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10.1101/003467
|
Epigenetic Modifications are Associated with Inter-species Gene Expression Variation in Primates
|
Xiang Zhou;Carolyn Cain;Marsha Myrthil;Noah Lewellen;Katelyn Michelini;Emily Davenport;Matthew Stephens;Jonathan Pritchard;Yoav Gilad;
|
Yoav Gilad
|
University of Chicago
|
2014-03-19
|
1
|
New Results
|
cc_no
|
Genomics
|
https://www.biorxiv.org/content/early/2014/03/19/003467.source.xml
|
Changes in gene regulation level have long been thought to play an important role in evolution and speciation, especially in primates. Over the past decade, comparative genomic studies have revealed extensive inter-species differences in gene expression levels yet we know much less about the extent to which regulatory mechanisms differ between species. To begin addressing this gap, we performed a comparative epigenetic study in primate lymphoblastoid cell lines (LCLs), to query the contribution of RNA polymerase II (Pol II) and four histone modifications (H3K4me1, H3K4me3, H3K27ac, and H3K27me3) to inter-species variation in gene expression levels. We found that inter-species differences in mark enrichment near transcription start sites are significantly more often associated with inter-species differences in the corresponding gene expression level than expected by chance alone. Interestingly, we also found that first-order interactions among the histone marks and Pol II do not markedly contribute to the degree of association between the marks and inter-species variation in gene expression levels, suggesting that the marginal effects of the five marks dominate this contribution.
|
10.1186/s13059-014-0547-3
|
biorxiv
| 351 |
10.1101/003475
|
Divide and Conquer approach for Genome Classification based on subclass characterization
|
Siddanagouda Somanagouda Patil;Narasimha Murty Musti;Ulavappa Basvanneppa Angadi;
|
Siddanagouda Somanagouda Patil
|
University of Agricultural Sciences
|
2014-03-20
|
1
|
New Results
|
cc_no
|
Bioinformatics
|
https://www.biorxiv.org/content/early/2014/03/20/003475.source.xml
|
Classification of large grass genome sequences has major challenges in functional genomes. The presence of motifs in grass genome chains can make the prediction of the functional behavior of grass genome possible. The correlation between grass genome properties and their motifs is not always obvious, since more than one motif may exist within a genome chain. Due to the complexity of this association most pattern classification algorithms are either vain or time consuming. Attempted to a reduction of high dimensional data that utilizes DAC technique is presented. Data are disjoining into equal multiple sets while preserving the original data distribution in each set. Then, multiple modules are created by using the data sets as independent training sets and classified into respective modules. Finally, the modules are combined to produce the final classification rules, containing all the previously extracted information. The methodology is tested using various grass genome data sets. Results indicate that the time efficiency of our algorithm is improved compared to other known data mining algorithms.
|
NA
|
biorxiv
| 352 |
10.1101/003517
|
Towards a new history and geography of human genes informed by ancient DNA
|
Joseph Pickrell;David Reich;
|
Joseph Pickrell
|
New York Genome Center
|
2014-03-21
|
1
|
New Results
|
cc_no
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/03/21/003517.source.xml
|
Genetic information contains a record of the history of our species, and technological advances have transformed our ability to access this record. Many studies have used genome-wide data from populations today to learn about the peopling of the globe and subsequent adaptation to local conditions. Implicit in this research is the assumption that the geographic locations of people today are informative about the geographic locations of their ancestors in the distant past. However, it is now clear that long-range migration, admixture and population replacement have been the rule rather than the exception in human history. In light of this, we argue that it is time to critically re-evaluate current views of the peopling of the globe and the importance of natural selection in determining the geographic distribution of phenotypes. We specifically highlight the transformative potential of ancient DNA. By accessing the genetic make-up of populations living at archaeologically-known times and places, ancient DNA makes it possible to directly track migrations and responses to natural selection.
|
10.1016/j.tig.2014.07.007
|
biorxiv
| 353 |
10.1101/003483
|
Identification of five patterns of nucleosome positioning that globally describe transcription factor function
|
Kazumitsu Maehara;Yasuyuki Ohkawa;
|
Yasuyuki Ohkawa
|
Kyushu University
|
2014-03-21
|
1
|
New Results
|
cc_by_nc
|
Molecular Biology
|
https://www.biorxiv.org/content/early/2014/03/21/003483.source.xml
|
Following the binding of transcription factors (TF) to specific regions, chromatin remodeling including alterations in nucleosome positioning (NP) occurs. These changes in NP cause selective gene expression to determine cell function. However whether specific NP patterns upon TF binding determine the transcriptional regulation such as gene activation or suppression is unclear. Here we identified five patterns of NP around TF binding sites (TFBSs) using fixed MNase-Seq analysis. The most frequently observed NP pattern described the transcription state. The five patterns explained approximately 80% of the whole NP pattern on the genome in mouse C2C12 cells. We further performed ChIP-Seq using the input obtained from the fixed MNase-Seq. The result showed that a single trial of ChIP-Seq could visualize the NP patterns around the TFBS and predict the function of the transcriptional regulation at the same time. These findings indicate that NP can directly predict the function of TFs.
|
NA
|
biorxiv
| 354 |
10.1101/003525
|
Towards a molecular systems model of coronary artery disease
|
Gad Abraham;Oneil G Bhalala;Paul IW de Bakker;Samuli Ripatti;Michael Inouye;
|
Michael Inouye
|
Medical Systems Biology, Department of Pathology and Department of Microbiology & Immunology, The Un
|
2014-03-23
|
1
|
New Results
|
cc_by
|
Systems Biology
|
https://www.biorxiv.org/content/early/2014/03/23/003525.source.xml
|
Coronary artery disease (CAD) is a complex disease driven by myriad interactions of genetics and environmental factors. Traditionally, studies have analyzed only one disease factor at a time, providing useful but limited understanding of the underlying etiology. Recent advances in cost-effective and high-throughput technologies, such as single nucleotide polymorphism (SNP) genotyping, exome/genome sequencing, gene expression microarrays and metabolomics assays have enabled the collection of millions of data points in many thousands of individuals. In order to make sense of such omics data, effective analytical methods are needed. We review and highlight some of the main results in this area, focusing on integrative approaches that consider multiple modalities simultaneously. Such analyses have the potential to uncover the genetic basis of CAD, produce genomic risk scores (GRS) for disease prediction, disentangle the complex interactions underlying disease, and predict response to treatment.
|
10.1007/s11886-014-0488-1
|
biorxiv
| 355 |
10.1101/003491
|
Response to a population bottleneck can be used to infer recessive selection
|
Daniel J Balick;Ron Do;David Reich;Shamil R Sunyaev;
|
Shamil R Sunyaev
|
Brigham & Women's Hospital, Harvard Medical School
|
2014-03-21
|
1
|
New Results
|
cc_by_nc_nd
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/03/21/003491.source.xml
|
Here we present the first genome wide statistical test for recessive selection. This test uses explicitly non-equilibrium demographic differences between populations to infer the mode of selection. By analyzing the transient response to a population bottleneck and subsequent re-expansion, we qualitatively distinguish between alleles under additive and recessive selection. We analyze the response of the average number of deleterious mutations per haploid individual and describe time dependence of this quantity. We introduce a statistic, BR, to compare the number of mutations in different populations and detail its functional dependence on the strength of selection and the intensity of the population bottleneck. This test can be used to detect the predominant mode of selection on the genome wide or regional level, as well as among a sufficiently large set of medically or functionally relevant alleles.
|
NA
|
biorxiv
| 356 |
10.1101/001305
|
Ordered, Random, Monotonic, and Non-Monotonic Digital Nanodot Gradients
|
Grant Ongo;Sebastien G Ricoult;Timothy E Kennedy;David Juncker;
|
David Juncker
|
McGill University
|
2014-03-28
|
3
|
New Results
|
cc_by
|
Bioengineering
|
https://www.biorxiv.org/content/early/2014/03/28/001305.source.xml
|
Cell navigation is directed by inhomogeneous distributions of extracellular cues. It is well known that noise plays a key role in biology and is present in naturally occurring gradients at the micro- and nanoscale, yet it has not been studied with gradients in vitro. Here, we introduce novel algorithms to produce ordered and random gradients of discrete nanodots - called digital nanodot gradients (DNGs) - according to monotonic and non-monotonic density functions. The algorithms generate continuous DNGs, with dot spacing changing in two dimensions along the gradient direction according to arbitrary mathematical functions, with densities ranging from 0.02% to 44.44%. The random gradient algorithm compensates for random nanodot overlap, and the randomness and spatial homogeneity of the DNGs were confirmed with Ripleys K function. An array of 100 DNGs, each 400 x 400 {micro}m2, comprising a total of 57 million 200 x 200 nm2 dots was designed and patterned into silicon using electron-beam lithography, then patterned as fluorescently labeled IgGs on glass using lift-off nanocontact printing. DNGs will facilitate the study of the effects of noise and randomness at the micro- and nanoscales on cell migration and growth.
