, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. the spacex inspiration4 mission provided a unique opportunity to study the impact of spaceflight on the human body. biospecimen samples were collected from the crew at different stages of the mission, including before (l 92, l 44, l 3 days), during (fd1, fd2, fd3), and after (r+1, r+45, r+82, r+194 days) spaceflight, creating a longitudinal sample set. the collection process included samples such as venous blood, capillary dried blood spot cards, saliva, urine, stool, body swabs, capsule swabs, spacex dragon capsule hepa filter, and skin biopsies, which were processed to obtain aliquots of serum, plasma, extracellular vesicles, and peripheral blood mononuclear cells. all samples were then processed in clinical and research laboratories for optimal isolation and testing of dna, rna, proteins, metabolites, and other biomolecules. this paper describes the complete set of collected biospecimens, their processing steps, and long term biobanking methods, which enable future molecular assays and testing. as such, this study details a robust framework for obtaining and preserving high quality human, microbial, and environmental samples for aerospace medicine in the space omics and medical atlas (soma) initiative, which can also aid future experiments in human spaceflight and space biology. our human space exploration efforts are at a unique transition point in history, with more crewed launches and human presence in space than ever before1. we can attribute this to the commercial spaceflight sector entering an industrial renaissance, with multiple companies forming collaboration and competition networks to send commercial astronauts into space. this recent evolution of human space exploration endeavors presents a valuable opportunity to accumulate more biological research specimens and improve our understanding of the impact of spaceflight on human health. this is critical since there is still much to learn about the varied biological responses to the spaceflight environment, characterized by microgravity and space radiation landscape2. the impact of spaceflight on human health includes musculoskeletal deconditioning3, cardiovascular adaptations4, vision changes5, space motion sickness6, neurovestibular changes7, immune dysfunction8, and increased risk of rare cancers9, among other changes2. however, we are still at the very beginning of the work to catalog biological responses to spaceflight exposure at the molecular resolution. prior work has characterized molecular changes that occur during spaceflight in astronauts. these include changes in cytokine profiles8,10,11, urinary albumin abundance12, and hemolysis13. furthermore, multi omic assays have provided genomic maps of structural changes in dna14 16, rna expression profiles11,17,18, sample wide protein measurements17,19,20, and metabolomic status17. additionally, international space station (iss) surfaces have been studied with longitudinal microbial profiles to track microbial pathogenicity and evolution to assess their potential influence on crew health21,22. to better improve our understanding of both human and microbial biology in space, it is critical that these analyses continue and expand as more spacecraft and stations are built and flown. combining and comparing work from prior missions in these new spacecraft and stations is especially important to overcome the small sample sizes and highlights a need for standardization between missions. in addition, recruiting large cohorts of astronauts is difficult, as the iss typically can only house up to six astronauts at a time. as of the time of writing, only 647 humans have been to space, starting with the launch of yuri gagarin in 1961. studies have spanned the vostok program, project mercury, the voskhod program, project gemini, project apollo, the soyuz program, the salyut space stations, mir, the space shuttle program, skylab, tiangong space station, and the iss. from the breadth of experiments that have been performed on the iss, only a minority have specifically been human research oriented23, and just a subset involve omics studies. the nasa twin study created the most in depth multi omic study of astronauts prior to inspiration4, but was limited to one astronaut and one ground control17. all of these factors have limited the statistical power of astronaut omic experiments and increase the difficulty of providing robust scientific conclusions. standardizing biospecimen collections across multiple missions will create larger sample sets needed to draw these conclusions. here, we establish the standard biospecimen sample collection and banking procedures for the space omics and medical atlas (soma). a key goal of soma is to standardize biospecimen collection and processing for spaceflight, to generate high quality multi omics data across spaceflight investigations. this paper provides sample collection methods built for standardized collections across different crews and missions. these can generate harmonized datasets with greater statistical power and thus increase our scientific return yields from spaceflight investigations. we also present metrics on sample collection yields, instances of prior astronaut sample collection in scientific literature, and considerations for improvement of sample collection on future missions based on crew feedback. in its inaugural use case, these samples were collected from the inspiration4 (i4) astronaut cohort and are currently in use for several other missions (polaris dawn, axiom 2), which will enable continued utilization for future crewed space missions. we formulated and executed a sampling plan that spans a wide range of biospecimen samples: venous blood, capillary dried blood spots (dbss), saliva, urine, stool, skin swabs, skin biopsies, and environmental swabs (fig 1a). the collection of various types of samples covered the scope of previous assays on astronaut samples (table 1), but also enabled newer omics technologies, such as spatially resolved, single molecule, and single cell assays. (a) list of biospecimen samples collected over the course of the study. (b) timepoints for each biospecimen sample collection. “l−” denotes the number of days prior to launch. “r+” denotes the number of days after return to earth. “fd” denotes which day of the flight a sample was collected. (c) location of each collection timepoint. prior biospecimen collections from astronauts. listed studies are limited to the past decade. for the inspiration4 mission, sample collection spanned three time points pre launch (l 92, l 44, l 3 days), three time points during flight (flight day 1 (fd1), fd2, fd3), and four time points post return (r+1, r+45, r+82, r+194 days). venous blood, urine, stool, and skin biopsies were collected during ground timepoints only, while capillary dbss, saliva, and skin swabs were collected both on the ground and during flight (fig 1b). environmental swabs of the dragon capsule were collected pre flight in the crew training capsule and during flight in the spacecraft launched from cape canaveral (fig 1b). samples were collected across a variety of locations based on the crew’s training and travel schedule. l 92 and l 44 were collected in hawthorne, ca at spacex headquarters, l 3 and r+1 were collected at cape canaveral, fl at a facility near the launch site. fd1, fd2, and fd3 were collected inside the dragon capsule while in orbit. r+45 was collected at the crew members’ individual locations (which spanned the us states ny, nj, tn, and wa), r+82 was collected at weill cornell medicine, ny and r+194 was collected at baylor college of medicine, tx (fig 1c). blood was collected using a combination of venipuncture tubes to collect venous blood and contact activated lancets to collect capillary blood from the fingertip. each crew member provided blood samples, collected into one blood rna tube (brna), four k2 edta tubes, two cell preparation tubes (cpts), one cell free dna tube (cfdna bct), one serum separator tube (sst), and one dried blood spot (dbs) card per time point. from these tubes, whole blood, plasma, pbmcs, serum, and cell pellet samples were collected (table 2). sample yields are reported below. samples were aliquoted for long term storage and biobanking (table 3). blood derivative allocations. samples types collected, their tube type of origin, and assay allocation. samples collected in excess were biobanked to enable additional experiments as new assays are developed. blood derivative aliquot parameters. plasma, serum, and pbmcs aliquots were created for downstream assays that only require a portion of the total sample collected in order to minimize freeze thaw cycles. brna tubes were collected in order to isolate total rna using the paxgene blood rna kit (fig 2a). yield ranged from 3.04 14.04 μg/tube of total rna across all samples and the rna integrity number (rin) ranged from 3.2 8.5 (mean: 6.95) (fig 2b). rna was stored at −80°c after extraction. the collection of total rna enables a variety of downstream rna profiling methods. it will allow comparative studies to prior rna sequencing performed on astronauts, particularly snorna & lncrna biomarkers analyzed from space shuttle era blood25,32, mrna & mirna measured during the nasa twin study17,18, and whole blood rna arrays from the iss33. additionally, rna yields are more than sufficient to perform direct rna sequencing using oxford nanopore technologies (ont) platforms, which require 500 ng of total rna per library (manufacturer’s protocol, ont kit sqk rna002). this enables the study of rna modification changes during spaceflight to create epitranscriptomic profiles for the first time in astronauts. (a) one 2.5ml brna tube was collected per crew member at each ground timepoint. (b) brna tube total rna yields per sample (μg) and rins. (c) four k2 edta tubes were collected per member at each ground timepoint. one tube was used for a cbc, one tube was used to isolate evps, and two tubes were used for isolation of pbmcs. (d) plasma and evp yields from the “[2] evps” tube on figure 2c. (e) pbmc yields per ml from the “[3] pbmcs” tubes on figure 2c. four k2 edta tubes were drawn at each timepoint from each crew member (fig 2c). one k2 edta tube was submitted to quest diagnostics to perform a complete blood count (cbc, quest test code: 6399). one tube was used to isolate extracellular vesicles and particles (evps) for proteomic quantification (fig 3a). total evp quantities varied from 2.71 28.27 ug (fig 2d). two k2 edta tubes were used to isolate pbmcs for single cell sequencing (10x chromium single cell multiome atac + gene expression and chromium single cell immune profiling workflows). after collection, a ficoll separation was performed to isolate pbmcs, which ranged from 340,000 975,000 cells per ml of blood (fig 2e). one prior single cell gene expression experiment, nasa twin study, was performed on astronauts, which found immune cell population specific gene expression changes and a correlation with microrna signatures11,18. centrifuge (brown circles) and aliquoting (white and green boxes and circles) protocols for (a) k2 edta tubes designated for evp isolation (b) cpts (c) cfdna bcts and (d) ssts. additional pbmcs, plasma, and serum were collected from cpts (fig 4a), cfdna bcts (fig 4d), ssts (fig 4c), as well as red blood cell pellets. cpts were spun and aliquoted according to the manufacturer’s instructions (fig 3b). plasma volume per tube ranged from 3000 14,000 ul per tube (fig 4d). there were a few instances were cpt tubes shattered in the centrifuge and plasma could not be salvaged. plasma can be used to validate or refute previous studies, including cytokine panel10,26, exosomal rna seq25,32, extracellular vesicle microrna30, and proteomic20,27 29 results. pbmcs were also collected, aliquoted into 6 cryovials per cpt, and stored in liquid nitrogen after slowly cooled in a mr. frosty to −80°c. these can be used to follow up on previous studies on adaptive immunity, cell function, and immune dysregulation8,31,41 43. the remaining red blood cell pellet mixtures from below the gel plug in each cpt tube were stored at −20°c. (a) a spun cpt yields plasma, pbmcs, and a red blood cell pellet. pbmc from each tube were divided into 6 cryovials and viably frozen. plasma was aliquoted and the pellet was frozen at −20c. (b) a spun cfdna bct yields plasma and a red blood cell pellet. plasma was purified with an additional spin (see fig 4a) then aliquoted. the pellet was frozen at −20c. (c) a spun sst yields serum and a red blood cell pellet. serum was aliquoted and the pellet was frozen at −20c. (d) cpt plasma volumes per timepoint are reported. (e) cfdna bct plasma volumes per timepoint. (f) sst serum volumes per timepoint. an extra tube was drawn for c004 at r+45, resulting in a higher serum yield. cfdna bct tubes were collected to isolate high quality cfdna from plasma. cfdna bcts were spun and aliquoted according to the manufacturer’s instructions (fig 3c). the remaining cell pellet mixture was frozen at −20°c. plasma volume per timepoint ranged from 1500 5000 ul (fig 4e). 500 ul aliquots were frozen at −80°c. cfdna extracted from these tubes can be analyzed for fragment length, mitochondrial or nuclear origin, and cell type or tissue of rigin24,58. the sst was spun and aliquoted according to the manufacturer’s instructions (fig 3d). serum volume ranged from 2000 8000 ul per timepoint (fig 4f). similar to plasma, serum can be allocated for cytokine analysis and can also be used to perform comprehensive metabolic panels, including one we used at quest (cmp, quest test code: 10231) for metrics on alkaline phosphatase, calcium, glucose, potassium, and sodium, among other metabolic markers. the remaining cell pellet mixture from each sst tube was stored at −20°c. in addition to venous blood, capillary blood was collected onto a dbs card using a contact activated lancet pressed against the fingertip (fig 5a). capillary blood was collected onto a dried blood spot (dbs) card to preserve nucleic acids and proteins. the amount of capillary blood collected across timepoints varied (fig 5b, 5c) according to how much blood could be collected before the puncture wound closed. (a) dried blood spot cards were collected preflight, during flight, and postflight. there were five spots for blood collection per card. (b) blood collections varied in saturation level across blood spots and timepoints. these were classified as “full”, “partial”, and occasionally “empty”. (c) dbs card yields per blood spot, per timepoint, and per crew member. saliva was collected at the l 92, l 44, l 3, fd1, fd2, fd3, r+1, r+45, and r+82 timepoints using two methods. first, saliva was collected using the omnigene oral kit, which preserves nucleic acids (fig 6a) during the ground timepoints. from these samples, dna, rna, and protein were extracted. dna yield ranged from 28.1 to 3,187.8 ng, rna yield from 396.0 to 3544.2 ng (less the two samples had concentrations too low for measurement), and protein concentration from 92.97   93.15 ng. (a) dna, rna, and protein yields from the omnigene oral kits. (b) volume of crude saliva collected per timepoint. second, crude saliva (i.e. saliva with no preservative added) was collected into a 5ml dnase/rnase free screw top tube during the ground and flight timepoints. saliva volume varied from 150   4,000 ul per tube (fig 6b). crude saliva was also collected during flight (fd2 and fd3), in addition to the ground timepoints. saliva collections have been conducted throughout spaceflight studies for assessing the immune state, particularly in the context of viral reactivation. previously identified viruses that reactivate during spaceflight include epstein barr, varicella zoster, and cytomegalovirus 46. responses to reactivation of these viruses can be asymptomatic, debilitating, or even life threatening, thus assessing these adaptations is beneficial in understanding viral spaceflight activity as well as crew health. in addition to viral nucleic acid quantification, numerous biochemical assays can also be performed, including measurements of c reactive protein (crp), cortisol, dehydroepiandrosterone (dhea), and cytokines, among others 10,35,44,46. urine was collected in sterile specimen cups at the l 92, l 44, l 3, r+1, r+45, and r+82 timepoints. specimen cups were collected 1 2 times per day. for preservation, urine was aliquoted and stored at −80°c. half the urine had zymo urine conditioning buffer (ucb) added before freezing, to preserve nucleic acids. samples yielded 23   155.5 ml of crude urine and 21   112 ml of ucb urine per specimen cup (fig 7a). urine was split into 1 ml   15 ml aliquots before freezing at −80°c. (a) urine volumes per timepoint. volumes are reported for both crude urine and urine preserved with zymo urine conditioning buffer (ucb). (b) timepoints that stool tubes were collected. “gut” tubes are omnigene•gut tubes for microbiome preservation. “met” tubes are omnimet•gut tubes for metabolome preservation. (c) stool “gut” tube dna and rna extraction quantities. a wide variety of assays can be performed on urine samples. previous studies have included viral reactivation40,44,46, urinary cortisol47,55, iron and magnesium measurements49,52, bone status50,51,53,56, kidney stones50,51, proteomics11, telomere measurements59, and various biomarkers and metabolites17,55. stool was collected at the l 92, l 44, r+1, r+45, and r+82 timepoints. stool samples were stored into two collection containers at each timepoint, one dna genotek omnigene gut (omr 200) kit with a preservative for metagenomics and another (me 200) with a preservative for metabolomics (fig 7b). stool was the least consistent sample collected due to the limited windows available for sampling during collection timeframes. dna and rna were extracted from aliquots of the omnigene gut (omr 200) tubes for downstream microbiome analysis. dna yield ranged from 358.5   16,660 ng, rna from 690   2010 ng (fig 7c). large variations in yield are attributable to variable stool mass collected between kits. stool samples enable various biochemical, immune, and microbiome changes studies. previous metagenomic assays have found that shannon alpha diversity and richness during long duration missions to the iss 39. body swabs were collected at all timepoints. samples were collected by swabbing the body region of interest for 30 seconds, then placing the swab in a sterile 2d matrix tube (thermo scientific #3710) with zymo dna/rna shield preservative. for the first two swab locations, the oral and nasal cavity, the swab was placed directly on the body after removal from its sterile packaging (dry swab method; fig 8a). for the remaining body locations, the swab was briefly dipped in nuclease free, dna/rna free water before proceeding (wet swab method). eight distinct sites were swabbed with the wet swab method: post auricular, axillary vault, volar forearm, occiput, umbilicus, gluteal crease, glabella, and the toe web space (fig 8b). the astronaut microbiome has previously been studied in the forehead, forearm, nasal, armpit, navel, postauricular, and tongue body locations, and changes have