|
10.1371/journal.pone.0106541
|
biorxiv
| 357 |
10.1101/001255
|
Broad-scale spatial patterns of canopy cover and pond morphology affect the structure of a Neotropical amphibian metacommunity
|
Diogo B. Provete;Thiago Gonçalves-Souza;Michel Garey;Itamar A. Martins;Denise Rossa-Feres;
|
Diogo B. Provete
|
Universidade Federal de Goiás
|
2014-04-09
|
2
|
New Results
|
cc_by_nc_nd
|
Ecology
|
https://www.biorxiv.org/content/early/2014/04/09/001255.source.xml
|
Spatial and environmental processes influence species composition at distinct scales. Previous studies suggested that the landscape-scale distribution of larval anurans is influenced by environmental gradients related to adult breeding site selection, such as pond canopy cover, but not water chemistry. However, the combined effects of spatial, pond morphology, and water chemistry variables on metacommunity structure of larval anurans have not been analyzed. We used a partial redundancy analysis with variation partitioning to analyze the relative influence of pond morphology (e.g., depth, area, and aquatic vegetation), water chemistry, and spatial variables on a tadpole metacommunity from southeastern Brazil. We predict that the metacommunity will be spatially structured at broad spatial scales, while environmental variables, mainly related to adult habitat selection, would play a larger role at fine spatial scales. We found that broad-scale spatial patterns of pond canopy cover and pond morphology strongly influenced metacommunity structure. Additionally, species composition was spatially autocorrelated at short distances. We suggest that the reproductive behavior of adult anurans is driving tadpole metacommunity dynamics, since pond morphology, but not water chemistry affects breeding site selection by adults. Our results contribute to the understanding of amphibian species diversity in tropical environments.
|
10.1007/s10750-014-1870-0
|
biorxiv
| 360 |
10.1101/001552
|
Ancient human genomes suggest three ancestral populations for present-day Europeans
|
Iosif Lazaridis;Nick Patterson;Alissa Mittnik;Gabriel Renaud;Swapan Mallick;Karola Kirsanow;Peter H. Sudmant;Joshua G. Schraiber;Sergi Castellano;Mark Lipson;Bonnie Berger;Christos Economou;Ruth Bollongino;Qiaomei Fu;Kirsten Bos;Susanne Nordenfelt;Heng Li;Cesare de Filippo;Kay Prüfer;Susanna Sawyer;Cosimo Posth;Wolfgang Haak;Fredrik Hallgren;Elin Fornander;Nadin Rohland;Dominique Delsate;Michael Francken;Jean-Michel Guinet;Joachim Wahl;George Ayodo;Hamza A. Babiker;Graciela Baillet;Elena Balanovska;Oleg Balanovsky;Ramiro Barrantes;Gabriel Bedoya;Haim Ben-Ami;Judit Bene;Fouad Berrada;Claudio M.
|
Johannes Krause
|
Institute for Archaeological Sciences, University of Tübingen
|
2014-04-05
|
4
|
New Results
|
cc_by_nc_nd
|
Genetics
|
https://www.biorxiv.org/content/early/2014/04/05/001552.source.xml
|
We sequenced genomes from a [~]7,000 year old early farmer from Stuttgart in Germany, an [~]8,000 year old hunter-gatherer from Luxembourg, and seven [~]8,000 year old hunter-gatherers from southern Sweden. We analyzed these data together with other ancient genomes and 2,345 contemporary humans to show that the great majority of present-day Europeans derive from at least three highly differentiated populations: West European Hunter-Gatherers (WHG), who contributed ancestry to all Europeans but not to Near Easterners; Ancient North Eurasians (ANE), who were most closely related to Upper Paleolithic Siberians and contributed to both Europeans and Near Easterners; and Early European Farmers (EEF), who were mainly of Near Eastern origin but also harbored WHG-related ancestry. We model these populations deep relationships and show that EEF had [~]44% ancestry from a \"Basal Eurasian\" lineage that split prior to the diversification of all other non-African lineages.
|
10.1038/nature13673
|
biorxiv
| 363 |
10.1101/001453
|
Selection signatures in worldwide Sheep populations
|
Maria-Ines Fariello;Bertrand Servin;Gwenola Tosser-Klopp;Rachelle Rupp;Carole Moreno;International Sheep Genomics Consortium n.a.;Magali San Cristobal;simon boitard;
|
simon boitard
|
INRA
|
2014-04-11
|
2
|
New Results
|
cc_by_nc_nd
|
Genetics
|
https://www.biorxiv.org/content/early/2014/04/11/001453.source.xml
|
The diversity of populations in domestic species offer great opportunities to study genome response to selection. The recently published Sheep Hapmap dataset is a great example of characterization of the world wide genetic diversity in the Sheep. In this study, we re-analyzed the Sheep Hapmap dataset to identify selection signatures in worldwide Sheep populations. Compared to previous analyses, we make use of statistical methods that (i) take account of the hierarchical structure of sheep populations, (ii) make use of Linkage Disequilibrium information and (iii) focus specifically on either recent or older selection signatures. We show that this allows to pinpoint several new selection signatures in the sheep genome and to distinguish those related to modern breeding objectives and to earlier post-domestication constraints. The newly identified regions, together with the one previously identified, reveal the extensive genome response to selection on morphology, color and adaptation to new environments.
|
10.1371/journal.pone.0103813
|
biorxiv
| 364 |
10.1101/000869
|
Virulence in a Pseudomonas syringae Strain with a Small Repertoire of Predicted Effectors
|
Kevin L Hockett;Marc T Nishimura;Erick Karlsrud;Kevin Dougherty;David A Baltrus;
|
David A Baltrus
|
University of Arizona
|
2014-04-21
|
2
|
New Results
|
cc_no
|
Microbiology
|
https://www.biorxiv.org/content/early/2014/04/21/000869.source.xml
|
Both type III effector proteins and non-ribosomal peptide toxins play important roles for Pseudomonas syringae pathogenicity in host plants, but whether and how these virulence pathways interact to promote infection remains unclear. Genomic evidence from one clade of P. syringae suggests a tradeoff between the total number of type III effector proteins and presence of syringomycin, syringopeptin, and syringolin A toxins. Here we report the complete genome sequence from P. syringae CC1557, which contains the lowest number of known type III effectors to date and has also acquired genes similar to sequences encoding syringomycin pathways from other strains. We demonstrate that this strain is pathogenic on Nicotiana benthamiana and that both the type III secretion system and a new type III effector family, hopBJ1, contribute to virulence. We further demonstrate that virulence activity of HopBJ1 is dependent on similar catalytic sites as the E. coli CNF1 toxin. Taken together, our results provide additional support for a negative correlation between type III effector repertoires and the potential to produce syringomycin-like toxins while also highlighting how genomic synteny and bioinformatics can be used to identify and characterize novel virulence proteins.
|
NA
|
biorxiv
| 365 |
10.1101/001214
|
Conneconomics: The Economics of Dense, Large-Scale, High-Resolution Neural Connectomics
|
Adam H Marblestone;Evan R Daugharthy;Reza Kalhor;Ian D Peikon;Justus M Kebschull;Seth L Shipman;Yuriy Mishchenko;Je Hyuk Lee;David A Dalrymple;Bradley M Zamft;Konrad P Kording;Edward S Boyden;Anthony M Zador;George M Church;
|
Adam H Marblestone
|
Harvard University
|
2014-04-21
|
4
|
New Results
|
cc_by_nc_nd
|
Neuroscience
|
https://www.biorxiv.org/content/early/2014/04/21/001214.source.xml
|
We analyze the scaling and cost-performance characteristics of current and projected connectomics approaches, with reference to the potential implications of recent advances in diverse contributing fields. Three generalized strategies for dense connectivity mapping at the scale of whole mammalian brains are considered: electron microscopic axon tracing, optical imaging of combinatorial molecular markers at synapses, and bulk DNA sequencing of trans-synaptically exchanged nucleic acid barcode pairs. Due to advances in parallel-beam instrumentation, whole mouse brain electron microscopic image acquisition could cost less than $100 million, with total costs presently limited by image analysis to trace axons through large image stacks. Optical microscopy at 50-100 nm isotropic resolution could potentially read combinatorially multiplexed molecular information from individual synapses, which could indicate the identifies of the pre-synaptic and post-synaptic cells without relying on axon tracing. An optical approach to whole mouse brain connectomics may be achievable for less than $10 million and could be enabled by emerging technologies to sequence nucleic acids in-situ in fixed tissue via fluorescent microscopy. Novel strategies relying on bulk DNA sequencing, which would extract the connectome without direct imaging of the tissue, could produce a whole mouse brain connectome for $100k-$1 million or a mouse cortical connectome for $10k-$100k. Anticipated further reductions in the cost of DNA sequencing could lead to a $1000 mouse cortical connectome.
|
NA
|
biorxiv
| 366 |
10.1101/000943
|
Simultaneous optogenetic manipulation and calcium imaging in freely moving C. elegans
|
Frederick B. Shipley;Christopher M. Clark;Mark J. Alkema;Andrew M. Leifer;
|
Andrew M. Leifer
|
Princeton University
|
2014-04-02
|
3
|
New Results
|
cc_by_nc
|
Neuroscience
|
https://www.biorxiv.org/content/early/2014/04/02/000943.source.xml
|
Editor:\n\nA fundamental goal of systems neuroscience is to probe the dynamics of neural activity that generate behavior. Here we present an instrument to simultaneously manipulate and monitor neural activity and behavior in the freely moving nematode Caenorhabditis elegans. We use the instrument to directly observe the relationship between sensory neuron activation, interneuron dynamics and locomotion in the mechanosensory circuit.\n\nPreviously in this journal, we presented an optogenetic illumination system capable of real-time light delivery with high spatial resolution to stimulate or inhibit specified targets in freely moving C. elegans [1]. This \"Colbert\" system and others like it [2] have been instrumental in defining neural coding of several behaviors in C. elegans including chemotaxis [3], nociception [4] and the escape response [5]. Here we integrate the Colbert s ...
|
10.3389/fncir.2014.00028
|
biorxiv
| 367 |
10.1101/000521
|
Pathways to social evolution: reciprocity, relatedness, and synergy
|
Jeremy Van Cleve;Erol Akcay;
|
Jeremy Van Cleve
|
National Evolutionary Synthesis Center
|
2014-04-17
|
2
|
New Results
|
cc_by_nc_nd
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/04/17/000521.source.xml
|
Many organisms live in populations structured by space and by class, exhibit plastic responses to their social partners, and are subject to non-additive ecological and fitness effects. Social evolution theory has long recognized that all of these factors can lead to different selection pressures but has only recently attempted to synthesize how these factors interact. Using models for both discrete and continuous phenotypes, we show that analyzing these factors in a consistent framework reveals that they interact with one another in ways previously overlooked. Specifically, behavioral responses (reciprocity), genetic relatedness, and synergy interact in non-trivial ways that cannot be easily captured by simple summary indices of assortment. We demonstrate the importance of these interactions by showing how they have been neglected in previous synthetic models of social behavior both within and between species. These interactions also affect the level of behavioral responses that can evolve in the long run; proximate biological mechanisms are evolutionarily stable when they generate enough responsiveness relative to the level of responsiveness that exactly balances the ecological costs and benefits. Given the richness of social behavior across taxa, these interactions should be a boon for empirical research as they are likely crucial for describing the complex relationship linking ecology, demography, and social behavior.
|
10.1111/evo.12438
|
biorxiv
| 368 |
10.1101/000075
|
A Scalable Formulation for Engineering Combination Therapies for Evolutionary Dynamics of Disease
|
Vanessa Jonsson;Anders Rantzer;Richard M Murray;
|
Vanessa Jonsson
|
Caltech
|
2014-03-30
|
2
|
New Results
|
cc_by_nc
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/03/30/000075.source.xml
|
It has been shown that optimal controller synthesis for positive systems can be formulated as a linear program. Leveraging these results, we propose a scalable iterative algorithm for the systematic design of sparse, small gain feedback strategies that stabilize the evolutionary dynamics of a generic disease model. We achieve the desired feedback structure by augmenting the optimization problems with {ell}1 and {ell}2 regularization terms, and illustrate our method on an example inspired by an experimental study aimed at finding appropriate HIV neutralizing antibody therapy combinations in the presence of escape mutants.
|
10.1109/ACC.2014.6859452
|
biorxiv
| 369 |
10.1101/002675
|
Non-specificity of Pitstop 2 in clathrin-mediated endocytosis
|
Anna K Willox;Yasmina M.E. Sahraoui;Stephen J Royle;
|
Stephen J Royle
|
University of Warwick
|
2014-04-15
|
2
|
New Results
|
cc_by
|
Cell Biology
|
https://www.biorxiv.org/content/early/2014/04/15/002675.source.xml
|
Small molecule inhibitors of clathrin-mediated endocytosis are highly desired for the dissection of membrane trafficking pathways in the lab and for potential use as anti-infectives in the clinic. One inhibition strategy is to prevent clathrin from contacting adaptor proteins so that clathrin-mediated endocytosis cannot occur. \"Pitstop\" compounds have been developed which block only one of the four functional interaction sites on the N-terminal domain of clathrin heavy chain. Despite this limitation, Pitstop 2 causes profound inhibition of clathrin-mediated endocytosis. In this study, we probed for non-specific activity of Pitstop 2 by examining its action in cells expressing clathrin heavy chain harbouring mutations in the N-terminal domain interaction sites. We conclude that the inhibition observed with this compound is due to non-specificity, i.e. it causes inhibition away from its proposed mode of action. We recommend that these compounds be used with caution in cells and that they should not be used to conclude anything of the function of clathrins N-terminal domain.
|
10.1242/bio.20147955
|
biorxiv
| 371 |
10.1101/002659
|
Synthesis and patterning of tunable multiscale materials with engineered cells
|
Allen Y Chen;Urartu O.S. Seker;Michelle Y Lu;Robert J Citorik;Timothy Lu;
|
Timothy Lu
|
Massachusetts Institute of Technology
|
2014-03-27
|
2
|
New Results
|
cc_no
|
Synthetic Biology
|
https://www.biorxiv.org/content/early/2014/03/27/002659.source.xml
|
A major challenge in materials science is to create self-assembling, functional, and environmentally responsive materials which can be patterned across multiple length scales. Natural biological systems, such as biofilms, shells, and skeletal tissues, implement dynamic regulatory programs to assemble complex multiscale materials comprised of living and non-living components1-9. Such systems can provide inspiration for the design of heterogeneous functional systems which integrate biotic and abiotic materials via hierarchical self-assembly. Here, we present a synthetic-biology platform for synthesizing and patterning self-assembled functional amyloid materials across multiple length scales with bacterial biofilms. We engineered Escherichia coli curli amyloid production under the tight control of synthetic regulatory circuits and interfaced amyloids with inorganic materials to create a biofilm-based electrical switch whose conductance can be selectively toggled by specific environmental signals. Furthermore, we externally tuned synthetic biofilms to build nanoscale amyloid biomaterials with different structure and composition through the controlled expression of their constituent subunits with artificial gene circuits. By using synthetic cell-cell communication, our engineered biofilms can also autonomously manufacture dynamic materials whose structure and composition change with time. In addition, we show that by combining subunit-level protein engineering, controlled genetic expression of self-assembling subunit proteins, and macroscale spatial gradients, synthetic biofilms can pattern protein biomaterials across multiple length scales. This work lays a foundation for synthesizing, patterning, and controlling composite materials with engineered biological systems. We envision that this approach can be expanded to other cellular and biomaterials contexts for the construction of self-organizing, environmentally responsive, and tunable multiscale composite materials with heterogeneous functionalities.
|
10.1038/nmat3912
|
biorxiv
| 372 |
10.1101/003277
|
Filament formation by metabolic enzymes is a specific adaptation to an advanced state of cellular starvation
|
Ivana Petrovska;Elisabeth Nüske;Matthias C Munder;Gayathrie Kulasegaran;Liliana Malinovska;Sonja Kroschwald;Doris Richter;Karim Fahmy;Kimberley Gibson;Jean-Marc Verbavatz;Simon Alberti;
|
Simon Alberti
|
Max Planck Institute of Molecular Cell Biology and Genetics
|
2014-04-11
|
2
|
New Results
|
cc_by_nd
|
Cell Biology
|
https://www.biorxiv.org/content/early/2014/04/11/003277.source.xml
|
One of the key questions in biology is how the metabolism of a cell responds to changes in the environment. In budding yeast, starvation causes a drop in intracellular pH, but the functional role of this pH change is not well understood. Here, we show that the enzyme glutamine synthetase (Gln1) forms filaments at low pH and that filament formation leads to enzyme inactivation. Filament formation by Gln1 is a highly cooperative process, strongly dependent on macromolecular crowding, and involves back-to-back stacking of cylindrical homo-decamers into filaments that associate laterally to form higher order fibrils. Other metabolic enzymes also assemble into filaments at low pH. Hence, we propose that filament formation is a general mechanism to inactivate and store key metabolic enzymes during a state of advanced cellular starvation. These findings have broad implications for understanding the interplay between nutritional stress, the metabolism and the physical organization of a cell.