been documented during flight. changes in alpha diversity and beta diversity were documented, as well as shifts in microbial genera39. however, the impact of these changes on skin health and immunological health are not well understood. (a) dry swabs were collected from two body locations. (b) wet swabs were collected from eight body locations. (c) swabs were collected from the deltoid region. immediately after, 3  or 4 mm skin biopsies were collected from the same area and divided for histology and spatially resolved transcriptomics. acquiring extensive swab samples from the crew skin allows for characterization of the habitat environment, crew skin microbiome adaptations, and interactions with potential human health adaptations resulting from spaceflight exposure. this is very relevant for crew health, considering astronauts become more susceptible to infections during spaceflight missions63, with the relationship between microbe host interactions from spaceflight exposure, which may be a causative factor of astronauts immune dysfunction, which is still not well understood. a skin biopsy on the deltoid was obtained from the l 44 and r+1 timepoint. biopsies were also collected in advance of a flight to ensure the biopsy site is fully healed before the flight so there is no risk of complication.the wet swab method was used to collect the skin microbiome before the skin biopsy. the skin biopsies were three millimeters in diameter and were collected for histology and spatially resolved transcriptomics (srt) (fig 8c). one third of the sample was stored in formalin and kept at room temperature to perform histology. the remaining two thirds of the sample was stored in a cryovial and placed at −80°c for srt (fig 8c). this is the first sample collected from astronauts for spatially resolved transcriptomics. the skin is of high interest due to the inflammation related cytokine markers such as il 12p40, il 10, il 17a, and il 1810,17 and skin rash’s status as the most frequent clinical symptom reported during spaceflight64. environmental swabs were collected in flight during the f1 and f2 timepoint. additionally, environmental swabs were collected from the flight simulation capsule at spacex headquarters after days of crew training during the l 92 and l 44 timepoints. environmental swabs were collected using the wet swab method. ten environmental swabs were collected per time point at the following locations in the capsule: an ambient air/control swab, the execute button, the viewing dome, the side hatch mobility aid, the lid of the waste locker, the head section of one of the seats, the commode panel, the right and left sides of the control screen, and the g meter button (fig 9a d). additionally, the spacecraft’s high efficiency particulate absorbing (hepa) filter was acquired post flight (fig 10a). this filter was cut into 127 rectangular pieces (1.2” × 1.6” × 4”) and stored at −20°c (fig 10b, fig 10c). (a) swab locations, descriptions, and label ids. (b) interior view of the spacex dragon capsule. (c) view of the control panel located above the middle seats in the dragon capsule. (d) view of the cupola (viewing dome) region from the outside. the rim of the dome was swabbed from the inside (id 10). (a) view of the un cut hepa filter. (b) hepa filter during sectioning. (c) cutting schema for the hepa filter. the filter was split into 21 columns and 7 rows, creating a total of 147 preserved sections. previous microbial profiling of spacecraft environments has revealed that equipment sterilized on the ground becomes coated in microbial life in space due to interactions with crew and the introduction of equipment that has not undergone sterilization65. subsequent microbial monitoring assays performed on the iss have detected novel, spaceflight specific species on the iss66. once in space, surface microbes are subject to the unique microgravity and radiation environment of flight, which will influence evolutionary trajectory. the potential impact of this influence on pathogenesis is a concern for long duration space missions, especially given that changes in host pathogen interactions may also be affected during spaceflight67. we report here on biospecimen samples collected from the spacex i4 mission, the most comprehensive human biological specimen collection effort performed on an astronaut cohort to date. the extensive archive of biospecimens included venous blood, dried blood spot cards, saliva, urine, stool, microbiome body swabs, skin biopsies, and environmental capsule swabs. the study objective was to establish a foundational set of methods for biospecimen collection and banking on commercial spaceflight missions suitable for multi omic and molecular analysis. biospecimens were collected to enable comprehensive, multi omic profiles, which can then be used to develop molecular catalogs with higher resolution of human responses to spaceflight. select, targeted measures in clinical labs (clia) were also performed immediately after sample collection (cbc, cmp), and samples and viable cells were preserved in a long term cornell aerospace medicine biobank, such that additional assays and measures can be conducted in the future. there are several reasons why rigorous biospecimen collection methods for commercial and private spaceflight missions must be developed, which are scalable and translational across populations, missions, and mission parameters. first, little is known about the biological and clinical responses that occur in civilians during and after space travel. while professional astronauts are generally young, healthy, and extensively trained, civilian astronauts have been, and likely will be, far more heterogeneous. they will possess a variety of phenotypes, including older ages, different health backgrounds, and greater medication use, and may experience different medical conditions, risks, and comorbidities. careful molecular characterization will be beneficial for the development of appropriate baseline metrics and countermeasures and, therefore, beneficial for the individual spaceflight experience. in the future, such analyses may enable precision medicine applications aimed at optimizing countermeasures for each individual astronaut who enters and returns safely from space68,69. second, multi omic studies inherently present a large number of measurements within a small set of subjects. these high dimensional datasets present numerous potential challenges with regard to amplification of noise, risk of overfitting, and false discoveries70. at all times, scientists engaged in multi omic analyses must take special care that true biological variance is what has been measured. the introduction of experimental variance through the progression from sample collection, transport, storage, to sequencing and analysis can introduce artifacts of variance that render the detection of true biological variance and interpretation of results more difficult. for this reason, tight adherence to experimental controls or annotation at every step of the experimental condition is crucial. careful annotation allows for the assignment of class variables in post hoc analysis. among such applications are the attempt to detect batch effects or determine the impact of variations in temperature (collection, storage, or transport)71. the necessary means to address experimental variance are longitudinal sampling and specimen aliquoting. longitudinal sampling (i.e. collecting numerous serial samples from each test condition) from pre flight, in flight, and post flight allows for greater statistical power when assessing changes attributable to spaceflight. in addition, each sample collected should be divided upon collection into multiple aliquots. this better assures that freeze thaw cycles can be avoided in the analysis stage, as freeze thaw events can introduce considerable experimental variance depending on the molecular class being measured. maintaining all samples at their optimal storage temperature at all times, typically −80°c or lower, is crucial72. special attention must be given to how the collection and storage methods in flight vary in relation to the conditions on earth. spaceflight presents considerable differences in the operating environment, where ground conditions are far easier to control than flight. in practice, this may limit the types of samples that can be collected during flight. third, rigorous methods must be developed and followed to pursue comparisons across missions with varying design parameters. in this consideration, there is an argument for the development of specimen collection, transport, storage, processing, analysis, and reporting standards. at the same time, this must be balanced with the flexibility required for innovation since standards can sometimes limit advancement in methodology. in the present study, common methods were used for the inspiration4 and the forthcoming polaris dawn and axiom missions. however, selected methods may require optimization for polaris dawn to increase the yields during sample processing and adapt to unique parameters imposed by the anticipated spacewalk (extravehicular activity; eva). moreover, within standards or best practices, unique research for each mission may require alteration of previously successful methods. with these considerations in mind, we must balance methodology standardization with advances in methodology options and mission specific objectives. as the commercial spaceflight sector gains momentum and more astronauts with different health profiles and backgrounds have access to space, comprehensive data on the biological impact of short duration spaceflight is of paramount importance. such data will further expand our understanding and knowledge of how spaceflight affects human physiology, microbial adaptations, and environmental biology. the use of integrative omics technologies for civilian astronauts will unveil novel data on genomics, proteomics, metabolomics, and transcriptomics. creating multi omic datasets from spaceflight studies on astronaut cohorts will further advance our understanding, inform future mission planning, and help discover what appropriate countermeasures can be developed to minimize future risk and enhance performance. validating sample collection methodologies initially in short duration commercial spaceflight is a key step for future human health research in long duration and exploration class missions to the moon and beyond. to help meet these challenges, we have established the soma protocols, which detail standard multi omic measures of astronaut health and protocols for sample collection from astronaut cohorts. although the all civilian inspiration4 crew pioneered the first use of the soma protocols, the methodology outlined here is robust and generalizable, making it applicable to future astronaut crews from any commercial mission provider (e.g., spacex, axiom space, sierra space, blue origin) or space agencies (nasa, esa, jaxa, roscosmos). furthermore, the soma banking, sequencing, and processing methods are a springboard for continuing biospecimen analysis and expanding our knowledge of multi omic dynamics before, during, and after human spaceflight missions, providing a molecular roadmap for crew health, medical biometrics, and possible countermeasures. venipuncture was performed on each subject using a bd vacutainer® safety lok™ blood collection set (bd biosciences, #367281) and a vacutainer one use holder (bd biosciences, 364815). the puncture site was located near the cubital fossa and was sterilized with a bzk antiseptic towelette (dynarex, reorder no. 1303). blood was collected into 1 serum separator tube (sst, bd biosciences: #367987, lot: #1158449, #1034773), 2 cell processing tubes (cpt, bd biosciences: #362753, lot: #1133477, #1012161), 1 blood rna tube (brna, paxgene: #762165, lot: #1021333), 1 cell free dna bct (cfdna bct, streck: #230470, lot: #11530331), and 4 k2 edta blood collection tubes (bd biosciences, #367844, lot: #0345756) per crew member per time point. for samples collected in hawthorne, blood was drawn at spacex headquarters, then immediately transported to usc for processing. samples collected at cape canaveral were processed on site. for processing, serum separator tubes (sst) were centrifuged at 1300xg for 10 minutes. 500ul aliquots of serum were aliquoted into 1ml matrix 2d screw tubes (thermofisher, 3741 wp1d br) and stored at −80°c. sst tubes were recapped and stored at −20°c to preserve the red blood cell pellet. cell processing tubes were centrifuged at 1800×g for 30 minutes. plasma was aliquoted into 1ml matrix 2d screw tubes and stored at −80°c. 5ml of 2% fbs (thermofisher, #26140079) in pbs (thermofisher, #10010023) was added to the cpt tube to resuspend pbmcs. pbmc suspension was transferred to a clean 15ml conical tube. the total volume was brought to 15ml with 2% fbs in pbs. the tube was centrifuged for 15 minutes at 300×g. supernatant was discarded. pbmcs were resuspended 6ml of 10% dmso (millipore sigma, #d4540 500ml) in fbs. 1ml of pbmcs were moved to 6 cryogenic vials (corning, #8672). cryovials were placed in a mr. frosty™ (thermofisher, #5100 0001) and stored at −80°c. cpts were recapped and stored at −20°c to preserve the red blood cell pellet. cell free dna blood collection tubes (cfdna bcts) were centrifuged at 300×g for 20 minutes. plasma was transferred to a 15ml conical tube. plasma was centrifuged 5000×g for 10 minutes. 500ul aliquots of plasma were aliquoted into 1ml matrix 2d screw tubes and stored at −80°c. cfdna bcts were recapped and stored at −20°c to preserve the red blood cell pellet. paxgene blood rna tubes were processed according to the manufacturer’s instructions. briefly, tubes were left upright for a minimum of 2 hours before freezing at −20°c. for rna extraction, tubes were thawed and processed with the paxgene blood rna kit (qiagen, #762164). one 4ml k2 edta tube was shipped on ice overnight to wcm for processing. blood was centrifuged at 500 × g for 10 minutes, then plasma was transferred to a new tube and centrifuged at 3000 × g for 20 minutes, and the supernatant was collected and stored at −80°c for evp isolation. plasma volumes ranged between 0.6   1.7 ml. plasma was later thawed for downstream processing, when concentrations were measured. plasma samples were thawed on ice and evps were isolated by sequential ultracentrifugation, as previously described (hoshino et al., 2020). briefly, samples were centrifuged at 12,000 × g for 20 minutes to remove microvesicles, then evps were collected by ultracentrifugation in a beckman coulter optima xe or xpe ultracentrifuge at 100,000 × g for 70 minutes. evps were then washed in pbs and pelleted again by ultracentrifugation at 100,000 × g for 70 minutes. the final evp pellet was resuspended in pbs. crew members warmed their hands and massaged their finger towards the fingertip to enrich blood flow towards the puncture site. the puncture site was sterilized using a bzk antiseptic towelette (dynarex, reorder no. 1303). skin was punctured using a contact activated lancet (bd biosciences, #366593) or a 21 gauge needle (bd biosciences, #305167), depending on crew member preference. capillary blood was collected onto the whatman 903 protein saver dbs cards (cytiva, #10534612). blood was transferred by touching only the blood droplet to the surface of the dbs card. dbs cards were stored at room temperature with a desiccant pack (cytiva, #10548239). to collect crude saliva, crew members uncapped and spit into a sterile, pcr clean, 5ml screw cap tube (eppendorf, 30122330). crew spit repeatedly until at least 1ml was collected. saliva was transported to a sterile flow hood and separated into 500ul aliquots. aliquots were frozen at −80°c. to collect preserved saliva, crew members used the omnigene oral kit (dna genotek, ome 505). crew members spit into the kit’s tube until they reached the fill line. the tube was re capped, which released the preservative liquid. tubes were inverted to mix the saliva and preservative before being placed at −20°c for storage. after all timepoints were collected, dna, rna, and protein were extracted using the allprep dna/rna/protein kit (qiagen, #47054). sample concentrations were measured with qubit high sensitivity dsdna and rna platform. proteins were quantified with the pierce™ rapid gold bca protein assay kit (thermo scientific, #a53225) on promega glomax plate reader. crew members urinated into sterile specimen containers (thermo scientific, #13 711 56). the container was stored at 4c until it was prepared for long term storage. to prepare urine samples for long term storage, urine was aliquoted into 1ml, 15ml, and 50ml tubes. half of the urine was immediately placed at −80°c. the other half had urine conditioning buffer (zymo, #d30611 140) added to the sample before placing in the −80°c freezer. crew members isolated a stool sample using a paper toilet accessory (dna genotek, om ac1). stool was transferred into and omnigene•gut tube (dnagenotek, omr 200) and an omnimet•gut tube (dna genotek, me 200). tubes were placed at −80°c for long term storage. for nucleic acid extraction, 200ul of each tube was allocated for dna extraction with the qiagen powerfecal pro kit and 200ul was allocated to rna extraction with the qiagen powerviral kit. the remaining sample was split into 500ul aliquots and re stored at −80°c. crew members put on gloves and remove a sterile swab from its packaging. for collection of the postauricular, axillary vault, volar forearm, occiput, umbilicus, gluteal crease, glabella, toe web space, and capsule environment regions, swabs were dipped in nuclease free water (this step was skipped for oral and nasal swabs) for ground collections. for in flight collections, hfactor hydrogen infused water was used in place of nuclease free water. each body location was swabbed for 30 seconds, using both sides of the swab. swabs were then placed in 1ml matrix 2d screw tubes containing 400ul of dna/rna shield (zymo). the tip of the swab was broken off so that only the swab tip was stored in the matrix 2d screw tube. tubes were stored at 4c. skin biopsies were performed on the deltoid region of the arm. each site was prepared by application of chloraprep and anesthesia was induced with administration of 1% lidocaine with 1:100,000 epinephrine. a trephine punch was used to remove a 3  or 4 mm diameter piece of skin. the resected piece was cut into approximately ⅓ and ⅔ sections. the smaller piece was added to a formalin filled specimen jar. the larger piece was placed in a cryovial and stored at −80°c. surgical defects were closed with 1 or 2 5 0 or 4 0 nylon sutures. hepa filter was taken apart and sectioned under a chemical hood to avoid contamination. the filter contained two parts, an activated carbon component and a hepa filter. the activated carbon component was discarded and the filter was sectioned using a sterile blade. sections were placed in individual specimen containers and stored at −20°c. all subjects were consented and samples were collected and processed under the approval of the irb at weill cornell medicine, under protocol 21 05023569. figures were generated using adobe illustrator and biorender. plots were generated in r using ggplot2. spacex dragon capsule images are from the spacex flickr account (https://www.flickr.com/people/spacex/). we thank the scientific computing unit (scu) at wcm and the genomics, epigenomics, and biorepository cores, the nih (r01mh117406) and nasa (nnx14ah50g, nnx17ab26g, 80nssc22k0254, nnh18ztt001n fg2, nnx16ao69a, 80nssc23k0832), the lls (mcl7001 18, lls 9238 16, 7029 23), as well as igor tulchinsky and the worldquant foundation, the gi research foundation (girf), the radvinsky/chudnovsky family. we thank jj hastings for early protocol work. jk thanks mogam science foundation. we also thank jennifer conrad for cpt photography. articles from biorxiv are provided here courtesy of cold spring harbor laboratory preprints connect with nlm national library of medicine 8600 rockville pike bethesda, md 20894

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solicitations and happenings. connect with us nasa funded research institute seeks space health postdoctoral fellows aug. 29   trish announced it is seeking proposals for its 2025 class of postdoctoral fellows. read the announcement. nasa funded research institute selects new class of space health fellows aug. 16   trish announced its selections for the institute’s 2024 postdoctoral fellowship, a space health program intended to launch the careers of a new generation of researchers tackling various challenges involved with human space exploration. read the release. trish selects projects to advance the readiness of medication production in deep spacejune 27   trish announced two selected projects to analyze advanced engineering and synthetic biology solutions that can be used in long duration, deep space human missions. read the release. trish shares new health data from first all civilian orbital space missionjune 11   in a new paper published in nature, trish and its collaborators present spaceflight health data captured from the first all civilian orbital spaceflight mission in history. read the release. trish announces selection for ship solicitationmay 9   trish announced its first selection for the space health ingress program (ship) solicitation. read the release. trish seeking scientist proposals to advance space health research dec. 18   trish is seeking innovative proposals for projects that recruit and engage researchers new to space biomedical research. selected proposals will receive a partnership grant as part of the space health ingress program (ship). read the announcement. bcm, australian antarctic division announce agreement to advance collaboration in space health research nov. 30   a new agreement between trish and the australian antarctic division will enable a new international collaboration for scientific research and discovery in the field of space health to better understand human resilience and behavioral health in remote and isolated environments resembling the challenges of spaceflight. read the announcement. trish to study spaceflight effects on genome and nervous system on axiom space's ax 3 missionnov. 28   trish will conduct a suite of human health and performance research projects during axiom space’s upcoming axiom mission 3 (ax 3) to the international space station (iss), scheduled to launch in 2024. read the announcement. trish selects healthcare and data management projects for spaceflightsnov. 1   trish announced two new projects with ejenta and trialx to develop systems to improve healthcare delivery and data management for spaceflight participants and researchers. trish calls for postdoctoral proposals for fellowship programoct. 4   trish announced it is seeking proposals for its postdoctoral fellowship program, which supports early career scientists pursuing research with the potential to reduce the human health risks associated with spaceflight. trish selects 2023 class of space health postdoctoral fellowsjuly 18   trish announces its selections for the trish 2023 fellowship cohort of postdoctoral researchers. read the announcement. baylor, korea national institute of health collaborate to further space health researchapril 27   a new agreement between baylor college of medicine’s center for space medicine and the korea national institute of health (knih) will enable new international collaboration for scientific research and discovery in the field of space health. trish seeking proposals for data transfer technology for space healthapril 6   trish announced it is seeking proposals for developing a health and research data management platform for humans journeying into space. trish research on axiom's ax 2 mission to examine effects of spaceflight on humansmarch 20   trish announced several human health and performance research projects to be conducted aboard axiom mission 2 (ax 2) to the international space station (iss). trish selects two projects to advance human space health research through cellular repairnov. 21   trish announced its selection of two projects that will protect astronaut health by enhancing pre existing cellular repair. the awards are part of trish’s biomedical research advances for space health solicitation. trish sends human health experiments aboard polaris dawn missionnov. 2   trish will send a series of human health research experiments aboard the upcoming polaris dawn mission, the first in a series of human spaceflight missions from the polaris program. read the announcement. polaris dawn selects 38 science and research experiments to advance human health and space explorationoct. 24   polaris dawn announced the selection of research for the mission, including many trish sponsored projects. trish fellowship seeks to train space health scientistssept. 29   trish announced a fellowship opportunity for postdoctoral scientists tackling the challenges of deep space exploration. read the release. trish awards three postdoctoral fellowships to further space health researchjuly 7   trish announced the new fellowship cohort of postdoctoral researchers supported by the trish academy of bioastronautics. read the release. trish releases space health documentary and resourcesmay 23   trish releases the space health: surviving in the final frontier documentary, exploring the health challenges of human spaceflight. the film features astronauts, scientists, and innovators all working to keep humans healthy in space. read the release. axiom space ax 1 mission to expand health, technology researchers’ access to the issmarch 17   trish adds the ax 1 crew members’ biomedical data to the institute’s expand database to help further human exploration in space. read the release. trish to enhance research on ax 1 mission, data on human spaceflight impactsmarch 3   trish will sponsor important human health and performance research on the ax 1 mission, the world’s first all private astronaut mission to the international space station. read the release. trish names space medicine veteran as chief scientific officerfeb. 22   the translational research institute for space health at baylor college of medicine with consortium partners, caltech and the massachusetts institute of technology, announces the addition of jennifer fogarty, ph.d., as the institute’s chief scientific officer. view article. trish to collaborate with polaris program on human health research in space during historic missionfeb. 14   trish will collaborate with the polaris program by conducting human health space research during the polaris dawn mission targeted to launch late 2022. read the release. trish: funding for companies to solve health challenges for lunar missionsjan. 20   the trish 2022 industry solicitation calls for medical monitoring and real time guidance proposals that could aid astronauts during lunar missions. read the release. future human spaceflight gets boost from inspiration4 researchdec. 10   trish researchers met with the inspiration4 crew to offer insights on research and data collected during the inspiration4 mission. read the release. trish seeks proposals to counteract spaceflight body wear and tear in brash 2201 solicitationdec. 1   trish announced the institute is seeking scientific proposals for disruptive technologies, therapies and/or approaches to protecting astronaut health through enhancing pre existing internal cellular repair functions in its brash 2201 solicitation. read the release. trish announces international research collaboration during space adventures' mz mission nov. 29   the trish sponsored human health and performance research will be part of space adventures yusaku maezawa's mission to the international space station (iss), launching dec. 8 from the baikonur cosmodrome in kazakhstan. read the release. trish demonstrates performance of portable handheld ultrasound in spacesept. 29   trish celebrates the success of the butterfly iq, an innovative medical imaging technology demonstration, aboard the international space station (iss). read the release. trish announces postdoc 2201 solicitationsept. 22   trish is seeking exceptional proposals from postdoctoral fellows ready to help solve the challenges of space exploration. the trish postdoctoral fellowship program supports early career scientists pursuing innovative, breakthrough research with the potential to reduce spaceflight associated health risks and improve astronaut performance. read the release. trish launches first commercial spaceflight medical research programsept. 7   trish launches expand, the first of its kind research platform to study human health and performance in private spaceflight participants. as part of the expand program, trish will work with commercial spaceflight providers and their passengers to collect inflight health data from multiple space flights and house it in a centralized research database. trish awards nearly $4m in awards in response to brash 2101 solicitationaug. 31   trish announced the selection of four creative proposals with never before tried ways to reduce potential damage to humans from the space environment through manipulation of metabolism and the normal state of being at the cellular or whole organism level. read the press release. trish research to launch into space aboard historic inspiration4 missionaug. 30   trish, in partnership with inspiration4, spacex and weill cornell medicine, announces human health research set to launch on the inspiration4 mission. the research projects will monitor the health of the crew and provide data to further human exploration of space. read the press release. trish awards four postdoctoral fellowships july 15   trish announced selection of four early career scientists to receive its postdoctoral fellowship award. read the press release. the butterfly iq catches a ride on the spacex dragon to spacejune 3   the 22nd spacex dragon cargo resupply payload included a trish supported technology: butterfly iq, the world's first handheld, single probe whole body ultrasound system using semiconductor technology. read the press release. trish adds astronauts, scientists to scientific advisory boardmarch 17   trish recently announced the appointment of seven outstanding thought leaders, including two astronauts, who joined the scientific advisory board. nasa grants renewal and funding for deep space health protectionsfeb. 26   after a favorable program review in december 2020, nasa has exercised its option to renew trish until 2028 receiving up to $134.6 million in additional funding to continue advancing space health research and technologies. read the news on space daily. trish receives renewal from nasafeb. 12   trish, was granted renewal from nasa this week, which will allow the organization to continue to conduct biomedical research geared at protecting astronauts in deep space through 2028. read innovationmap's article. trish releases brash 2101 solicitationoct. 23   trish's brash solicitation, released today, seeks novel research and multi disciplinary approaches to reduce health risks for mars explorers through manipulation of human metabolism and homeostasis at the cellular or whole organism level. step 1 proposals are due dec. 21, 2020 by 5 p.m. est. three innovative companies selected to guard the mind of mars explorerssept. 23   trish awarded z3vr, ejenta and holobiome grants to advance their innovative behavioral health technologies to address the needs of future long duration space missions. read the announcement. trish awards grants to mitigate the effects of space radiationsept. 18   trish has selected five research teams to advance the study of space radiation using human tissue/organ models. read the press release. trish awards postdoctoral fellowshipsjuly 1   trish announced five postdoctoral fellows selected to advance research in space translatable life science. read the press release. space health assists in covid 19april 20   the covid 19 pandemic is a huge challenge for health professionals everywhere. trish funded advances for space health are proving to be useful during this crisis. trish seeks space radiation research proposalsjan. 8   the institute released a new funding initiative supporting research advances in the study of space radiation and is seeking countermeasures for deep space exploration. find the solicitation here. read the news release here. trish seeks new postdoctoral fellowsoct. 28   trish announced it is soliciting proposals from postdoctoral researchers ready to help solve the health challenges of human deep space exploration. read the press release.hacking for health equityoct. 21   trish is participating the second annual health equity hackathon in houston, using newly available data to help address innovations for underserved communities. read the news release. trish announces new postdoc fellowsjuly 25   trish awarded postdoctoral fellowships to six outstanding early career scientists working in space translatable life sciences. trish announces two sleep studies for astronaut behavioral healthjune 17  trish and philips announced the selection of two research studies leveraging philips technology to evaluate if sleep can be made more efficient to improve cognitive function and behavioral health. trish selects industry 1901 proposalsapril 1   trish partnered with the consortia for improving medicine with innovation and technology to grant $1.5 million in awards to nine companies as part of the industry 1901 solicitation. the news release can be found here. trish seeks new postdoctoral fellowsoct. 28   trish announced it is soliciting proposals from postdoctoral researchers ready to help solve the health challenges of human deep space exploration. read the press release. hacking for health equityoct. 21   trish is participating the second annual health equity hackathon in houston, using newly available data to help address innovations for underserved communities. read the news release. trish announces new postdoc fellowsjuly 25   trish awarded postdoctoral fellowships to six outstanding early career scientists working in space translatable life sciences. trish announces two sleep studies for astronaut behavioral healthjune 17  trish and philips announced the selection of two research studies leveraging philips technology to evaluate if sleep can be made more efficient to improve cognitive function and behavioral health. trish selects industry 1901 proposalsapril 1   trish partnered with the consortia for improving medicine with innovation and technology to grant $1.5 million in awards to nine companies as part of the industry 1901 solicitation. the news release can be found here. what the polaris dawn mission could reveal about human health in space / the polaris dawn astronauts have returned to earth   but the real work has just begun sept. 16   trish deputy director and chief engineer jimmy wu recently discussed with the verge how spacex’s polaris dawn mission is advancing critical research on human health in space. ‘puffy head bird leg syndrome’: what space travel does to the body sept. 15   the sydney morning herald featured trish acting chief scientific officer dr. rihana simone bokhari alongside astronauts chris hadfield, katherine bennel pegg, and emmanuel urquieta, discussing the immense physical toll of space travel and its lasting impact on astronauts. polaris dawn crew conducts space health research for houston institute sept. 13   trish deputy director and chief engineer jimmy wu spoke with the houston chronicle about the polaris dawn mission and trish’s critical role in advancing space health research. first private spacewalk a success! what the spacex mission means for science sept. 12   trish deputy director and chief engineer jimmy wu spoke with nature about the polaris dawn mission and trish’s critical role in advancing space health research. antarctic research supports healthy space for astronauts sept. 11   the australian antarctic division (aad), in partnership with trish, is developing health monitoring technologies and strategies to support astronauts during long duration missions to the moon and mars, while also improving healthcare practices for remote communities on earth. why space is the next frontier to accelerate medical research sept. 10   in her spacenews op ed, trish executive director dr. dorit donoviel highlights the historic polaris dawn mission which enabled crucial health research to improve astronaut safety and advance medical innovations for earth. nasa’s human research program (hrp) features trish on nasa websitesept. 9   nasa’s human research program (hrp) collaborates with trish, featuring the institute on the nasa.gov website, to address health risks faced by astronauts on deep space missions. how much radiation starliner astronauts may have been exposed to while waiting to come home sept. 5   in this article, abc news talks with trish acting chief scientific officer rihana bokhari about the radiation dosage the starliner astronauts will have received during their extended stay aboard the iss, and how this exposure could impact their long term health. the science of polaris dawn and water under the surface of mars aug. 27   ahead of the polaris dawn launch, npr’s space exploration podcast are we there yet? talked with trish deputy director and chief engineer jimmy wu about the unique opportunities this mission provides for research in space health and beyond. how butch and suni’s bodies might respond to spending a longer amount of time in spaceaug. 