|
10.7554/eLife.02409
|
biorxiv
| 373 |
10.1101/003384
|
Metabolic free energy and biological codes: a ‘Data Rate Theorem’ aging model
|
Rodrick Wallace;
|
Rodrick Wallace
|
New York State Psychiatric Institute
|
2014-04-23
|
3
|
New Results
|
cc_by_nd
|
Systems Biology
|
https://www.biorxiv.org/content/early/2014/04/23/003384.source.xml
|
The living state is cognitive at every scale and level of organization. Since it is possible to associate a broad class of cognitive processes with dual information sources, many pathologies can be addressed using statistical models based on the Shannon Coding, the Shannon-McMillan Source Coding, the Rate Distortion, and the Data Rate Theorems, as these impose powerful necessary condition constraints on information generation and exchange, and on system control. Deterministic-but-for-error biological codes do not directly invoke cognition, although they may be essential subcomponents within larger cognitive processes. A formal argument, however, places such codes within a similar framework, with metabolic free energy serving as a control signal stabilizing biochemical code-and-translator dynamics in the presence of noise. Demand beyond available energy supply then expresses itself in punctuated destabilization of the coding channel, affecting a spectrum of essential biological functions. Aging, normal or prematurely driven by psychosocial or environmental stressors, must eventually interfere with the routine operation of such mechanisms, triggering chronic diseases associated with senescence. Amyloid fibril formation, intrinsically disordered protein logic gates, and cell surface glycan/lectin kelp bed logic gates are reviewed from this perspective. The results, however, generalize beyond coding systems having easily recognizable symmetry modes.
|
10.1007/s11538-014-0013-0
|
biorxiv
| 375 |
10.1101/003541
|
An optimized CRISPR/Cas toolbox for efficient germline and somatic genome engineering in Drosophila
|
Fillip Port;Hui-Min Chen;Tzumin Lee;Simon L Bullock;
|
Fillip Port
|
MRC-LMB
|
2014-03-26
|
2
|
New Results
|
cc_by_nc_nd
|
Genetics
|
https://www.biorxiv.org/content/early/2014/03/26/003541.source.xml
|
The type II CRISPR/Cas system has recently emerged as a powerful method to manipulate the genomes of various organisms. Here, we report a novel toolbox for high efficiency genome engineering of Drosophila melanogaster consisting of transgenic Cas9 lines and versatile guide RNA (gRNA) expression plasmids. Systematic evaluation reveals Cas9 lines with ubiquitous or germline restricted patterns of activity. We also demonstrate differential activity of the same gRNA expressed from different U6 snRNA promoters, with the previously untested U6:3 promoter giving the most potent effect. Choosing an appropriate combination of Cas9 and gRNA allows targeting of essential and non-essential genes with transmission rates ranging from 25% - 100%. We also provide evidence that our optimized CRISPR/Cas tools can be used for offset nicking-based mutagenesis and, in combination with oligonucleotide donors, to precisely edit the genome by homologous recombination with efficiencies that do not require the use of visible markers. Lastly, we demonstrate a novel application of CRISPR/Cas-mediated technology in revealing loss-of-function phenotypes in somatic cells following efficient biallelic targeting by Cas9 expressed in a ubiquitous or tissue-restricted manner. In summary, our CRISPR/Cas tools will facilitate the rapid evaluation of mutant phenotypes of specific genes and the precise modification of the genome with single nucleotide precision. Our results also pave the way for high throughput genetic screening with CRISPR/Cas.
|
10.1073/pnas.1405500111
|
biorxiv
| 377 |
10.1101/003566
|
Preparation of next-generation DNA sequencing libraries from ultra-low amounts of input DNA: Application to single-molecule, real-time (SMRT) sequencing on the Pacific Biosciences RS II.
|
Castle Raley;David Munroe;Kristie Jones;Yu-Chih Tsai;Yan Guo;Bao Tran;Sujatha Gowda;Jennifer L. Troyer;Daniel R. Soppet;Claudia Stewart;Robert Stephens;Jack Chen;TF Skelly;Cheryl Heiner;Jonas Korlach;Dwight Nissley;
|
Castle Raley
|
Sequencing Facility, Leidos Biomedical Research, Inc.
|
2014-03-25
|
1
|
New Results
|
cc_no
|
Genomics
|
https://www.biorxiv.org/content/early/2014/03/25/003566.source.xml
|
We have developed and validated an amplification-free method for generating DNA sequencing libraries from very low amounts of input DNA (500 picograms - 20 nanograms) for singlemolecule sequencing on the Pacific Biosciences (PacBio) RS II sequencer. The common challenge of high input requirements for single-molecule sequencing is overcome by using a carrier DNA in conjunction with optimized sequencing preparation conditions and re-use of the MagBead-bound complex. Here we describe how this method can be used to produce sequencing yields comparable to those generated from standard input amounts, but by using 1000-fold less starting material.
|
NA
|
biorxiv
| 378 |
10.1101/003533
|
Rice BiP3 regulates immunity mediated by the PRRs XA3 and XA21 but not immunity mediated by the NB-LRR protein, Pi5
|
Chang-Jin Park;Min-Young Song;Chi-Yeol Kim;Jong-Seong Jeon;Pamela C. Ronald;
|
Pamela C. Ronald
|
Department of Plant Pathology and the Genome Center, University of California Davis
|
2014-03-26
|
1
|
Confirmatory Results
|
cc_no
|
Plant Biology
|
https://www.biorxiv.org/content/early/2014/03/26/003533.source.xml
|
Plant innate immunity is mediated by pattern recognition receptors (PRRs) and intracellular NB-LRR (nucleotide-binding domain and leucine-rich repeat) proteins. Overexpression of the endoplasmic reticulum (ER) chaperone, luminal-binding protein 3 (BiP3) compromises resistance to Xanthomonas oryzae pv. oryzae (Xoo) mediated by the rice PRR XA21 (Park et al., PLoS ONE 5(2): e9262). Here we show that BiP3 overexpression also compromises resistance mediated by rice XA3, a PRR that provides broad-spectrum resistance to Xoo. In contrast, BiP3 overexpression has no effect on resistance mediated by rice Pi5, an NB-LRR protein that confers resistance to the fungal pathogen Magnaporthe oryzae (M. oryzae). Our results suggest that rice BiP3 regulates membrane-resident PRR-mediated immunity.
|
10.1016/j.bbrc.2014.04.093
|
biorxiv
| 379 |
10.1101/003558
|
How many digits in a mean are worth reporting?
|
R.S. Clymo;
|
R.S. Clymo
|
Queen Mary University of London
|
2014-03-25
|
1
|
New Results
|
cc_by
|
Scientific Communication and Education
|
https://www.biorxiv.org/content/early/2014/03/25/003558.source.xml
|
Most bioscientists need to report mean values, yet many have little idea of how many digits are significant, and at what point further digits are mere random junk. Thus a recent report that the mean of 17 values was 3.863 with a standard error of the mean (SEM) of 2.162 revealed only that none of the seven authors understood the limitations of their work. The simple rule derived here by experiment for restricting a mean value to its significant digits (sig-digs) is this: the last sig-dig in the mean value is at the same decimal decade as the first sig-dig (the first non-zero) in the SEM. An extended rule for the mean, and a different rule for the SEM itself are also derived. For the example above the reported values should be a mean of 4 with SEM 2.2. Routine application of these simple rules will often show that a result is not as compelling as one had hoped.
|
NA
|
biorxiv
| 380 |
10.1101/003608
|
A Comparison of Peak Callers Used for DNase-seq Data
|
Hashem Koohy;Thomas Down;Mikhail Spivakov;Tim Hubbard;
|
Hashem Koohy
|
Babraham Institute
|
2014-04-14
|
3
|
New Results
|
cc_by_nc_nd
|
Bioinformatics
|
https://www.biorxiv.org/content/early/2014/04/14/003608.source.xml
|
Genome-wide profiling of open chromatin regions using DNase I and high-throughput sequencing (DNase-seq) is an increasingly popular approach for finding and studying regulatory elements. A variety of algorithms have been developed to identify regions of open chromatin from raw sequence-tag data, which has motivated us to assess and compare their performance.\n\nIn this study, four published, publicly available peak calling algorithms used for DNase-seq data analysis (F-seq, Hotspot, MACS and ZINBA) are assessed at a range of signal thresholds on two published DNase-seq datasets for three cell types. The results were benchmarked against an independent dataset of regulatory regions derived from ENCODE in vivo transcription factor binding data for each particular cell type. The level of overlap between peak regions reported by each algorithm and this ENCODE-derived reference set was used to assess sensitivity and specificity of the algorithms.\n\nOur study suggests that F-seq has a slightly higher sensitivity than the next best algorithms. Hotspot and the ChIP-seq oriented method, MACS, both perform competitively when used with their default parameters. However the generic peak finder ZINBA appears to be less sensitive than the other three.\n\nWe also assess accuracy of each algorithm over a range of signal thresholds. In particular, we show that the accuracy of F-Seq can be considerably improved by using a threshold setting that is different from the default value.