22   in this episode of the business station’s podcast top 5 at 5, hear from trish’s acting chief scientific officer rihana bokhari about how the body changes in space, and how starliner astronauts butch wilmore and suni williams are maintaining their health during their extended stay at the international space station. out of the lab and into orbit: new trish selected baylor space health researchjuly 22   in this blog, trish communications fellow sarah kimmerly breaks down baylor’s new funding opportunity for space health research, highlights past successful research projects and introduces the program’s recent selections. fit to fly? penn researchers find some temporary cognitive decline among civilians who travel into space june 13   what does “fit for flight” mean for civilian astronauts? whyy news dives into the health standards for private astronauts, and how trish’s research initiatives and expand database are helping to inform them. motion sickness in space? a few days in earth’s orbit doesn’t put health at serious risk, study findsjune 12   health data collected from the first all commercial astronaut spaceflight suggests that short missions aren’t risky for civilian crews, according to a new study from trish researchers, from the houston chronicle. meet one of baylor’s space medicine pioneers and rising starsmay 21   meet dr. mohammad hirzallah, faculty with baylor college of medicine's center for space medicine, who toggles between being a principal investigator and a co investigator on various projects (including trish) and providing neurocritical care for patients in this blog by trish communications fellow shivani persaud. competing visionsapril   what’s the safest way to travel through the dangers of deep space? dr. emmanuel urquieta discusses the risks radiation poses to long duration missions to mars in this aerospace america article. health in space with dr. dorit donovielmarch 19   how is space research “tackling the ultimate challenge in problem solving,” from physiological and psychological health considerations and impacts to health on earth? trish executive director dr. dorit donoviel explains in episode 2 of inter astra institute’s podcast, your business in space. what would happen to a dead body in space? feb. 17   trish chief engineer jimmy wu tells live science all the details of what would happen to a body in space in the dangerous environment space provides. q&a: solving astronauts’ health challenges in deep space could have payoffs on earthfeb. 16   stat asked and trish executive director dr. dorit donoviel answered. in this q&a session, explore the risks of deep space travel, the research aimed to address them, and the ways in which their findings can help humans on and off the planet. the ‘wild west’ of space research feb. 1   how will the new wave of commercial spaceflight affect the rigor and quality of scientific research in space? in this article, trish executive director dorit donoviel talks with aerospace america about the need for guidelines that ensure safe and ethical research in space health. space health advancement reaches beyond borders jan. 30   trish communications fellow esha raut spotlights three of baylor college of space medicine’s international partners in this blog about the importance of international collaboration in space health. new effort seeks to study health issues for private astronauts jan. 26   in this spacenews article discussing various studies on the health of private astronauts, trish chief scientific officer jennifer fogarty emphasizes the importance of understanding the impact space travel has on women’s health. countdown continues for spacex mission headed to the international space station jan. 17   ahead of axiom space’s third mission to the international space station, trish chief medical officer emmanuel urquieta sits down with npr to discuss the changes astronauts experience before, during and after their time in space. space travel taxes astronauts’ brains. but microbes on the menu could help in unexpected ways jan. 16   how do we level up astronaut food to better support humans on the long trip to mars? trish executive director dr. dorit donoviel co authors this piece fo the conversation on the challenges of getting to mars, the relationship between diet and mental health, and the importance of microbes in maintaining the well being of our astronauts. bcm’s dr. klotman weekly video message  week 194 dec. 8   in this week’s video message, bcm president dr. klotman highlights the partnership between trish and the australian antarctic division (aad). the coldest continent on earth: an analog for space health research? dec. 7   in this blog, trish communications fellow shivani persaud compares the frigid environment of antarctica to the extreme nature of space, illustrating how we might leverage this similarity to better prepare astronauts for the mental and physical tolls of spaceflight. houston australia team to use antarctica's climate for space research dec. 4   how can antarctica help our understanding of space? trish chief medical officer dr. emmanuel urquieta talks with the houston chronicle about how trish and the australian antarctic division (aad) will use the extreme conditions of the south pole to advance health research in preparation for our journey to the moon and mars. the bodily indignities of the space life nov. 12   new york times magazine talks to trish’s drs. dorit donoviel, jennifer fogarty, and trish investigator dr. gordana vunjak novakovic about the gravity of expanding our lives beyond earth and how the human body could fare. bcm’s dr. klotman weekly video message   week 187 oct. 20   this week’s video from bcm president dr. paul klotman highlights the trish co authored astro ethics publication. can humans reproduce in space? oct. 20   trish executive director dr. dorit donoviel offers a realistic take on reproduction in space in this article with mit technology review. launching into the ethical dimensions of health research in space oct. 19   trish communications fellow esha raut shares the determined guidelines of ethical human health research in space in this blog, as a result of this trish co authored publication. back down to earth sept. 27   trish chief scientific officer dr. jennifer fogarty is featured on nbc nightly news, discussing the health and bodily impact of long durations in space. what 1 year in space does to the body as nasa astronaut frank rubio returns home sept. 27   trish’s chief scientific officer dr. jennifer fogarty speaks with abc news about the effects of space on the body considering astronaut frank rubio’s return in this article with abc news. astro ethics: grand ethical challenges for safeguarding human health in outer space sept. 8   who regulates health research when it extends beyond earth? trish senior communications associate madison hever highlights the challenges in the ethics of conducting human health research in space in this blog ahead of bcm’s bioethics grand rounds featuring trish’s dr. emmanuel urquieta, jimmy wu and trish investigator dr. eric bershad. now launching: space health sept. 5   in this blog, trish senior communications associate madison hever shares the initiatives the institute is focused on in advancing space health research and protecting astronauts in the future. center for space medicine, trish us spaceflight to advance healthcare on earth aug. 29   trish and csm’s senior communications associate madison hever discusses the importance of space health research in advance human space exploration in this blog. what happens if someone dies in space?july 31   what happens if someone dies in space? trish chief medical officer dr. emmanuel urquieta weighs the possible scenarios and logistics in the event of a death during a mission to space in this article for the conversation. the field of space medicine lifts offjuly 6   “there’s never been a better time to be in the field of space medicine than today,” said trish chief medical officer, dr. emmanuel urquieta in this article with aamc. crops grown without sunlight could help feed astronauts bound for marsjune 8   feeding mars bound astronauts: simple survival “is not the goal." trish chief scientific officer dr. jennifer fogarty explains to science magazine why today’s preserved food system “is completely inadequate for a mars mission.” researching in the commercial space industryjune 7   what can we learn about space health from the data collected on ax 2? trish chief medical officer dr. emmanuel urquieta explains on the innovationmap’s houston innovators podcast. is space the next frontier of health research?june 1   conducting drug research in space pushes product development to new heights, without the limits of gravity   resulting in advances for patients on earth, shares trish executive director dr. dorit donoviel at the 2023 aspen ideas festival. ucf college of medicine joins partnership to study health impacts of space travelmay 30   the university of central florida college of medicine announces its collaboration with trish to collect data and biospecimens from commercial spaceflight participants to better understand how space flight impacts health. ax 2 mission to conduct studies to mitigate negative effects of human spaceflightmay 24   ax 2 is a unique opportunity for trish researchers to collect more data on key human health metrics like cognition, vision, sleep, etc. learn about how the expand database is building our knowledge, thanks to private spaceflight partners in this axiom space blog. houston space research nonprofit announces new international agreementmay 8   innovationmap shares more on trish’s agreement with the korea national institute of health (knih) to collaborate on research and discovery relating to space health. q&a: why astronauts will need their own health data management platformapril 28   why will space explorers need their own health data management platform? trish deputy director and chief innovation officer james hury shares the answer with mobihealthnews. more private space missions mean more data on astronaut health april 25   trish chief scientific officer dr. jennifer fogarty and chief medical officer dr. emmanuel urquieta are featured on npr's wmfe are we there yet? podcast on leveraging the surge in private space missions to collect critical data on how space travel affects the human body. the final frontier of human sexuality may be in space feb. 14   trish chief medical officer dr. emmanuel urquieta spoke to inverse about the role of isolation and confinement in space and how the distance can impact the feeling of connectedness to family and friends on earth. the many, many reasons space travel is bad for the human bodyjan. 12   leaving earth upends almost every system inside the body. trish chief medical officer dr. emmanuel urquieta shares the demands space makes of the human body with the washington post, and the advances that need to be made for a successful future in space travel. good ethics to good science in commercial spaceflight researchjan. 6   trish communications and education officer rachael dempsey shares the aims of trish and baylor college of medicine in addressing the need for social responsibility in human health research in space. she highlights how the institute is closing the gap in this blog. spaceflight companies promised to do science   so, how's it going?dec. 20   research has historically taken a back seat in the space industry's initial jaunts into the cosmos, but trish executive director dr. dorit donoviel tells wired it's starting to pick up. trish postdoctoral fellowship is advancing space health research and careers nov. 10   trish postdoctoral fellow, dr. evan buettmann, shares his experience as a trish postdoc and gives advice to potential proposers in this blog. what healthcare insights can we gain from space exploration? nov. 7   trish deputy director and chief innovation officer james hury spoke with medcity news trish's work: adapting known tech for space applications and using space based insights to improve healthcare at home. the future of medicine in space: drug development, manufacturing, and beyond phantom oct. 6   what will the future of medicine in space look like? clinical trials arena spoke with trish chief medical officer dr. emmanuel urquieta about the risks to human health in space. phantom mannequins will help us understand how cosmic radiation affects female bodies sex in space will look like nothing we've ever seen beforesept. 22   the daily beast consulted trish chief scientific officer dr. jennifer fogarty on the implications and risks associated with conception in space. phantom mannequins will help us understand how cosmic radiation affects female bodiesaug. 19   popular science spoke to trish chief scientific officer dr. jennifer fogarty about the challenges and solutions for keeping humans, specifically females, healthy during artemis missions to the moon and future deep space missions. trish connects research for hydrocephalus to space healthjuly 22   trish investigator dr. michael williams, nasa astronaut dr. michael barratt, polaris dawn's kidd poteet, and trish leadership spoke at a panel during the hydrocephalus association annual conference. kxan shared the importance of space research to help find a solution to hydrocephalus on earth. space innovations lead to a healthier lifeapril 12   trish executive director dr. dorit donoviel’s tedx talk at baylor college of medicine focuses on how space health research can impact lives here on earth and the terrestrial applications of trish research. 4 astronauts will help scientists learn how space travel affects the human bodyapril 8   trish chief scientific officer dr. jennifer fogarty’s discussion with npr affiliate wmfe was featured on morning edition. trish research on the ax 1 missionapril 8   during the ax 1 launch live stream, trish chief medical officer dr. emmanuel urquieta explains each of the research projects that are collecting biomedical data on the ax 1 crew members. spacex private ax 1 mission’s science includes self assembling robots and light powered air filtersapril 4   space.com highlights research part of the ax 1 mission, including trish biomedical data collection. a new era of space science takes flight thanks to private civilian missionsmarch 29   as axiom space’s ax 1 mission prepares for launch, trish chief scientific officer dr. jennifer fogarty shares the benefits of increased access to space and what it could mean for space health research on wmfe’s are we there yet podcast. establishment of an open biomedical database for commercial spaceflightmarch 22   trish’s dr. dorit donoviel, james hury, dr. emmanuel urquieta, and jimmy wu draft a letter in nature medicine that highlights the work trish is doing in creating the first ever biomedical database for commercial spaceflight. astronaut blood samples reveal health risks posed by space flightmarch 10   trish funded investigator dr. david goukassian’s work is helping us access information on the health effects of spaceflight, including more data points that could help us build a clearer picture. trish chief scientific officer dr. jennifer fogarty offers context on a recently published paper in forbes. vcu researcher receives nasa funding to study bone, muscle loss in spaceflightfeb. 24   trish funded postdoctoral fellow dr. michael friedman was awarded nasa grant funding to research the effect of genetic factors on bone and muscle loss during low gravity spaceflight. read the story in commonwealth times. just a few months in space may permanently rewire your brainfeb. 22   what happens to your brain in space? trish chief scientific officer dr. jennifer fogarty says we can learn a lot about the body by the changes that happen in space. read the daily beast story. mars mission could bring health benefits on earthfeb. 9   trish chief medical officer, dr. emmanuel urquieta, talked to nature medicine about the benefits of space health research on future mars missions and the applications it can have on earth. it’s time to take reproduction in space seriouslyjan. 29   axios spoke to trish lead scientist dr. gary strangman for a space health perspective on whether humans can safely reproduce in space. study: astronauts are losing 3 million red blood cells every second in spacejan. 20   popular science tapped trish executive director dr. dorit donoviel for comment on a study suggesting astronauts may experience space anemia longer than previously thought. read the article. scientists want to see if humans can hibernate like squirrels while traveling in deep spaceoct. 21   the houston chronicle takes a deep dive into the selected projects from trish's brash 2101 solicitation, which will be studying the reduction of potential damage to humans from the space environment through manipulation of metabolism.disabled astronauts blaze new space trailsoct. 20   trish senior biomedical engineer jimmy wu shares the importance of keeping humans healthy in space in an article by scientific american.william shatner is now the oldest person to ever go to space: 'the most profound experience'oct. 13   after blue origin's successful trip to space that carried the oldest person to space, trish executive director dr. dorit donoviel explains to cnn the risks associated with spaceflight and whether age is a determining factor.william shatner is 90. is space travel even safe for him?oct. 4   as more space flight travelers explore beyond earth, trish's interim chief scientist and chief medical officer dr. emmanuel urquieta weighs in on whether age can have impact on the health of commercial space participants. read the daily beast article.space bound billionaires can help make the world a healthier place through researchsept. 24   after the excitement over the novelty of civilian trips to space, many wondered: "why don't billionaires spend their money to help people with problems we already have on earth, rather than spending it on exclusive jaunts to space?" trish scientific advisory board members co authored an opinion piece in stat news to offer a solution to the problem: research. houston innovator talks space health and the future of the commercial sectorsept. 22   as commercial space exploration continues and more people make it into space, new opportunities for space health research are being made available. trish deputy director and chief innovation officer james hury was featured on innovationmap’s houston innovators podcast about where human health research fits in the future of the commercial space industry.should the inspiration4 crew receive astronaut wings?sept. 18   after the faa changed the rules determining who gets astronaut wings earlier this year, npr asked trish’s thoughts on whether the inspiration4 crew, which conducted trish research while in orbit, should receive astronaut wings.baylor college of medicine’s trish working research initiative tied to inspiration4sept. 17   featured in the houston business journal, trish executive director dr. dorit donoviel and senior biomedical engineer jimmy wu share the importance of human health research aboard commercial space missions, like inspiration4.translational research institute for space health turns inspiration4 crew into health researcherssept. 17   spaceref shares how trish research is filling up the inspiration4 crew’s schedule while in orbit around the earth.who gets sick in space?sept. 16   as a more of humanity is venturing into space, beyond earth, the new york times speaks with trish executive director dr. dorit donoviel about how human health research can help the future of commercial spaceflight.space health to be explored during all civilian inspiration4 missionsept. 16   trish was featured in baylor college of medicine’s blog discussing the institute’s involvement and research with the inspiration4 mission.houston coordinated research for inspiration4 launchsept. 15   trish executive director dorit donoviel, ph.d. and trish principal investigator ashot sargsyan spoke with the houston chronicle to discuss the importance of the research that launched into space and the impact it can have on the future of space health research.historic launch carries human health research into spacesept. 15   univion’s despierta américa spoke with trish interim chief scientist and chief medical officer dr. emmanuel urquieta about the inspiration4, the role trish has in the mission. en español.inspiration4 crew to conduct experiments in orbit on behalf of houston researcherssept. 15   trish executive director dorit donoviel, ph.d. and trish principal investigator ashot sargsyan were featured on khou’s inspiration4 mission coverage in space city.trish facilitates science on spacex inspiration4 missionsept.15   trish interim chief scientist and chief medical officer dr. emmanuel urquieta and senior biomedical engineer jimmy wu explain the trish expand program and the research during the inspiration4 mission. watch the kprc2 story.houston based research institute launches experiments with first all civilian orbital crewsept. 15   houston matters talks inspiration4 experiments, human health research to mitigate challenges for future missions, and the difference of working with civilians versus professional astronauts with trish’s interim chief scientist and chief medical officer ahead of mission’s launch.all civilian inspiration4 launch to offer new science opportunitiessept. 14   trish interim chief scientist and chief medical officer dr. emmanuel urquieta and senior biomedical engineer jimmy wu demonstrate a couple of experiments that the inspiration crew participated in while in orbit. read the spectrum news13 article.spacex inspiration4 arrives in florida, will complete experiments during missionsept. 9   trish senior biomedical engineer jimmy wu explains how the trish inspiration4 projects can help protect humans from the harsh environment of space. watch the fox 35 orlando story.spacex inspiration4 mission will use apple watch and ipad for health research study in spacesept. 3   space explored speaks with trish senior biomedical engineer jimmy wu about how the data collected from the inspiration4 crew will contribute to our understanding of how the human body reacts to stress associated with spaceflight.trish presents award to student nurse at annual aerospace medicine meetingsept. 1   trish presented an award to a student nurse at the aerospace medical association (asma) annual meeting. the award facilitates scientific education in this unique nursing field and covers the costs for attendance at the 2022 asma conference.civilian space science   trish research headed to space on inspiration4 missionaug. 31   trish interim chief scientist and chief medical officer dr. emmanuel urquieta joined npr affiliate wmfe for its space podcast, are we there yet?, highlighting the research projects headed to space on the inspiration4 mission.inspiration4 expands health research on spaceflightaug. 31   mobihealthnews featured trish interim chief scientist and chief medical officer dr. emmanuel urquieta in an article discussing the trish research on the inspiration4 mission and the repository where the data will be stored for future research of the impact of spaceflight on the human body.spaceflight concerns for the human body as commercial companies start sending more humans to spacejuly 9   as more commercial spaceflight companies begin sending humans to space, trish chief medical officer dr. emmanuel urquieta spoke with the telegraph about the many impacts spaceflight can have on the human body.health concerns during the mission to mars and deep space traveljune 27   emmanuel urquieta, m.d. spoke with kprc 2 houston newsmakers about the challenges scientists and researchers face in gearing up for missions to mars and what trish is aiming to develop to protect the health of the crew. what happens when you have a heart attack on the way to mars?may 4   emmanuel urquieta, m.d. spoke to wired about what would happen if crew falls sick on a mission to mars, and how trish is innovating to prepare for the worst case scenarios.health and safety in space, the final frontier?april 15   dorit donoviel, ph.d. spoke to canadian occupational safety magazine about the everyday things about life in space that forces innovation.'why we go' space exploration series launchesapril 7   trish and asu's interplanetary initiative kick off a four part virtual series diving into the philosophy and passions behind the desire to travel into deep space. read the news from asu.startup adapts ai used in space to advance healthcare on earthapril 6   forbes profiled ejenta, a trish funded startup that uses ai to advance healthcare for space and earth.nasa grants renewal and funding for deep space health protectionsfeb. 26   after a favorable program review in december 2020, nasa has exercised its option to renew trish until 2028 receiving up to $134.6 million in additional funding to continue advancing space health research and technologies. read the news on space daily.four female houston innovators to knowfeb. 22   trish's director, dorit donoviel, ph.d., was included in innovationmap's roundup of houston innovators to know.trish receives renewal from nasafeb. 12   trish, was granted renewal from nasa this week, which will allow the organization to continue to conduct biomedical research geared at protecting astronauts in deep space through 2028. read innovationmap's article.opinion: the future of spaceflight is femalejan. 23   what do all 12 of the elite apollo astronauts who have walked on the moon have in common? they're all male. trish director dr. dorit donoviel shares why the future of spaceflight is female in this houston chronicle op ed.to boldly go where no pharma has gone beforejan. 14   as featured in neo.life, astropharmacies could grow drugs on demand for future space travelers.microbiome for marsjan. 4   in case you missed trish's "microbiome for mars" workshop, this microbiome journal article summarizes current microbiome research, future endeavors and how this growing field could broadly impact human health and space exploration. scientists want to see if humans can hibernate like squirrels while traveling in deep spaceoct. 21   the houston chronicle takes a deep dive into the selected projects from trish's brash 2101 solicitation, which will be studying the reduction of potential damage to humans from the space environment through manipulation of metabolism. disabled astronauts blaze new space trailsoct. 20   trish senior biomedical engineer jimmy wu shares the importance of keeping humans healthy in space in an article by scientific american. william shatner is now the oldest person to ever go to space: 'the most profound experience'oct. 13   after blue origin's successful trip to space that carried the oldest person to space, trish executive director dr. dorit donoviel explains to cnn the risks associated with spaceflight and whether age is a determining factor. william shatner is 90. is space travel even safe for him?oct. 4   as more space flight travelers explore beyond earth, trish's interim chief scientist and chief medical officer dr. emmanuel urquieta weighs in on whether age can have impact on the health of commercial space participants. read the daily beast article. space bound billionaires can help make the world a healthier place through researchsept. 24   after the excitement over the novelty of civilian trips to space, many wondered: "why don't billionaires spend their money to help people with problems we already have on earth, rather than spending it on exclusive jaunts to space?" trish scientific advisory board members co authored an opinion piece in stat news to offer a solution to the problem: research. houston innovator talks space health and the future of the commercial sectorsept. 22   as commercial space exploration continues and more people make it into space, new opportunities for space health research are being made available. trish deputy director and chief innovation officer james hury was featured on innovationmap’s houston innovators podcast about where human health research fits in the future of the commercial space industry. should the inspiration4 crew receive astronaut wings?sept. 18   after the faa changed the rules determining who gets astronaut wings earlier this year, npr asked trish’s thoughts on whether the inspiration4 crew, which conducted trish research while in orbit, should receive astronaut wings. baylor college of medicine’s trish working research initiative tied to inspiration4sept. 17   featured in the houston business journal, trish executive director dr. dorit donoviel and senior biomedical engineer jimmy wu share the importance of human health research aboard commercial space missions, like inspiration4. translational research institute for space health turns inspiration4 crew into health researcherssept. 17   spaceref shares how trish research is filling up the inspiration4 crew’s schedule while in orbit around the earth. who gets sick in space?sept. 16   as a more of humanity is venturing into space, beyond earth, the new york times speaks with trish executive director dr. dorit donoviel about how human health research can help the future of commercial spaceflight. space health to be explored during all civilian inspiration4 missionsept. 16   trish was featured in baylor college of medicine’s blog discussing the institute’s involvement and research with the inspiration4 mission. houston coordinated research for inspiration4 launchsept. 15   trish executive director dorit donoviel, ph.d. and trish principal investigator ashot sargsyan spoke with the houston chronicle to discuss the importance of the research that launched into space and the impact it can have on the future of space health research. historic launch carries human health research into spacesept. 15   univion’s despierta américa spoke with trish interim chief scientist and chief medical officer dr. emmanuel urquieta about the inspiration4, the role trish has in the mission. en español. inspiration4 crew to conduct experiments in orbit on behalf of houston researcherssept. 15   trish executive director dorit donoviel, ph.d. and trish principal investigator ashot sargsyan were featured on khou’s inspiration4 mission coverage in space city. trish facilitates science on spacex inspiration4 missionsept.15   trish interim chief scientist and chief medical officer dr. emmanuel urquieta and senior biomedical engineer jimmy wu explain the trish expand program and the research during the inspiration4 mission. watch the kprc2 story. houston based research institute launches experiments with first all civilian orbital crewsept. 15   houston matters talks inspiration4 experiments, human health research to mitigate challenges for future missions, and the difference of working with civilians versus professional astronauts with trish’s interim chief scientist and chief medical officer ahead of mission’s launch. all civilian inspiration4 launch to offer new science opportunitiessept. 14   trish interim chief scientist and chief medical officer dr. emmanuel urquieta and senior biomedical engineer jimmy wu demonstrate a couple of experiments that the inspiration crew participated in while in orbit. read the spectrum news13 article. spacex inspiration4 arrives in florida, will complete experiments during missionsept. 9   trish senior biomedical engineer jimmy wu explains how the trish inspiration4 projects can help protect humans from the harsh environment of space. watch the fox 35 orlando story. spacex inspiration4 mission will use apple watch and ipad for health research study in spacesept. 3   space explored speaks with trish senior biomedical engineer jimmy wu about how the data collected from the inspiration4 crew will contribute to our understanding of how the human body reacts to stress associated with spaceflight. trish presents award to student nurse at annual aerospace medicine meetingsept. 1   trish presented an award to a student nurse at the aerospace medical association (asma) annual meeting. the award facilitates scientific education in this unique nursing field and covers the costs for attendance at the 2022 asma conference. civilian space science   trish research headed to space on inspiration4 missionaug. 31   trish interim chief scientist and chief medical officer dr. emmanuel urquieta joined npr affiliate wmfe for its space podcast, are we there yet?, highlighting the research projects headed to space on the inspiration4 mission. inspiration4 expands health research on spaceflightaug. 31   mobihealthnews featured trish interim chief scientist and chief medical officer dr. emmanuel urquieta in an article discussing the trish research on the inspiration4 mission and the repository where the data will be stored for future research of the impact of spaceflight on the human body. spaceflight concerns for the human body as commercial companies start sending more humans to spacejuly 9   as more commercial spaceflight companies begin sending humans to space, trish chief medical officer dr. emmanuel urquieta spoke with the telegraph about the many impacts spaceflight can have on the human body.health concerns during the mission to mars and deep space traveljune 27   emmanuel urquieta, m.d. spoke with kprc 2 houston newsmakers about the challenges scientists and researchers face in gearing up for missions to mars and what trish is aiming to develop to protect the health of the crew. what happens when you have a heart attack on the way to mars?may 4   emmanuel urquieta, m.d. spoke to wired about what would happen if crew falls sick on a mission to mars, and how trish is innovating to prepare for the worst case scenarios. health and safety in space, the final frontier?april 15   dorit donoviel, ph.d. spoke to canadian occupational safety magazine about the everyday things about life in space that forces innovation. 'why we go' space exploration series launchesapril 7   trish and asu's interplanetary initiative kick off a four part virtual series diving into the philosophy and passions behind the desire to travel into deep space. read the news from asu. startup adapts ai used in space to advance healthcare on earthapril 6   forbes profiled ejenta, a trish funded startup that uses ai to advance healthcare for space and earth. nasa grants renewal and funding for deep space health protectionsfeb. 26   after a favorable program review in december 2020, nasa has exercised its option to renew trish until 2028 receiving up to $134.6 million in additional funding to continue advancing space health research and technologies. read the news on space daily. four female houston innovators to knowfeb. 22   trish's director, dorit donoviel, ph.d., was included in innovationmap's roundup of houston innovators to know. trish receives renewal from nasafeb. 12   trish, was granted renewal from nasa this week, which will allow the organization to continue to conduct biomedical research geared at protecting astronauts in deep space through 2028. read innovationmap's article. opinion: the future of spaceflight is femalejan. 23   what do all 12 of the elite apollo astronauts who have walked on the moon have in common? they're all male. trish director dr. dorit donoviel shares why the future of spaceflight is female in this houston chronicle op ed. to boldly go where no pharma has gone beforejan. 14   as featured in neo.life, astropharmacies could grow drugs on demand for future space travelers. microbiome for marsjan. 4   in case you missed trish's "microbiome for mars" workshop, this microbiome journal article summarizes current microbiome research, future endeavors and how this growing field could broadly impact human health and space exploration. astronauts discuss ways to cope with anxiety, lonelinessoct. 13   americans are working to cope with the loneliness that accompanies the fight against the spread of the coronavirus. this usa today article turned to experts at figuring out how to endure anxiety, loneliness and social separation safely and sanely   astronauts. staying sane on the mission to marsoct. 26   as featured on medcity news, dr. dorit donoviel, discusses what it will take to get humans to mars, safe and sane. trish supports postdocs with 'go for launch' programnov. 10   trish launched the 'go for launch' program to provide funding opportunities to third year fellows while they job search during the pandemic. read trish's letter to the editor on nature. spaceflight does some weird things to astronauts' bodiesnov. 25   dr. jeffrey p. sutton, a member of trish's board of directors, weighs in on the good, the bad and the inexplicable biological changes that occur in all astronauts during spaceflight in this mit technology review article. space is dangerous, especially when you can’t call home for helpoct. 22   trish’s deputy chief scientist dr. emmanuel urquieta spoke to science news for students about the dangerous health concerns that face those brave enough to undertake the first mission to mars. “far from home” storyteller event features astronauts, trish staffoct. 22   trish director dr. dorit donoviel and deputy chief scientist dr. emmanuel urquieta participated in usa today’s storytellers project event alongside astronauts nicole stott, cady coleman and dr. david hilmers. the virtual event shared stories from space explorers and scientists preparing for the mission to mars, and what they learned about loneliness and isolation from space. donoviel did a q&a about how to apply the lessons from space to coping during the pandemic. watch the show here. houston virtual reality company z3vr says trish funding “means the world”oct. 14   z3vr spoke to innovation map about designing behavioral health solutions for astronauts. the company recently received a trish industry grant. usa today talks with trish director on top five tips to combat anxiety, lonelinessoct. 13   trish director dr. dorit donoviel spoke with usa today about top tips for fighting anxiety and loneliness while socially distancing during the covid 19 pandemic. trish deputy chief scientist discusses space medicine on medical podcastoct. 9   dr. emmanuel urquieta talked about the unique challenges of space medicine on the corconsult healthcare podcast. trish chief scientist gives lecture on deep space health risksoct. 8   dr. kristin fabre gave a lecture on the risks and hazards of deep space exploration as part of carnegie mellon’s challenging boundaries fall seminar series. trish director joins “above and beyond for women” paneloct. 8   dr. dorit donoviel was featured as one of three speakers at the ellevate houston above and beyond for women panel. she joined nasa flight surgeon dr. moriah thompson and nasa chief scientist dr. julie robinson. researchers studying faster diagnosis, treatment of brain injuries, with trish fundingoct. 1   uthealth researchers, funded by trish, are investigating using artificial intelligence and retinal cameras to diagnose strokes without the need for a mri or ct scan. their research was recently featured on uthealth news. new rapid detection sensor for covid 19 comes from trish fundingoct. 