|
10.1371/journal.pone.0096303
|
biorxiv
| 383 |
10.1101/003616
|
The HVCN1 channel conducts protons into the phagocytic vacuole of neutrophils to produce a physiologically alkaline pH
|
Adam P Levine;Michael R Duchen;Anthony W Segal;
|
Anthony W Segal
|
Division of Medicine, University College London
|
2014-03-27
|
1
|
New Results
|
cc_no
|
Cell Biology
|
https://www.biorxiv.org/content/early/2014/03/27/003616.source.xml
|
Activation of the NADPH oxidase (NOX2) of the phagocytic vacuole of neutrophils is essential for innate immunity. Sustained activity of the oxidase requires that charge movements across the membrane are balanced. A role for the proton channel, HVCN1, has been proposed but not proven. Using the ratiometric pH indicator SNARF, introduced into the cytosol and separately into the vacuole coupled to Candida, we used confocal microscopy to measure changes in pH in these two compartments in human and mouse neutrophils. Shortly after phagocytosis by human cells, the vacuolar pH rose to ~9, at which it was maintained for ~20 minutes, while the cytosol showed a small acidification of ~0.25 pH unit. Alkalinisation has important consequences for the microbicidal and digestive functions of vacuolar enzymes. In HVCN1 knock out mouse neutrophils, the phagocytosis induced respiratory burst was halved to ~3 fmols per Candida, the vacuolar pH rose to >11 and the cytosol acidified excessively to pH ~6.75. These changes were prevented by the protonophore CCCP. The rate of extrusion of protons into the extracellular medium following phagocytosis was not significantly different from wild type neutrophils suggesting that cytoplasmic acidification resulted from the loss of the proton sink into the vacuole. HVCN1 phagocytic vacuoles showed considerable swelling, and this was blocked by CCCP and decreased by valinomycin. Stoichiometric considerations indicated that the HVCN1 channel compensates 90-95% of the oxidase-induced charge in normal cells, and in its absence, charge is carried by ions other than protons, including K+.
|
10.1371/journal.pone.0125906
|
biorxiv
| 384 |
10.1101/003574
|
3D mapping of disease in ant societies reveals a strategy of a specialized parasite
|
Raquel G Loreto;Simon L Elliot;Mayara LR Freitas;Thairine M Pereira;David P Hughes;
|
Raquel G Loreto
|
Pennsylvania State University & Federal University of Vi?osa
|
2014-03-27
|
1
|
New Results
|
cc_no
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/03/27/003574.source.xml
|
Despite the widely held position that the social insects have evolved effective ways to limit infectious disease spread, many pathogens and parasites do attack insect societies. Maintaining a disease-free nest environment is an important evolutionary feature, but since workers have to leave the nest to forage they are routinely exposed to disease. Here we show that despite effective social immunity, in which workers act collectively to reduce disease inside the nest, 100% of studied ant colonies of Camponotus rufipes in a Brazilian Rainforest were infected by the specialized fungal parasite Ophiocordyceps unilateralis s.l. Not only is disease present for all colonies but long-term dynamics over 20 months revealed disease is a permanent feature. Using 3D maps, we showed the parasite optimizes its transmission by controlling workers behavior to die on the doorstep of the colony, where susceptible foragers are predictable in time and space. Therefore, despite social immunity, specialized diseases of ants have evolved effective strategies to exploit insect societies.
|
10.1371/journal.pone.0103516
|
biorxiv
| 385 |
10.1101/003640
|
The Scramble Conversion Tool
|
James K Bonfield;
|
James K Bonfield
|
Wellcome Trust Sanger Institute
|
2014-03-28
|
1
|
New Results
|
cc_by
|
Bioinformatics
|
https://www.biorxiv.org/content/early/2014/03/28/003640.source.xml
|
MotivationThe reference CRAM file format implementation is in Java. We present \"Scramble\": a new C implementation of SAM, BAM and CRAM file I/O.\n\nResultsThe C API for CRAM is 1.5-1.7x slower than BAM at decoding, but 1.8-2.6x faster at encoding. We see file size savings of 40-50%.\n\nAvailabilitySource code is available from http://sourceforge.net/projects/staden/files/io_lib/
|
10.1093/bioinformatics/btu390
|
biorxiv
| 386 |
10.1101/003624
|
Numerous new mitogenomic sequences and multiple new environmental DNA markers for invasive bighead and silver carp (Hypophthalmichthys nobilis and H. molitrix) populations in North America
|
Richard F. Lance;Heather L. Farrington;Christine E. Edwards;Xin Guan;Matthew R. Carr;Kelly Baerwaldt;
|
Richard F. Lance
|
US Army ERDC Environmental Laboratory
|
2014-03-30
|
1
|
New Results
|
cc_by_nd
|
Ecology
|
https://www.biorxiv.org/content/early/2014/03/30/003624.source.xml
|
Invasive Asian bighead and silver carp (Hypophthalmichthys nobilis and H. molitrix) pose a substantial threat to North American waterways. Recently, environmental DNA (eDNA), the use of species-specific genetic assays to detect the DNA of a particular species in a water sample, has gained recognition as a tool for tracking the invasion front of these species toward the Great Lakes. The goal of this study was to develop new species-specific conventional PCR (cPCR) and quantitative (qPCR) markers for detection of these species in North American waterways. We first generated complete mitochondrial genome sequences from 33 bighead and 29 silver carp individuals collected throughout their introduced range. These sequences were aligned with other common and closely related species to identify potential eDNA markers. We then field-tested these genetic markers for species-specificity and sensitivity in environmental samples. Newly developed markers performed well in field trials, had low false positive rates and had comparable sensitivity compared to current markers. The new markers developed in this study greatly expand the number of species-specific genetic markers available to track the invasion front of bighead and silver carp, and can be used to improve the resolution of these assays. Additionally, the use of the qPCR markers developed in this study may reduce sample processing time and cost of eDNA monitoring for these species.
|
10.1371/journal.pone.0117803
|
biorxiv
| 389 |
10.1101/003673
|
Geometry shapes evolution of early multicellularity
|
Eric Libby;Will Ratcliff;Mike Travisano;Ben Kerr;
|
Eric Libby
|
Santa Fe Institute
|
2014-03-30
|
1
|
New Results
|
cc_no
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/03/30/003673.source.xml
|
Organisms have increased in complexity through a series of major evolutionary transitions, in which formerly autonomous entities become parts of a novel higher-level entity. One intriguing feature of the higher-level entity after some major transitions is a division of reproductive labor among its lower-level units. Although it can have clear benefits once established, it is unknown how such reproductive division of labor originates. We consider a recent evolution experiment on the yeast Saccharomyces cerevisiae as a unique platform to address the issue of reproductive differentiation during an evolutionary transition in individuality. In the experiment, independent yeast lineages evolved a multicellular \"snowflake-like\" cluster form in response to gravity selection. Shortly after the evolution of clusters, the yeast evolved higher rates of cell death. While cell death enables clusters to split apart and form new groups, it also reduces their performance in the face of gravity selection. To understand the selective value of increased cell death, we create a mathematical model of the cellular arrangement within snowflake yeast clusters. The model reveals that the mechanism of cell death and the geometry of the snowflake interact in complex, evolutionarily important ways. We find that the organization of snowflake yeast imposes powerful limitations on the available space for new cell growth. By dying more frequently, cells in clusters avoid encountering space limitations, and, paradoxically, reach higher numbers. In addition, selection for particular group sizes can explain the increased rate of apoptosis both in terms of total cell number and total numbers of collectives. Thus, by considering the geometry of a primitive multicellular organism we can gain insight into the initial emergence of reproductive division of labor during an evolutionary transition in individuality.
|
10.1371/journal.pcbi.1003803
|
biorxiv
| 390 |
10.1101/003707
|
An evolutionary resolution of manipulation conflict
|
Mauricio González-Forero;
|
Mauricio Gonzélez-Forero
|
University of Tennessee, Knoxville, and National Institute for Mathematical and Biological Synthesis
|
2014-04-14
|
3
|
New Results
|
cc_by_nc_nd
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/04/14/003707.source.xml
|
Individuals can manipulate the behavior of social partners. However, manipulation may conflict with the fitness interests of the manipulated individuals. Manipulated individuals can then be favored to resist manipulation, possibly reducing or eliminating the manipulated behavior in the long run. I use a mathematical model to show that conflicts where manipulation and resistance coevolve can disappear as a result of the coevolutionary process. I find that while manipulated individuals are selected to resist, they can simultaneously be favored to express the manipulated behavior at higher efficiency (i.e., providing increasing fitness effects to recipients of the manipulated behavior). Efficiency can increase to a point at which selection for resistance disappears. This process yields an efficient social behavior that is induced by social partners, and over which the inducing and induced individuals are no longer in conflict. A necessary factor is costly inefficiency. I develop the model to address the evolution of advanced eusociality via maternal manipulation (AEMM). The model predicts AEMM to be particularly likely in taxa with ancestrally imperfect resistance to maternal manipulation. Costly inefficiency occurs if the cost of delayed dispersal is larger than the benefit of exploiting the maternal patch. I discuss broader implications of the process.
|
10.1111/evo.12420
|
biorxiv
| 393 |
10.1101/003764
|
New whole genome de novo assemblies of three divergent strains of rice (O. sativa) documents novel gene space of aus and indica
|
Michael C Schatz;Lyza G Maron;Joshua C Stein;Alejandro Hernandez Wences;James Gurtowski;Eric Biggers;Hayan Lee;Melissa Kramer;Eric Antonio;Elena Ghiban;Mark H Wright;Jer-ming Chia;Doreen Ware;Susan R McCouch;William Richard McCombie;
|
William Richard McCombie
|
Cold Spring Harbor Laboratory
|
2014-04-02
|
1
|
New Results
|
cc_by_nc
|
Genomics
|
https://www.biorxiv.org/content/early/2014/04/02/003764.source.xml
|
The use of high throughput genome-sequencing technologies has uncovered a large extent of structural variation in eukaryotic genomes that makes important contributions to genomic diversity and phenotypic variation. Currently, when the genomes of different strains of a given organism are compared, whole genome resequencing data are aligned to an established reference sequence. However when the reference differs in significant structural ways from the individuals under study, the analysis is often incomplete or inaccurate. Here, we use rice as a model to explore the extent of structural variation among strains adapted to different ecologies and geographies, and show that this variation can be significant, often matching or exceeding the variation present in closely related human populations or other mammals. We demonstrate how improvements in sequencing and assembly technology allow rapid and inexpensive de novo assembly of next generation sequence data into high-quality assemblies that can be directly compared to provide an unbiased assessment. Using this approach, we are able to accurately assess the \"pan-genome\" of three divergent rice varieties and document several megabases of each genome absent in the other two. Many of the genome-specific loci are annotated to contain genes, reflecting the potential for new biological properties that would be missed by standard resequencing approaches. We further provide a detailed analysis of several loci associated with agriculturally important traits, illustrating the utility of our approach for biological discovery. All of the data and software are openly available to support further breeding and functional studies of rice and other species.
|
10.1186/s13059-014-0506-z
|
biorxiv
| 394 |
10.1101/003731
|
HGTector: An automated method facilitating genome-wide discovery of putative horizontal gene transfers
|
Qiyun Zhu;Michael Kosoy;Katharina Dittmar;
|
Katharina Dittmar
|
University at Buffalo, State University of New York
|
2014-04-02
|
1
|
New Results
|
cc_by_nc_nd
|
Bioinformatics
|
https://www.biorxiv.org/content/early/2014/04/02/003731.source.xml
|
A new computational method of rapid, exhaustive and genome-wide detection of HGT was developed, featuring the systematic analysis of BLAST hit distribution patterns in the context of a priori defined hierarchical evolutionary categories. Genes that fall beyond a series of statistically determined thresholds are identified as not adhering to the typical vertical history of the organisms in question, but instead having a putative horizontal origin. Tests on simulated genomic data suggest that this approach effectively targets atypically distributed genes that are highly likely to be HGT-derived, and exhibits robust performance compared to conventional BLAST-based approaches. This method was further tested on real genomic datasets, including Rickettsia genomes, and was compared to previous studies. Results show consistency with currently employed categories of HGT prediction methods. In-depth analysis of both simulated and real genomic data suggests that the method is notably insensitive to stochastic events such as gene loss, rate variation and database error, which are common challenges to the current methodology. An automated pipeline was created to implement this approach and was made publicly available at: https://github.com/DittmarLab/HGTector. The program is versatile, easily deployed, has low requirements for computational resources, and is an effective tool for initial or standalone large-scale discovery of candidate HGT-derived genes.
|
10.1186/1471-2164-15-717
|
biorxiv
| 395 |
10.1101/003772
|
Comparison of the theoretical and real-world evolutionary potential of a genetic circuit.
|
Manuel Razo-Mejia;James Boedicker;Daniel Jones;Alexander de Luna;Justin Block Kinney;Rob Phillips;
|
Rob Phillips
|
California Institute of Technology
|
2014-04-02
|
1
|
New Results
|
cc_by_nc_nd
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/04/02/003772.source.xml
|
With the development of next-generation sequencing technologies, many large scale experimental efforts aim to map genotypic variability among individuals. This natural variability in populations fuels many fundamental biological processes, ranging from evolutionary adaptation and speciation to the spread of genetic diseases and drug resistance. An interesting and important component of this variability is present within the regulatory regions of genes. As these regions evolve, accumulated mutations lead to modulation of gene expression, which may have consequences for the phenotype. A simple model system where the link between genetic variability, gene regulation and function can be studied in detail is missing. In this article we develop a model to explore how the sequence of the wild-type lac promoter dictates the fold change in gene expression. The model combines single-base pair resolution maps of transcription factor and RNA polymerase binding energies with a comprehensive thermodynamic model of gene regulation. The model was validated by predicting and then measuring the variability of lac operon regulation in a collection of natural isolates. We then implement the model to analyze the sensitivity of the promoter sequence to the regulatory output, and predict the potential for regulation to evolve due to point mutations in the promoter region.
|
10.1088/1478-3975/11/2/026005
|
biorxiv
| 396 |
10.1101/003749
|
Multilocus Species Trees Show the Recent Adaptive Radiation of the Mimetic Heliconius Butterflies
|
Krzysztof M Kozak;Niklas Wahlberg;Andrew Neild;Kanchon K Dasmahapatra;James Mallet;Chris D Jiggins;
|
Krzysztof M Kozak
|
Department of Zoology, University of Cambridge
|
2014-04-02
|
1
|
New Results
|
cc_by_nc_nd
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/04/02/003749.source.xml
|
Mullerian mimicry among Neotropical Heliconiini butterflies is an excellent example of natural selection, and is associated with the diversification of a large continental-scale radiation. Some of the processes driving the evolution of mimicry rings are likely to generate incongruent phylogenetic signals across the assemblage, and thus pose a challenge for systematics. We use a dataset of 22 mitochondrial and nuclear markers from 92% of species in the tribe to re-examine the phylogeny of Heliconiini with both supermatrix and multi-species coalescent approaches, characterise the patterns of conflicting signal and compare the performance of various methodological approaches to reflect the heterogeneity across the data. Despite the large extent of reticulate signal and strong conflict between markers, nearly identical topologies are consistently recovered by most of the analyses, although the supermatrix approach fails to reflect the underlying variation in the history of individual loci. The first comprehensive, time-calibrated phylogeny of this group is used to test the hypotheses of a diversification rate increase driven by the dramatic environmental changes in the Amazonia over the past 23 million years, or changes caused by diversity-dependent effects on the rate of diversification. We find that the tribe Heliconiini had doubled its rate of speciation around 11 Ma and that the presently most speciose genus Heliconius started diversifying rapidly at 10 Ma, likely in response to the recent drastic changes in topography of the region. Our study provides comprehensive evidence for a rapid adaptive radiation among an important insect radiation in the most biodiverse region of the planet.
|
10.1093/sysbio/syv007
|
biorxiv
| 397 |
10.1101/003913
|
MicroRNAs Regulate the Wnt/Ca2+ Signaling Pathway to Promote the Secretion of Insulin in Pancreatic Nestin-Positive Progenitor Cells
|
Chunyu Bai;Xiangchen Li;Yuhua Gao;Taofeng Lu;Kunfu Wang;Qian Li;Hui Xiong;Jia Chen;Ping Zhang;Wenjie Wang;Tingting Sun;Zhiqiang Shan;Bo Sun;Pei Pei;Changqing Liu;Weijun Guan;Yuehui Ma;
|
Yuehui Ma
|
Beijing animal sciences institution
|
2014-04-04
|
1
|
New Results
|
cc_no
|
Cell Biology
|
https://www.biorxiv.org/content/early/2014/04/04/003913.source.xml
|
MicroRNAs (miRNAs) are small noncoding RNAs that bind to the 3'-UTR of mRNAs and function mainly in post-transcriptional regulation. MiRNAs have been implicated to play roles in organ development, including that of the pancreas. Many miRNAs, such as miR-375, miR-124, miR-7, miR-21 and miR-221, have been shown to regulate insulin production as well as insulin secretion. However, it is not known whether miRNAs can regulate insulin secretion via the control of intracellular Ca2+ in pancreatic beta cells. In this research, expression profiles of miRNAs and mRNAs were investigated using RNA-sequencing and microarray analysis in chicken pancreatic nestin-positive progenitor cells and differentiated pancreatic beta cells. A number of miRNAs were up-regulated after differentiation of progenitors into beta cells, which regulate cell signaling pathways to control cell function. miR-223 and miR146a were shown to promote insulin secretion from pancreatic beta cells by regulating the concentration of intracellular Ca2+ via the down-regulation of their target genes.
|
NA
|
biorxiv
| 403 |
10.1101/003756
|
Diversity of entomopathogens Fungi: Which groups conquered the insect body?
|
João P.M. Araújo;David P Hughes;
|
Jo?o P.M. Ara?jo
|
Pennsylvania State University
|
2014-04-14
|
2
|
New Results
|
cc_by_nc
|
Ecology
|
https://www.biorxiv.org/content/early/2014/04/14/003756.source.xml
|
The entomopathogenic Fungi comprise a wide range of ecologically diverse species. This group of parasites can be found distributed among all fungal phyla and as well as among the ecologically similar but phylogenetically distinct Oomycetes or water molds, that belong to a different kingdom (Stramenopila). As a group, the entomopathogenic fungi and water molds parasitize a wide range of insect hosts from aquatic larvae in streams to adult insects of high canopy tropical forests. Their hosts are spread among 18 orders of insects, in all developmental stages such as: eggs, larvae, pupae, nymphs and adults exhibiting completely different ecologies. Such assortment of niches has resulted in these parasites evolving a considerable morphological diversity, resulting in enormous biodiversity, much of which remains unknown. Here we gather together a huge amount of records of these entomopathogens to comparing and describe both their morphologies and ecological traits. These findings highlight a wide range of adaptations that evolved following the evolutionary transition to infecting the most diverse and widespread animals on Earth, the insects.