1   caltech researchers, with trish funding, have developed a new type of covid 19 test that could enable at home diagnosis in less than 10 minutes. the researchers hope to start testing hospitalized covid 19 patients soon. what nasa can teach us about social isolationsept. 23   how do we combat loneliness and social isolation when physical distancing is critical? the "creating a new healthcare" podcast featured trish's dr. gary strangman and how findings from space missions drive solutions for all. wisdom from the women leading the space industryaug. 16   trish director dr. dorit donoviel was interviewed for authority magazine’s series “women leading the space industry.” dr. donoviel candidly gives her perspectives about the most exciting aspects the space industry, the changes and challenges needed regarding women in stem, five leadership lessons, and more. incredible, radiation fighting duckweedjuly 14   trish pi barbara demmig adams from the university of colorado boulder shared her work to optimize duckweed for use in spaceflight, where space, resources and fresh food are limited. read the research brief in the conversation. coronavirus hasn’t hit space   yetmay 27   dr. dorit donoviel spoke to politico about covid 19 and implications for health in space. houston: we are on a podcastmay 8   trish director dr. dorit donoviel and trish chief scientist dr. kristin fabre talked innovations for mars with nasa’s houston we have a podcast. detecting stress through your sweatfeb. 26   trish funded researcher dr. wei gao is taking his research on sweat sensors used to detect stress and developing it to monitor stress and anxiety in space explorers. from caltech news. video games reshape how we think of life after earthfeb. 25   onezero featured trish partner level ex and how it’s using video game technology to help assist astronauts properly diagnosis conditions in space. thought leadership in space healthjan. 26   authority magazine interviewed trish director dr. dorit donoviel on being a thought leader in the space medicine industry. the future of making drugs in spacejan. 23   trish deputy chief scientist dr. emmanuel urquieta spoke with pharma technology focus on how trish funded research will allow drugs to be manufactured in space. innovating in space cityjan. 15   the houston innovators podcast hosted trish director dr. dorit donoviel for a discussion on how the institute takes risk to advance space medicine. video game tech helps doctors workjan. 9   the washington post spoke to trish funded partner level ex on how its video game simulation can help keep astronauts healthy on long space journeys. trish’s holistic approach to astronaut healthnov. 22   trish senior innovation scientist dr. kristin fabre spoke with himss tv about how the institute helps make advances in space health. designing health wearables for astronautsnov. 20   trish partnered with medical device company empatica to develop a wearable monitor to track astronaut health. the company was previously known for creating the first smart watch used to detect seizures. read more. space health innovation conference launches in san francisconov. 5   trish’s space health innovation conference has mobihealth news thinking about test driving health technology for the longest space journey yet, and spoke to trish’s senior innovation scientist kristin fabre about what’s coming next. mission to mars: the healthcare challenges facing nasanov. 4   at shic, nasa scientists, astronauts and partners discussed the future of space health. read the interview with trish leadership on nasa’s healthcare challenges from mobihealth news. medical gaming for astronaut simulationoct. 31   forbes explores the future of gaming for space: medical training simulations by trish funded gaming company, level ex. exploring the new health frontiers in spaceoct. 24   luminary labs spoke with trish scientists dr. emmanuel urquieta about the future of health and exploring its new frontiers in space. read the interview from luminary labs. future starship updates could use more details on human health and survivaloct. 4   the verge spoke to trish director dr. dorit donoviel about the questions that still remain for protecting human health in space   even aboard the spacex starship rocket. how does space travel impact health?sept. 30   texas a&m today and vital record took a look at a trish funded study that will investigate the possibility of developing first ever international medical database for retired astronauts. from jedis to astronautsaug. 30   cnbc covered the jump from jedis to astronauts and how trish is working with game developer to improve astronaut training. testing wearables for sleep improvements in spacejuly 27   can a sleep device give deep space explorers a good night’s rest? trish is funding investigators from the wisconsin institute for sleep and consciousness to test it out. health discoveries enabled by space explorationjuly 19   dr. dorit donoviel channels the spirit of the apollo program for the hill  and lists some of the medical technologies enabled by the space program. who will be the first woman to walk on the moon?july 18   neil armstrong was the first man to walk on the moon. who will be the first woman? trish director dr. dorit donoviel spoke to the los angeles times about the future of women in space. the moon is a hazardous place to livejuly 8   the new york times spoke to dr. dorit donoviel about the harsh realities of the lunar surface. healthtech innovator backed by trish works on space related eye conditions june 21   dallas innovates took a look at the work of trish funded investigator dr. tasneem sharma and her patent pending device to study a condition affecting astronauts returning from outer space. trish announces two sleep studies for astronaut behavioral healthjune 17  trish and philips announced the selection of two research studies leveraging philips technology to evaluate if sleep can be made more efficient to improve cognitive function and behavioral health. rtsleepworld, homecare magazine, hme news and yahoo finance shared the news. space tomatoes funded by trish could feed future astronautsmay 3  researchers at the university of california, riverside are developing tomatoes with minimal biomass but a normal amount of fruit, thanks to a grant from trish. greenhouse grower highlighted the research effort. may 3   the new food economy highlights the work of trish investigators using gene editing to produce tiny tomatoes for space exploration. april 25   uc riverside news covers the trish funded tiny tomato plants developed at the university of california, riverside, could one day feed astronauts on the international space station. tiny ‘tissue chips’ are a big deal for space health researchmay 3   the national institutes of health sent 3d microphysiological systems, or tissue chips, to the international space station lab. for trish, the research model opens up new possibilities to understand what happens to human organs during long space flights. a piece by baylor college of medicine about this innovative new technique can be found here. study of twin astronauts features multiple trish funded projectsapril 11  astronaut scott kelly’s dna had multiple changes after a year in space, according to recently published study partly funded by trish. scott and his twin brother mark’s dna were part of the groundbreaking twin study. trish funded researchers from cornell university helped develop dna sequencing techniques that could detect epigenetic changes in space. read more in the cornell chronicle. trish director speaks about scrapped all female spacewalkmarch 26   trish director dr. dorit donoviel was interviewed by canada’s ctv about the postponed all female spacewalk. red risk school highlights space health problems, solutionsmarch 18 22   trish’s red risk school showcased nasa’s top human health risks for deep space exploration. the expert led scientific webinar featured topics such as radiation, spaceflight associated neuro ocular syndrome or sans, and in flight medical capabilities. red risk school also covered trish’s current investigation portfolio and research funding priorities. a recorded version of the webinar is available here. space, like love, changes the human heartfeb. 14   on valentine’s day, the verge published a light hearted piece about how space flight affects the human heart. trish director dr. dorit donoviel was interviewed for the story. space2 workshop explores how confined environments affect healthfeb. 6 7   the massachusetts institute of technology and trish collaborated to present the space 2 workshop. the event focused on how the lack of space during spaceflight can affect the health of astronauts on board. the verge, psychology today and techrepublic each wrote pieces about the workshop. johnson space center highlights trish funded devicefeb. 4   johnson space center highlighted the butterfly iq, a small but highly capable ultrasound tool, in its latest news roundup. the butterfly iq was created by butterfly networks and helped into nasa operations by trish. follow us ©1998 2023 baylor college of medicine® | one baylor plaza, houston, texas 77030 | 713 798 4951have an edit or suggestion for this page?

an official website of the united states government official websites use .gov a .gov website belongs to an official government organization in the united states. secure .gov websites use https a lock ( lock locked padlock icon ) or https:// means you've safely connected to the .gov website. share sensitive information only on official, secure websites. primary site navigation logged in as: corresponding author. received 2023 may 2; accepted 2024 may 15; collection date 2024. open access this article is licensed under a creative commons attribution 4.0 international license, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the creative commons licence, and indicate if changes were made. the images or other third party material in this article are included in the article’s creative commons licence, unless indicated otherwise in a credit line to the material. if material is not included in the article’s creative commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. to view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. the spacex inspiration4 mission provided a unique opportunity to study the impact of spaceflight on the human body. biospecimen samples were collected from four crew members longitudinally before (launch: l 92, l 44, l 3 days), during (flight day: fd1, fd2, fd3), and after (return: r + 1, r + 45, r + 82, r + 194 days) spaceflight, spanning a total of 289 days across 2021 2022. the collection process included venous whole blood, capillary dried blood spot cards, saliva, urine, stool, body swabs, capsule swabs, spacex dragon capsule hepa filter, and skin biopsies. venous whole blood was further processed to obtain aliquots of serum, plasma, extracellular vesicles and particles, and peripheral blood mononuclear cells. in total, 2,911 sample aliquots were shipped to our central lab at weill cornell medicine for downstream assays and biobanking. this paper provides an overview of the extensive biospecimen collection and highlights their processing procedures and long term biobanking techniques, facilitating future molecular tests and evaluations.as such, this study details a robust framework for obtaining and preserving high quality human, microbial, and environmental samples for aerospace medicine in the space omics and medical atlas (soma) initiative, which can aid future human spaceflight and space biology experiments. subject terms: molecular biology, genetics, biomarkers here the authors provide the biospecimen collection methodology from the spacex inspiration4 mission, including venous blood, capillary blood, saliva, urine, stool, skin biopsy, body swab, and environmental swab samples. our human space exploration efforts are at a unique transition point in history, with more crewed launches and human presence in space than ever before1. we can attribute this to the commercial spaceflight sector entering an industrial renaissance, with multiple companies forming collaborative and competitive networks to send commercial astronauts into space. the recent advancements in human space exploration offer a significant chance to gather more biological research samples and enhance our comprehension of spaceflight’s effects on human health. this is vital, as our knowledge of the biological reactions to the unique environment of space, marked by microgravity and the space radiation, remains incomplete2. the impact of spaceflight on human health includes musculoskeletal deconditioning3, cardiovascular adaptations4, vision changes5, space motion sickness6, neurovestibular changes7, immune dysfunction8, and increased risk of rare cancers9, among other changes2. however, we are still at the initial stages of documenting biological responses to spaceflight exposure at the molecular and cellular resolution. prior work has characterized molecular changes that occur during spaceflight in astronauts. these include changes in cytokine profiles8,10,11, urinary albumin abundance12, and hemolysis13. furthermore, multiomic assays have provided genomic maps of structural changes in dna14 16, rna expression profiles11,17,18, sample wide protein measurements17,19,20, and metabolomic status17. additionally, international space station (iss) surfaces have been studied with longitudinal microbial profiles to track microbial pathogenicity and evolution to assess their potential influence on crew health21,22. to better improve our understanding of both human and microbial biology in space, it is critical that these analyses continue and expand as more spacecraft and stations are built and flown. combining and comparing work from prior missions in these new spacecraft and stations is especially important to overcome the small sample sizes and highlights a need for standardization between missions. in addition, recruiting large cohorts of astronauts is difficult, as the iss typically can only house up to six astronauts at a time. as of the time of writing, only 647 humans have been to space, starting with the launch of yuri gagarin in 1961. studies have spanned the vostok program, project mercury, the voskhod program, project gemini, project apollo, the soyuz program, the salyut space stations, mir, the space shuttle program, skylab, tiangong space station, and the iss. from the breadth of experiments that have been performed on the iss, only a minority have specifically been human research oriented23,24, and just a subset involve omics studies. the nasa twin study created the most in depth multi omic study of astronauts prior to inspiration4, but was limited to one astronaut and one ground control17. these factors have limited the statistical power of astronaut omic experiments and increased the difficulty of providing robust scientific conclusions. standardizing biospecimen collections across multiple missions will create larger sample sets needed to draw these conclusions. here, we establish the standard biospecimen sample collection and banking procedures for the space omics and medical atlas (soma). a key goal of soma is to standardize biospecimen collection and processing for spaceflight, to generate high quality multi omics data across spaceflight investigations, and to enable follow up experiments with viably frozen cells and biobanked samples. this paper provides sample collection methods built for standardized field collections across different crews and missions. we cover the decentralized sample collection process from the inspiration4 (i4) mission from the point of collection to the preservation of samples for downstream biochemical and omics processing at our centralized lab at weill cornell medicine (wcm). these protocols can produce synchronized datasets with enhanced statistical strength, amplifying our scientific findings from spaceflight studies. additionally, we showcase metrics related to sample collection outputs, references of past astronaut sample collections in scientific publications, and suggestions to refine sample collection for upcoming missions. in its inaugural use case, these samples were collected from the i4 astronaut cohort and are currently in use for several other missions (polaris dawn, axiom 2), which will enable continued utilization for future crewed space missions. we formulated and executed a sampling plan that spans a wide range of biospecimen samples: venous blood, capillary dried blood spots (dbss), saliva, urine, stool, skin swabs, skin biopsies, and environmental swabs (fig. 1a). the collection of various types of samples covered the scope of previous assays on astronaut samples (supplementary table 1), but also enabled newer omics technologies, such as spatially resolved, single molecule, and single cell assays. a list of biospecimen samples collected over the course of the study. b timepoints for each biospecimen sample collection. “l ” denotes the number of days prior to launch. “r + ” denotes the number of days after return to earth. “fd” denotes which day of the flight a sample was collected. c location of each collection timepoint. for the i4 mission, sample collection spanned three time points pre launch (l 92, l 44, l 3 days), three time points during flight (flight day 1 (fd1), fd2, fd3), and four time points post return (r + 1, r + 45, r + 82, r + 194 days). venous blood, urine, stool, and skin biopsies were collected during ground timepoints only, while capillary dbss, saliva, and skin swabs were collected both on the ground and during flight (fig. 1b). environmental swabs of the dragon capsule were collected pre flight in the crew training capsule and during flight in the spacecraft launched from cape canaveral (fig. 1b). samples were collected across a variety of locations based on the crew’s training and travel schedule. l 92 and l 44 were collected in hawthorne, ca at spacex headquarters, l 3 and r + 1 were collected at cape canaveral, fl at a facility near the launch site. fd1, fd2, and fd3 were collected inside the dragon capsule while in orbit. r + 45 was collected at the crew members’ individual locations (which spanned the us states ny, nj, tn, and wa), r + 82 was collected at weill cornell medicine, ny and r + 194 was collected at baylor college of medicine, tx (fig. 1c). all samples from ground timepoints were processed within 16 hours of collection. all samples from the flight were processed immediately after retrieval from the flight. samples were stored at −80 °c at each site immediately after processing and aliquoting (processing steps are outlined below). all samples were shipped via fedex using overnight shipping to weill cornell medicine for storage in the cornell aerospace medicine biobank (cambank) within 1 week of collection on dry ice in styrofoam boxes and spent <2 days in transit. no samples were shipped on a thursday or friday to avoid weekend shipping delays. all samples arrived at weill cornell medicine with dry ice still in the packaging and samples frozen. samples were immediately transferred to −80 °c for long term storage and biobanking. any exceptions to this process will be noted below. in total, we collected 2,911 sample aliquots, which were then processed in our central lab at weill cornell medicine for downstream assays (supplementary table 2). some samples were processed immediately at field laboratory facilities (supplementary data fig. 1). dna and rna yields are also reported below from collection kits (saliva and stool) after arrival at wcm. blood was collected using a combination of venipuncture tubes to collect venous blood and contact activated lancets to collect capillary blood from the fingertip. each crew member provided blood samples, collected into one bd paxgene blood rna tube (brna), four bd vacutainer k2 edta tubes, two bd vacutainer cell preparation tubes (cpts), one streck cell free dna tube (cfdna bct), one bd vacutainer serum separator tube (sst), and one dbs card per time point. tubes were transported from the collection site to the field laboratory at room temperature. from these tubes, whole blood, plasma, pbmcs, serum, and cell pellet samples were collected (supplementary table 3). sample yields are reported below. samples were aliquoted for long term storage and biobanking (supplementary table 4). brna tubes were collected in order to isolate total rna using the paxgene blood rna kit (fig. 2a). yield ranged from 3.04 to 14.04 µg/tube of total rna across all samples, and the rna integrity number (rin) ranged from 3.2 to 8.5 (mean: 6.95) (fig. 2b). rna was stored at −80 °c after extraction. the collection of total rna enables a variety of downstream rna profiling methods. it will allow comparative studies to prior rna sequencing performed on astronauts, particularly snorna & lncrna biomarkers analyzed from space shuttle era blood25,26, mrna & mirna measured during the nasa twin study17,18, and whole blood rna arrays from the iss27,28. additionally, rna yields are more than sufficient to perform direct rna sequencing using oxford nanopore technologies (ont) platforms, which require 500 ng of total rna per library (manufacturer’s protocol, ont kit sqk rna002). this enables the study of rna modification changes during spaceflight to create epitranscriptomic profiles for the first time in astronauts. a one 2.5 ml brna tube was collected per crew member at each ground timepoint. b brna tube total rna yields per sample (μg) and rins. c four k2 edta tubes were collected per member at each ground timepoint. one tube was used for a cbc, one tube was used to isolate evps, and two tubes were used for isolation of pbmcs. d plasma and evp yields from the “[2] evps” tube on fig. 2c. e pbmc yields per ml from the “[3] pbmcs” tubes on fig. 2c. four k2 edta tubes were drawn at each timepoint from each crew member (fig. 2c). one k2 edta tube was submitted to quest diagnostics to perform a complete blood count (cbc, quest test code: 6399). one tube was used to isolate extracellular vesicles and particles (evps) for proteomic quantification (fig. 3a). total evp quantities varied from 2.71 28.27 ug (fig. 2d). two k2 edta tubes were used to isolate pbmcs for single cell sequencing (10x chromium single cell multiome atac + gene expression and chromium single cell immune profiling workflows). after collection, a ficoll separation was performed to isolate pbmcs, which ranged from 340,000 975,000 cells per ml of blood (fig. 2e). one prior single cell gene expression experiment, nasa twin study, was performed on astronauts, which found immune cell population specific gene expression changes and a correlation with microrna signatures11,18. centrifuge (brown circles) and aliquoting (white and green boxes and circles) protocols for a k2 edta tubes designated for evp isolation b cpts c cfdna bcts ans.d d sst. additional pbmcs, plasma, and serum were collected from cpts (fig. 4a), cfdna bcts (fig. 4d), ssts (fig. 4c), as well as red blood cell pellets. cpts were spun and aliquoted according to the manufacturer’s instructions (fig. 3b). plasma volume per tube ranged from 3000 14,000 ul per tube (fig. 4d). because of technical issues in the sample processing procedure, three instances occurred where plasma retrieval from the cpt tubes was not possible. plasma can be used to validate or refute previous studies, including cytokine panel10,29, exosomal rna seq25,26, extracellular vesicle microrna30, and proteomic20,31 33 results. pbmcs were also collected, aliquoted into 6 cryovials per cpt, and stored in liquid nitrogen after slowly cooled in a mr. frosty to  80 °c. these can be used to follow up on previous studies on adaptive immunity, cell function, and immune dysregulation8,34 39. the remaining red blood cell pellet mixtures from below the gel plug in each cpt tube were stored at −20 °c. a a spun cpt yields plasma, pbmcs, and a red blood cell pellet. pbmc from each tube were divided into 6 cryovials and viably frozen. plasma was aliquoted and the pellet was frozen at −20c. b a spun cfdna bct yields plasma and a red blood cell pellet. plasma was purified with an additional spin (see fig. 4a) then aliquoted. the pellet was frozen at −20c. c a spun sst yields serum and a red blood cell pellet. serum was aliquoted and the pellet was frozen at −20c. d cpt plasma volumes per timepoint are reported. e cfdna (streck) bct plasma volumes per timepoint. f sst serum volumes per timepoint. an extra tube was drawn for c004 at r + 45, resulting in a higher serum yield. cfdna bct (streck) tubes were collected to isolate high quality cfdna from plasma. cfdna bcts were spun and aliquoted according to the manufacturer’s instructions (fig. 3c). the remaining cell pellet mixture was frozen at −20 °c. plasma volume per timepoint ranged from 1500 5000 ul (fig. 4e). 500 ul aliquots were frozen at  80 °c. cfdna extracted from these tubes can be analyzed for fragment length, mitochondrial or nuclear origin, and cell type or tissue of origin40 42. the sst was spun and aliquoted according to the manufacturer’s instructions (fig. 3d). serum volume ranged from 2000 8000 ul per timepoint (fig. 4f). similar to plasma, serum can be allocated for cytokine analysis and can also be used to perform comprehensive metabolic panels, including one we used at quest (cmp, quest test code: 10231) for metrics on alkaline phosphatase, calcium, glucose, potassium, and sodium, among other metabolic markers. the remaining cell pellet mixture from each sst tube was stored at −20 °c. in addition to venous blood, capillary blood was collected onto a dbs card using a contact activated lancet pressed against the fingertip (fig. 5a). capillary blood was collected onto a whatman 903 protein saver dbs card to preserve nucleic acids and proteins. each of the five spots on the dbs card hold 75 80ul of capillary blood, however, the amount of capillary blood collected across timepoints varied (fig. 5b, c) according to how much blood could be collected before the lancet puncture closed. a dbs cards were collected preflight, during flight, and postflight. there were five spots for blood collection per card. b blood collections varied in saturation level across blood spots and timepoints. these were classified as “full”, “partial”, and occasionally “empty”. c dbs card yields per blood spot, per timepoint, and per crew member. saliva was collected at the l 92, l 44, l 3, fd1, fd2, fd3, r + 1, r + 45, and r + 82 timepoints using two methods. first, saliva was collected using the omnigene oral kit (ome 505), which preserves nucleic acids (fig. 6a) during the ground timepoints. from these samples, dna, rna, and protein were extracted. dna yield ranged from 28.1 to 3187.8 ng, rna yield from 396.0 to 3544.2 ng (less the two samples had concentrations too low for measurement), and protein concentration from 92.97 to 93.15 ng. a dna, rna, and protein yields from the omnigene oral kits. b volume of crude saliva collected per timepoint. second, crude saliva (i.e., saliva with no preservative added) was collected into a 5 ml dnase/rnase free screw top tube during the ground and flight timepoints. saliva volume varied from 150 to 4000 ul per tube (fig. 6b). crude saliva was also collected during flight (fd2 and fd3), in addition to the ground timepoints. saliva collections have been conducted throughout spaceflight studies for assessing the immune state of crews, particularly in the context of viral reactivation. previously identified viruses that reactivate during spaceflight include epstein barr, varicella zoster, and cytomegalovirus43. responses to reactivation of these viruses can be asymptomatic, debilitating, or even life threatening, thus assessing these adaptations is beneficial in understanding viral spaceflight activity as well as crew health. in addition to viral nucleic acid quantification, numerous biochemical assays can also be performed, including measurements of c reactive protein (crp), cortisol, dehydroepiandrosterone (dhea), and cytokines, among others10,43 46. urine was collected in sterile specimen cups at the l 92, l 44, l 3, r + 1, r + 45, and r + 82 timepoints. specimen cups were collected 1 2 times per day. for preservation, urine was aliquoted and stored at  80 °c. half the urine had zymo urine conditioning buffer (ucb) added before freezing, to preserve nucleic acids. samples yielded 23 155.5 ml of crude urine and 21   112 ml of ucb urine per specimen cup (fig. 7a). urine was split into 1 ml   15 ml aliquots before freezing at  80 °c. a urine volumes per timepoint. volumes are reported for both crude urine and urine preserved with zymo urine conditioning buffer (ucb). b timepoints that stool tubes were collected. “gut” tubes are omnigene•gut tubes for microbiome preservation. “met” tubes are omnimet•gut tubes for metabolome preservation. c stool “gut” tube dna and rna extraction quantities. a wide variety of assays can be performed on urine samples. previous studies have included viral reactivation43,46,47, urinary cortisol48,49, iron and magnesium measurements50 53, bone status54 56, kidney stones54,55, proteomics11, telomere measurements57, and various biomarkers and metabolites17,49,58 61. stool was collected at the l 92, l 44, r + 1, r + 45, and r + 82 timepoints. stool samples were stored into two collection containers at each timepoint, one dna genotek omnigene gut (omr−200) kit with a preservative for metagenomics and another (me−200) with a preservative for metabolomics (fig. 7b). stool was the least consistent sample collected due to the limited windows available for sampling during collection timeframes. dna and rna were extracted from aliquots of the omnigene gut (omr−200) tubes for downstream microbiome analysis. dna yield ranged from 358.5 to 16,660 ng, rna from 690 to 2010 ng (fig. 7c). large variations in yield are attributable to variable stool mass collected between kits. stool samples enable various biochemical, immune, and microbiome changes studies. previous metagenomic assays have found that shannon alpha diversity and richness during long duration missions to the iss62. body swabs were collected at all timepoints. samples were collected by swabbing the body region of interest for 30 seconds, then placing the swab in a sterile 2d matrix tube (thermo scientific #3710) with zymo dna/rna shield preservative. for the first two swab locations, the oral and nasal cavity, the swab was placed directly on the body after removal from its sterile packaging (dry swab method; fig. 8a). for the remaining body locations, the swab was briefly dipped in nuclease free, dna/rna free water before proceeding (wet swab method). eight distinct sites were swabbed with the wet swab method: post auricular, axillary vault, volar forearm, occiput, umbilicus, gluteal crease, glabella, and the toe web space (fig. 8b). the astronaut microbiome has previously been studied in the forehead, forearm, nasal, armpit, navel, postauricular, and tongue body locations, and changes have been documented during flight. changes in alpha diversity and beta diversity were documented, as well as shifts in microbial genera62. however, the impact of these changes on skin health and immunological health are not well understood. a dry swabs were collected from two body locations. b wet swabs were collected from eight body locations. c swabs were collected from the deltoid region. immediately after, 3  or 4 mm skin biopsies were collected from the same area and divided for histology and spatially resolved transcriptomics. acquiring extensive swab samples from the crew skin allows for characterization of the habitat environment, crew skin microbiome adaptations, and interactions with potential human health adaptations resulting from spaceflight exposure. this is very relevant for crew health, considering astronauts become more susceptible to infections during spaceflight missions63, with the relationship between microbe host interactions from spaceflight exposure, which may be a causative factor of astronauts immune dysfunction, which is still not well understood. a skin biopsy on the deltoid was obtained from the l 44 and r + 1 timepoint. biopsies were also collected in advance of a flight to ensure the biopsy site is fully healed before the flight so there is no risk of complication. the wet swab method was used to collect the skin microbiome before the skin biopsy. the skin biopsies were 3 4 millimeters in diameter and were collected for histology and spatially resolved transcriptomics (srt) (fig. 8c). one third of the sample was stored in formalin and kept at room temperature to perform histology. the remaining two thirds of the sample was stored in a cryovial and placed at  80 °c for srt (fig. 8c). this is the first sample collected from astronauts for spatially resolved transcriptomics. the skin is of high interest due to the inflammation related cytokine markers such as il 12p40, il 10, il 17a, and il 1810,17 and skin rash’s status as the most frequent clinical symptom reported during spaceflight64. environmental swabs were collected in flight during the f1 and f2 timepoint. additionally, environmental swabs were collected from the flight simulation capsule at spacex headquarters after days of crew training during the l 92 and l 44 timepoints. environmental swabs were collected using the wet swab method. ten environmental swabs were collected per time point at the following locations in the capsule: an ambient air/control swab, the execute button, the viewing dome, the side hatch mobility aid, the lid of the waste locker, the head section of one of the seats, the commode panel, the right and left sides of the control screen, and the g meter button (fig. 9a d). additionally, the spacecraft’s high efficiency particulate absorbing (hepa) filter was acquired post flight. this filter was cut into 127 rectangular pieces (1.2” x 1.6” x 4”) and stored at −20 °c. a swab locations, descriptions, and label ids. b interior view of the spacex dragon capsule. c view of the control panel located above the middle seats in the dragon capsule. d view of the cupola (viewing dome) region from the outside. the rim of the dome was swabbed from the inside (id 10). previous microbial profiling of spacecraft environments has revealed that equipment sterilized on the ground becomes coated in microbial life in space due to interactions with crew and the introduction of equipment that has not undergone sterilization65. subsequent microbial monitoring assays performed on the iss have detected novel, spaceflight specific species on the iss66. once in space, surface microbes are subject to the unique microgravity and radiation environment of flight, which will influence evolutionary trajectory. the potential impact of this influence on pathogenesis is a concern for long duration space missions, especially given that changes in host pathogen interactions may also be affected during spaceflight67. we report here on biospecimen samples collected from the spacex i4 mission, the most comprehensive human biological specimen collection effort performed on an astronaut cohort to date. the extensive archive of biospecimens included venous blood, dried blood spot cards, saliva, urine, stool, microbiome body swabs, skin biopsies, and environmental capsule swabs. the study objective was to establish a foundational set of methods for biospecimen collection and banking on commercial spaceflight missions suitable for multi omic and molecular analysis. biospecimens were collected to enable comprehensive, multi omic profiles, which can then be used to develop molecular catalogs with higher resolution of human responses to spaceflight. select, targeted measures in clinical labs (clia) were also performed immediately after sample collection (cbc, cmp), and samples and viable cells were preserved in a long term cornell aerospace medicine biobank, such that additional assays and measures can be conducted in the future. great care was put into the standardization of sample processing between field laboratories in hawthorne, cape canaveral, and houston. despite our best efforts to control for all preanalytical variables68, there are some inconsistencies in sample processing that were unavoidable during this mission. of note, there was no access to cold stowage during flight, causing all samples to be stowed at room temperature until they arrived back on earth. of the three sample types collected during flight, two were stable at room temperature (skin/capsule swabs stored in dna/rna shield and capillary blood collected on dried blood spot cards). the third (saliva samples), were not stored in a preservative and, for this reason, will have a distinct profile compared to other timepoints. this limits the context in which these samples will be useful, but will still provide biological insights in more targeted biological studies. we can imagine situations in the future where there will be tradeoffs between standardization of sample collection with previous missions and mission specific constraints influencing the selection of biospecimen collection methods. however, there are several reasons why rigorous biospecimen collection methods for commercial and private spaceflight missions must be developed, which are scalable and translational across populations, missions, and mission parameters. first, little is known about the biological and clinical responses that occur in civilians during and after space travel. while professional astronauts are generally young, healthy, and extensively trained, civilian astronauts have been, and likely will be, far more heterogeneous. they will possess a variety of phenotypes, including older ages, different health backgrounds, and greater medication use, and may experience different medical conditions, risks, and comorbidities. careful molecular characterization will be beneficial for the development of appropriate baseline metrics and countermeasures and, therefore, beneficial for the individual spaceflight experience. in the future, such analyses may enable precision medicine applications aimed at optimizing countermeasures for each individual astronaut who enters and returns safely from space69,70. second, multi omic studies inherently present a large number of measurements within a small set