|
NA
|
biorxiv
| 405 |
10.1101/003897
|
Intermediate Migration Yields Optimal Adaptation in Structured, Asexual Populations
|
Arthur Covert III;Claus O Wilke;
|
Arthur Covert III
|
University of Texas at Austin
|
2014-04-04
|
1
|
New Results
|
cc_by_nc_nd
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/04/04/003897.source.xml
|
Most evolving populations are subdivided into multiple subpopulations connected to each other by varying levels of gene flow. However, how population structure and gene flow (i.e., migration) affect adaptive evolution is not well understood. Here, we studied the impact of migration on asexually reproducing evolving computer programs (digital organisms). We found that digital organisms evolve the highest fitness values at intermediate migration rates, and we tested three hypotheses that could potentially explain this observation: (i) migration promotes passage through fitness valleys, (ii) migration increases genetic variation, and (iii) migration reduces clonal interference through a process called leapfrogging. We found that migration had no appreciable effect on the number of fitness valleys crossed and that genetic variation declined monotonously with increasing migration rates, instead of peaking at the optimal migration rate. However, the number of leapfrogging events, in which a superior beneficial mutation emerges on a genetic background that predates the previously best genotype in the population, did peak at the optimal migration rate. We thus conclude that in structured, asexual populations intermediate migration rates allow for optimal exploration of multiple, distinct fitness peaks, and thus yield the highest long-term adaptive success.
|
NA
|
biorxiv
| 406 |
10.1101/003954
|
SplitMEM: Graphical pan-genome analysis with suffix skips
|
Shoshana Marcus;Hayan Lee;Michael Schatz;
|
Michael Schatz
|
Cold Spring Harbor Laboratory
|
2014-04-06
|
1
|
New Results
|
cc_by_nc_nd
|
Bioinformatics
|
https://www.biorxiv.org/content/early/2014/04/06/003954.source.xml
|
Motivation: With the rise of improved sequencing technologies, genomics is expanding from a single reference per species paradigm into a more comprehensive pan-genome approach with multiple individuals represented and analyzed together. One of the most sophisticated data structures for representing an entire population of genomes is a compressed de Bruijn graph. The graph structure can robustly represent simple SNPs to complex structural variations far beyond what can be done from linear sequences alone. As such there is a strong need to develop algorithms that can efficiently construct and analyze these graphs. Results: In this paper we explore the deep topological relationships between the suffix tree and the compressed de Bruijn graph. We introduce a novel O(n log n) time and space algorithm called splitMEM, that directly constructs the compressed de Bruijn graph for a pan-genome of total length n. To achieve this time complexity, we augment the suffix tree with suffix skips, a new construct that allows us to traverse several suffix links in constant time, and use them to efficiently decompose maximal exact matches (MEMs) into the graph nodes. We demonstrate the utility of splitMEM by analyzing the pan- genomes of 9 strains of Bacillus anthracis and 9 strains of Escherichia coli to reveal the properties of their core genomes. Availability: The source code and documentation are available open- source at http://splitmem.sourceforge.net
|
10.1093/bioinformatics/btu756
|
biorxiv
| 407 |
10.1101/003939
|
Evolutionary Multiplayer Games
|
Chaitanya S Gokhale;Arne Traulsen;
|
Arne Traulsen
|
Max Planck Institute for Evolutionary Biology
|
2014-04-15
|
2
|
Confirmatory Results
|
cc_by
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/04/15/003939.source.xml
|
Evolutionary game theory has become one of the most diverse and far reaching theories in biology. Applications of this theory range from cell dynamics to social evolution. However, many applications make it clear that inherent non-linearities of natural systems need to be taken into account. One way of introducing such non-linearities into evolutionary games is by the inclusion of multiple players. An example is of social dilemmas, where group benefits could e.g. increase less than linear with the number of cooperators. Such multiplayer games can be introduced in all the fields where evolutionary game theory is already well established. However, the inclusion of non-linearities can help to advance the analysis of systems which are known to be complex, e.g. in the case of non-Mendelian inheritance. We review the diachronic theory and applications of multiplayer evolutionary games and present the current state of the field. Our aim is a summary of the theoretical results from well-mixed populations in infinite as well as finite populations. We also discuss examples from three fields where the theory has been successfully applied, ecology, social sciences and population genetics. In closing, we probe certain future directions which can be explored using the complexity of multiplayer games while preserving the promise of simplicity of evolutionary games.
|
10.1007/s13235-014-0106-2
|
biorxiv
| 409 |
10.1101/003962
|
KmerStream: Streaming algorithms for k-mer abundance estimation
|
Páll Melsted;Bjarni V. Halldórsson;
|
Péll Melsted
|
University of Iceland
|
2014-04-07
|
2
|
New Results
|
cc_by
|
Bioinformatics
|
https://www.biorxiv.org/content/early/2014/04/07/003962.source.xml
|
Motivation: Several applications in bioinformatics, such as genome assemblers and error corrections methods, rely on counting and keeping track of k-mers (substrings of length k). Histograms of k-mer frequencies can give valuable insight into the underlying distribution and indicate the error rate and genome size sampled in the sequencing experiment.\n\nResults: We present KmerStream, a streaming algorithm for computing statistics for high throughput sequencing data based on the frequency of k-mers. The algorithm runs in time linear in the size of the input and the space requirement are logarithmic in the size of the input. This very low space requirement allows us to deal with much larger datasets than previously presented algorithms. We derive a simple model that allows us to estimate the error rate of the sequencing experiment, as well as the genome size, using only the aggregate statistics reported by KmerStream and validate the accuracy on sequences from a PhiX control.\n\nAs an application we show how KmerStream can be used to compute the error rate of a DNA sequencing experiment. We run KmerStream on a set of 2656 whole genome sequenced individuals and compare the error rate to quality values reported by the sequencing equipment. We discover that while the quality values alone are largely reliable as a predictor of error rate, there is considerable variability in the error rates between sequencing runs, even when accounting for reported quality values.\n\nAvailability: The tool KmerStream is written in C++ and is released under a GPL license. It is freely available at https://github.com/pmelsted/KmerStream\n\nContact: [email protected]
|
10.1093/bioinformatics/btu713
|
biorxiv
| 411 |
10.1101/004028
|
A signature of power law network dynamics
|
Ashish Bhan;Animesh Ray;
|
Animesh Ray
|
Keck Graduate Institute
|
2014-04-09
|
1
|
New Results
|
cc_by_nc_nd
|
Bioinformatics
|
https://www.biorxiv.org/content/early/2014/04/09/004028.source.xml
|
Can one hear the sound of a growing network? We address the problem of recognizing the topology of evolving biological or social networks. Starting from percolation theory, we analytically prove a linear inverse relationship between two simple graph parameters--the logarithm of the average cluster size and logarithm of the ratio of the edges of the graph to the theoretically maximum number of edges for that graph--that holds for all growing power law graphs. The result establishes a novel property of evolving power-law networks in the asymptotic limit of network size. Numerical simulations as well as fitting to real-world citation co-authorship networks demonstrate that the result holds for networks of finite sizes, and provides a convenient measure of the extent to which an evolving family of networks belongs to the same power-law class.