of subjects. these high dimensional datasets present numerous potential challenges with regard to the amplification of noise, risk of overfitting, and false discoveries71. at all times, scientists engaged in multi omic analyses must take special care that true biological variance is what has been measured. the introduction of experimental variance through the progression from sample collection, transport, and storage, to sequencing and analysis can introduce artifacts of variance that render the detection of true biological variance and interpretation of results more difficult. for this reason, tight adherence to experimental controls or annotation at every step of the experimental condition is crucial. careful annotation allows for the assignment of class variables in post hoc analysis. among such applications are the attempt to detect batch effects or determine the impact of variations in temperature (collection, storage, or transport)72. the necessary means to address experimental variance are longitudinal sampling and specimen aliquoting. longitudinal sampling (i.e. collecting numerous serial samples from each test condition) from pre flight, in flight, and post flight allows for greater statistical power when assessing changes attributable to spaceflight. in addition, each sample collected should be divided upon collection into multiple aliquots. this better assures that freeze thaw cycles can be avoided in the analysis stage, as freeze thaw events can introduce considerable experimental variance depending on the molecular class being measured. maintaining all samples at their optimal storage temperature at all times, typically  80 °c or lower (e.g. liquid nitrogen for cells), is crucial73. special attention must be given to how the collection and storage methods in flight vary in relation to the conditions on earth. spaceflight presents considerable differences in the operating environment, where ground conditions are far easier to control than flight. in practice, this may limit the types of samples that can be collected during flight. third, rigorous methods must be developed and followed to pursue comparisons across missions with varying design parameters. in this consideration, there is an argument for the development of specimen collection, transport, storage, processing, analysis, and reporting standards. at the same time, this must be balanced with the flexibility required for innovation since standards can sometimes limit advancement in methodology. in the present study, common methods were used for the i4 and the polaris dawn and axiom 2 missions. however, selected methods may require optimization for polaris dawn like missions, to increase the yields during sample processing and adapt to unique parameters imposed by the anticipated spacewalk (extravehicular activity; eva). moreover, within standards or best practices, unique research for each mission may require alteration of previously successful methods. with these considerations in mind, we must balance methodology standardization with advances in methodology options and mission specific objectives. as the commercial spaceflight sector gains momentum and more astronauts with different health profiles and backgrounds have access to space, comprehensive data on the biological impact of short duration spaceflight is of paramount importance. such data will further expand our understanding and knowledge of how spaceflight affects human physiology, microbial adaptations, and environmental biology. the use of integrative omics technologies for civilian astronauts has revealed novel responses across genomics, proteomics, metabolomics, microbiome, and transcriptomics measures74 83. creating multi omic datasets from spaceflight studies on astronaut cohorts will further advance our understanding, inform future mission planning, and help discover what appropriate countermeasures can be developed to minimize future risk and enhance performance. validating sample collection methodologies initially in short duration commercial spaceflight is a key step for future human health research in long duration and exploration class missions to the moon and beyond. to help meet these challenges, we have established the soma protocols, which detail standard multi omic measures of astronaut health and protocols for sample collection from astronaut cohorts. although the all civilian i4 crew pioneered the first use of the soma protocols, the methodology outlined here is robust and generalizable, making it applicable to future astronaut crews from any commercial mission provider (e.g., spacex, axiom space, sierra space, blue origin) or space agencies (nasa, esa, jaxa, roscosmos). furthermore, the soma banking, sequencing, and processing methods are a springboard for continuing biospecimen analysis and expanding our knowledge of multi omic dynamics before, during, and after human spaceflight missions, providing a molecular roadmap for crew health, medical biometrics, and possible countermeasures. venipuncture was performed on each subject using a bd vacutainer® safety lok™ blood collection set (bd biosciences, #367281) and a vacutainer one use holder (bd biosciences, 364815). the puncture site was located near the cubital fossa and was sterilized with a bzk antiseptic towelette (dynarex, reorder no. 1303). blood was collected into 1 serum separator tube (sst, bd biosciences: #367987, lot: #1158449, #1034773), 2 cell processing tubes (cpt, bd biosciences: #362753, lot: #1133477, #1012161), 1 blood rna tube (brna, paxgene: #762165, lot: #1021333), 1 cell free dna bct (cfdna bct, streck: #230470, lot: #11530331), and 4 k2 edta blood collection tubes (bd biosciences, #367844, lot: #0345756) per crew member per time point. for samples collected in hawthorne, blood was drawn at spacex headquarters, then immediately transported to usc for processing. samples collected at cape canaveral were processed on site. for processing, serum separator tubes (sst) were centrifuged at 1300x g for 10 minutes. 500ul aliquots of serum were aliquoted into 1 ml matrix 2d screw tubes (thermofisher, 3741 wp1d br) and stored at  80 °c. sst tubes were recapped and stored at −20 °c to preserve the red blood cell pellet. cell processing tubes were centrifuged at 1800xg for 30 minutes. plasma was aliquoted into 1 ml matrix 2d screw tubes and stored at  80 °c. 5 ml of 2% fbs (thermofisher, #26140079) in pbs (thermofisher, #10010023) was added to the cpt tube to resuspend pbmcs. pbmc suspension was transferred to a clean 15 ml conical tube. the total volume was brought to 15 ml with 2% fbs in pbs. the tube was centrifuged for 15 minutes at 300x g. supernatant was discarded. pbmcs were resuspended 6 ml of 10% dmso (millipore sigma, #d4540 500ml) in fbs. 1 ml of pbmcs were moved to 6 cryogenic vials (corning, #8672). cryovials were placed in a mr. frostytm (thermofisher, #5100 0001) and stored at  80 °c. cpts were recapped and stored at −20 °c to preserve the red blood cell pellet. there was one outlier to this sample collection, the r + 194 timepoint, where cpt sodium citrate tubes were used (bd biosciences, cat no. 362760). cfdna bcts were centrifuged at 300xg for 20 minutes. plasma was transferred to a 15 ml conical tube. plasma was centrifuged 5000xg for 10 minutes. 500ul aliquots of plasma were aliquoted into 1 ml matrix 2d screw tubes and stored at  80 °c. cfdna bcts were recapped and stored at −20 °c to preserve the red blood cell pellet. paxgene blood rna tubes were processed according to the manufacturer’s instructions. briefly, tubes were left upright for a minimum of 2 hours before freezing at −20 °c. for rna extraction, tubes were thawed and processed with the paxgene blood rna kit (qiagen, #762164). one 4 ml k2 edta tube was shipped on ice overnight to wcm for processing. blood was centrifuged at 500x g for 10 minutes, then plasma was transferred to a new tube and centrifuged at 3000 x g for 20 minutes, and the supernatant was collected and stored at  80 °c for evp isolation. plasma volumes ranged between 0.6   1.7 ml. plasma was later thawed for downstream processing, when concentrations were measured. plasma samples were thawed on ice, and evps were isolated by sequential ultracentrifugation (hoshino et al., 2020). samples were centrifuged at 12,000x g for 20 minutes to remove microvesicles, then evps were collected by ultracentrifugation in a beckman coulter optima xe or xpe ultracentrifuge at 100,000x g for 70 minutes. evps were then washed in pbs and pelleted again by ultracentrifugation at 100,000x g for 70 minutes. the final evp pellet was resuspended in pbs. crew members warmed their hands and massaged their finger towards the fingertip to enrich blood flow toward the puncture site. the puncture site was sterilized using a bzk antiseptic towelette (dynarex, reorder no. 1303). skin was punctured using a contact activated lancet (bd biosciences, #366593) or a 21 gauge needle (bd biosciences, #305167), depending on crew member preference. capillary blood was collected onto the whatman 903 protein saver dbs cards (cytiva, #10534612). blood was transferred by touching only the blood droplet to the surface of the dbs card. dbs cards were stored at room temperature with a desiccant pack (cytiva, #10548239). to collect crude saliva, crew members uncapped and spit into a sterile, pcr clean, 5 ml screw cap tube (eppendorf, 30122330). crew spit repeatedly until at least 1 ml was collected. saliva was transported to a sterile flow hood and separated into 500ul aliquots. aliquots were frozen at  80 °c. to collect preserved saliva, crew members used the omnigene oral kit (ome 505). crew members spit into the kit’s tube until they reached the fill line. the tube was re capped, which released the preservative liquid. tubes were inverted to mix the saliva and preservative before being placed at −20 °c for storage. after all timepoints were collected, dna, rna, and protein were extracted using the allprep dna/rna/protein kit (qiagen, #47054). sample concentrations were measured with qubit high sensitivity dsdna and rna platform. proteins were quantified with the pierce™ rapid gold bca protein assay kit (thermo scientific, #a53225) on promega glomax plate reader. crew members urinated into sterile specimen containers (thermo scientific, #13 711 56). the container was stored at 4 c until it was prepared for long term storage. to prepare urine samples for long term storage, urine was aliquoted into 1 ml, 15 ml, and 50 ml tubes. half of the urine was immediately placed at −80 °c. the other half had urine conditioning buffer (zymo, #d3061 1 140) added to the sample before placing in the  80 °c freezer. crew members isolated a stool sample using a paper toilet accessory (dna genotek, om ac1). stool was transferred into and omnigene•gut tube (dnagenotek, omr−200) and an omnimet•gut tube (dna genotek, me−200). tubes were placed at  80 °c for long term storage. for nucleic acid extraction, 200ul of each tube was allocated for dna extraction with the qiagen powerfecal pro kit and 200ul was allocated to rna extraction with the qiagen powerviral kit. the remaining sample was split into 500ul aliquots and re stored at  80 °c. crew members put on gloves and remove a sterile dna/rna swab (isohelix, sk 4s) from its packaging. for collection of the postauricular, axillary vault, volar forearm, occiput, umbilicus, gluteal crease, glabella, toe web space, and capsule environment regions, swabs were dipped in nuclease free water (this step was skipped for oral and nasal swabs) for ground collections. for in flight collections, hfactor hydrogen infused water was used in place of nuclease free water. each body location was swabbed for 30 seconds, using both sides of the swab. swabs were then placed in 1 ml matrix 2d screw tubes containing 400ul of dna/rna shield (zymo). the tip of the swab was broken off so that only the swab tip was stored in the matrix 2d screw tube. tubes were stored at 4 c. skin biopsies were performed on the deltoid region of the arm. each site was prepared by application of chloraprep and anesthesia was induced with administration of 1% lidocaine with 1:100,000 epinephrine. a trephine punch was used to remove a 3  or 4 mm diameter piece of skin. the resected piece was cut into approximately 1/3 and 2/3 sections. the smaller piece was added to a formalin filled specimen jar. the larger piece was placed in a cryovial and stored at  80 °c. surgical defects were closed with 1 or 2 5 0 or 4 0 nylon sutures. hepa filter was taken apart and sectioned under a chemical hood to avoid contamination. the filter contained two parts, an activated carbon component and a hepa filter. the activated carbon component was discarded and the filter was sectioned using a sterile blade. sections were placed in individual specimen containers and stored at −20 °c. all subjects were consented and samples were collected and processed under the approval of the irb at weill cornell medicine, under protocol 21 05023569. figures 1c, 2c, 3, 5a, 8 were created with biorender.com released under a ‘creative commons attribution noncommercial noderivs 4.0 international license’. plots were generated in r using ggplot2. further information on research design is available in the nature portfolio reporting summary linked to this article. we thank the scientific computing unit (scu) at wcm and the genomics, epigenomics, and biorepository cores. cem thanks the nih (r01mh117406, r01es032638) and nasa (nnx14ah50g, nnx17ab26g, 80nssc22k0254, nnh18ztt001n fg2, 80nssc23k0832), the lls (mcl7001 18, lls 9238 16, 7029 23), as well as igor tulchinsky and the worldquant foundation, the gi research foundation (girf), the radvinsky/chudnovsky family. ego thanks nasa bps (80nssc23k0832). we thank jj hastings for protocol work. jk thanks mogam science foundation and was supported by the basic science research program through the national research foundation of korea (nrf) funded by the ministry of education (rs−2023 00241586). jk acknowledges boryung for their financial support and research enhancement ground, provided through their global space healthcare initiative, humans in space, including mentorship and access to relevant expert networks. we also thank jennifer conrad for cpt photography. c.e.m., j.m., m.m. led study conceptualization. c.e.m., j.m., m.m., e.g.o., s.m. developed study methodology. c.e.m., m.y., j.m., and d.l. acquired resources and funding. c.e.m., j.m., and e.g.o. administered the project. e.g.o., k.r., b.t.t., r.k., v.o., s.m., and r.d.g. performed off site sample collection protocols. j.k., i.m., l.p., n.d., d.n., j.w.h., j.s.g.m., j.p., m.m.s., and a.s.k. performed sample processing at weill cornell medicine. c.e.m. and e.e.a. led institutional review board (irb) protocol development. e.g.o., m.m., and l.i. developed figures. e.g.o. and j.c.s. drafted the manuscript. s.a.n., c.m.s., m.a.s., and b.s. reviewed and edited the manuscript. nature communications thanks christina ellervik and christina ellervik for their contribution to the peer review of this work. a peer review file is available. images of the inspiration4 and dragon capsule are available from the spacex flickr account (https://www.flickr.com/people/spacex/). this was the source image data used to label the dragon swab location in fig. 9. cem is co founder of cosmica biosciences. btt is compensated for consulting with seed health and enzymetrics biosciences on microbiome study design and holds an ownership stake in the former. cms, jcs, and mas hold shares in sovaris holdings, llc. my is the founder and president of cantracer biosciences inc. authors not listed here do not have competing interests. publisher’s note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. the online version contains supplementary material available at 10.1038/s41467 024 48806 z. this section collects any data citations, data availability statements, or supplementary materials included in this article. images of the inspiration4 and dragon capsule are available from the spacex flickr account (https://www.flickr.com/people/spacex/). this was the source image data used to label the dragon swab location in fig. 9. articles from nature communications are provided here courtesy of nature publishing group connect with nlm national library of medicine 8600 rockville pike bethesda, md 20894
supported by an extensive examination of medical data gathered from the private inspiration4 mission in 2021 revealed temporary cognitive declines and genetic changes in the crew. by kenneth chang space changes you, even during short trips off the planet. four people who spent three days off earth in september 2021 experienced physical and mental changes that included modest declines in cognitive tests, stressed immune systems and genetic changes within their cells, scientists report in a package of papers published on tuesday in the journal nature and several other related journals. almost all of what changed in the astronauts returned to normal after they splashed down on earth. none of the alterations appeared to pose a showstopping caution for future space travelers. but the results also highlighted how little medical researchers know. christopher mason, a professor of genomics, physiology and biophysics at weill cornell medicine in new york city and one of the leaders of the research, called the collection of papers and data “the most in depth examination we’ve ever had of a crew” as he spoke during a news conference on monday. the four astronauts traveled on a mission, known as the inspiration4, which was the first trip to orbit where not one of the crew members was a professional astronaut. jared isaacman, a billionaire entrepreneur, led the mission. instead of bringing friends along, he recruited three travelers who represented a wider swath of society: hayley arceneaux, a physician assistant who survived cancer during her childhood; sian proctor, a community college professor who teaches geoscience; and christopher sembroski, an engineer. the inspiration4 crew members consented to participating in medical experiments   collecting samples of blood, urine, feces and saliva during their flight   and to allowing the data to be cataloged in an online archive known as the space omics and medical atlas, or soma, which is publicly available. although the data is anonymous, that does not provide much privacy because there were only four crew members on inspiration4. “you could probably figure out who is who, actually,” dr. proctor said in an interview.

 a new database aims to pave the way for a better understanding of space health and medicine as more civilian missions launch. over the past five decades, under 700 humans have flown in space. nearly every one of those humans were professionally trained astronauts and in similar peak physical condition. and most of those astronauts were men. but in 2021, the first space mission with four civilian astronauts   meaning, not government agency astronauts   flew. it opened a new path for the scientists who study the effects of spaceflight on human biology. on june 11, 2024, more than 200 of those researchers published a suite of 44 papers across multiple nature journals.