|
NA
|
biorxiv
| 418 |
10.1101/003947
|
Building realistic assemblages with a Joint Species Distribution Model
|
David J. Harris;
|
David J. Harris
|
UC Davis
|
2014-04-09
|
1
|
New Results
|
cc_by
|
Ecology
|
https://www.biorxiv.org/content/early/2014/04/09/003947.source.xml
|
O_LISpecies distribution models (SDMs) can be used to predict how individual species--and whole assemblages of species--will respond to a changing environment. Until now, these models have either assumed (1) that species occurrence probabilities are uncorrelated, or (2) that species respond linearly to preselected environmental variables. These two assumptions currently prevent ecologists from modeling assemblages with realistic co-occurrence and species richness properties.\nC_LIO_LIThis paper introduces a stochastic feedforward neural network, called mistnet, which makes neither assumption. Thus, unlike most SDMs, mistnet can account for non-independent co-occurrence patterns driven by unobserved environmental heterogeneity. And unlike recently proposed Joint SDMs, mistnet can also learn nonlinear functions relating species occurrence probabilities to environmental predictors.\nC_LIO_LIMistnet makes more accurate predictions about the North American bird communities found along Breeding Bird Survey transects than several alternative methods tested. In particular, typical assemblages held out of sample for validation were nearly 50,000 times more likely under the mistnet model than under independent combinations of single-species models.\nC_LIO_LIApart from improved accuracy, mistnet shows two other important benefits for ecological research and management. First: by analyzing co-occurrence data, mistnet can identify unmeasured--and perhaps unanticipated--environmental variables that drive species turnover. For example, mistnet identified a strong grassland/forest gradient, even though only temperature and precipitation were given as model inputs. Second: mistnet is able to take advantage of incomplete data sets to guide its predictions towards more realistic assemblages. For example, mistnet automatically adjusts its expectations to include more forest-associated species in response to a stray observation of a forest-dwelling warbler.\nC_LI
|
NA
|
biorxiv
| 419 |
10.1101/004101
|
Whole Genome Bisulfite Sequencing of Cell Free DNA and its Cellular Contributors Uncovers Placenta Hypomethylated Domains
|
Taylor Jensen;Sung K Kim;Zhanyang Zhu;Christine Chin;Claudia Gebhard;Tim Lu;Cosmin Deciu;Dirk van den Boom;Mathias Ehrich;
|
Taylor Jensen
|
Sequenom Laboratories
|
2014-04-11
|
1
|
New Results
|
cc_no
|
Genomics
|
https://www.biorxiv.org/content/early/2014/04/11/004101.source.xml
|
BackgroundCirculating cell free fetal DNA has enabled non-invasive prenatal fetal aneuploidy testing without direct discrimination of the genetically distinct maternal and fetal DNA. Current testing may be improved by specifically enriching the sample material for fetal DNA. DNA methylation may allow for such a separation of DNA and thus support additional clinical opportunities; however, this depends on knowledge of the methylomes of ccf DNA and its cellular contributors.\n\nResultsWhole genome bisulfite sequencing was performed on a set of unmatched samples including ccf DNA from 8 non-pregnant (NP) and 7 pregnant female donors and genomic DNA from 7 maternal buffy coat and 5 placenta samples. We found CpG cytosines within longer fragments were more likely to be methylated, linking DNA methylation and fragment size in ccf DNA. Comparison of the methylomes of placenta and NP ccf DNA revealed many of the 51,259 identified differentially methylated regions (DMRs) were located in domains exhibiting consistent placenta hypomethylation across millions of consecutive bases, regions we termed placenta hypomethylated domains (PHDs). We found PHDs were consistently located within regions exhibiting low CpG and gene density. DMRs identified when comparing placenta to NP ccf DNA were recapitulated in pregnant ccf DNA, confirming the ability to detect differential methylation in ccf DNA mixtures.\n\nConclusionsWe generated methylome maps for four sample types at single base resolution, identified a link between DNA methylation and fragment length in ccf DNA, identified DMRs between sample groups, and uncovered the presence of megabase-size placenta hypomethylated domains. Furthermore, we anticipate these results to provide a foundation to which future studies using discriminatory DNA methylation may be compared.
|
10.1186/s13059-015-0645-x
|
biorxiv
| 423 |
10.1101/004168
|
Neural lineage induction reveals multi-scale dynamics of 3D chromatin organization
|
Aleksandra Pekowska;Bernd Klaus;Felix Alexander Klein;Simon Anders;Malgorzata Oles;Lars Michael Steinmetz;Paul Bertone;Wolfgang Huber;
|
Aleksandra Pekowska
|
European Molecular Biology Laboratory (EMBL)
|
2014-04-11
|
1
|
New Results
|
cc_by_nc_nd
|
Molecular Biology
|
https://www.biorxiv.org/content/early/2014/04/11/004168.source.xml
|
Regulation of gene expression underlies cell identity. Chromatin structure and gene activity are linked at multiple levels, via positioning of genomic loci to transcriptionally permissive or repressive environments and by connecting cis-regulatory elements such as promoters and enhancers. However, the genome-wide dynamics of these processes during cell differentiation has not been characterized. Using tethered chromatin conformation capture (TCC) sequencing we determined global three-dimensional chromatin structures in mouse embryonic stem (ES) and neural stem (NS) cell derivatives. We found that changes in the propensity of genomic regions to form inter-chromosomal contacts are pervasive in neural induction and are associated with the regulation of gene expression. Moreover, we found a pronounced contribution of euchromatic domains to the intra-chromosomal interaction network of pluripotent cells, indicating the existence of an ES cell-specific mode of chromatin organization. Mapping of promoter-enhancer interactions in pluripotent and differentiated cells revealed that spatial proximity without enhancer element activity is a common architectural feature in cells undergoing early developmental changes. Activity-independent formation of higher-order contacts between cis-regulatory elements, predominant at complex loci, may thus provide an additional layer of transcriptional control.
|
NA
|
biorxiv
| 425 |
10.1101/004135
|
Direct Reciprocity Under Uncertainty Does Not Explain One-shot Cooperation, but Demonstrates the Benefits of a Norm Psychology
|
Matthew Zefferman;
|
Matthew Zefferman
|
National Institute for Mathematical and Biological Synthesis, University of Tennessee
|
2014-04-11
|
1
|
New Results
|
cc_by_nc_nd
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/04/11/004135.source.xml
|
Humans in many societies cooperate in economic experiments at much higher levels than would be expected if their goal was maximizing economic returns, even when their interactions are anonymous and one-shot. This is a puzzle because paying a cost to benefit another in one-shot interactions gives no direct or indirect benefits to the cooperator. This paper explores the logic of two competing evolutionary hypotheses to explain this behavior. The \"norm psychology\" hypothesis holds that a player's choice of strategy reflects socially-learned cultural norms. Its premise is that over the course of human evolutionary history, cultural norms varied considerably across human societies and through a process of gene-culture co-evolution, humans evolved mechanisms to learn and adopt the norms that are successful in their particular society. The \"mismatch\" hypothesis holds that pro-social preferences evolved genetically in our hunter-gatherer past where one-shot anonymous interactions were rare and these preferences are misapplied in modern laboratory settings. I compare these hypotheses by adopting a well-known model of the mismatch hypothesis and show that selection for one-shot cooperation in the model is an artifact of agents being constrained to only two strategies: Tit-for-Tat and Always Defect. Allowing for repentant and forgiving strategies reverses selection away from one-shot cooperation under all environmental parameters. Direct reciprocity does not necessarily lead to cooperation, but instead generates many different normative equilibria depending on a groups idiosyncratic evolutionary history. Therefore, an agent whose behavior is evoked solely from non-cultural environmental cues will be disadvantaged relative to an agent who learns the locally successful norms. Cooperation in one-shot laboratory experiments is thus more easily explained as the result of a psychology evolved for learning social norms than as a genetic mismatch.
|
10.1016/j.evolhumbehav.2014.04.003
|
biorxiv
| 426 |
10.1101/004127
|
Average oxidation state of carbon in proteins
|
Jeffrey M. Dick;
|
Jeffrey M. Dick
|
Curtin University
|
2014-04-14
|
1
|
New Results
|
cc_by
|
Biochemistry
|
https://www.biorxiv.org/content/early/2014/04/14/004127.source.xml
|
The degree of oxidation of carbon atoms in organic molecules depends on the covalent structure. In proteins, the average oxidation state of carbon (ZC) can be calculated as an elemental ratio from the chemical formula. To investigate oxidation-reduction (redox) patterns, groups of proteins from different subcellular locations and phylogenetic divisions were selected for comparison. Extracellular proteins of yeast have a relatively high oxidation state of carbon, corresponding with oxidizing conditions outside of the cell. However, an inverse relationship between ZC and redox potential occurs between the endoplasmic reticulum and cytoplasm; this trend is interpreted as resulting from overall coupling of protein turnover to the formation of a lower glutathione redox potential in the cytoplasm. In Rubisco homologues, lower ZC tends to occur in organisms with higher optimal growth temperature, and there are broad changes in ZC in whole-genome protein compositions in microbes from different environments. Energetic costs calculated from thermodynamic models suggest that thermophilic organisms exhibit molecular adaptation to not only high temperature but also the reducing nature of many hydrothermal fluids. A view of protein metabolism that depends on the chemical conditions of cells and environments raises new questions linking biochemical processes to changes on evolutionary timescales.
|
10.1098/rsif.2013.1095
|
biorxiv
| 427 |
10.1101/004176
|
A novel paradigm for auditory discrimination training with social reinforcement in songbirds
|
Kirill Tokarev;Ofer Tchernichovski;
|
Kirill Tokarev
|
Hunter College, CUNY
|
2014-04-14
|
1
|
New Results
|
cc_by_nc
|
Neuroscience
|
https://www.biorxiv.org/content/early/2014/04/14/004176.source.xml
|
Zebra finches are a highly social, gregarious, species and eagerly engage in vocal communication. We have developed a training apparatus that allows training zebra finches to discriminate socially reinforced and aversive vocal stimuli. In our experiments, juvenile male zebra finches were trained to discriminate a song that was followed by a brief air puff (aversive) and a song that allowed them to stay in visual contact with another bird, audience (social song). During training, the birds learned quickly to avoid air puffs by escaping the aversive song within 2 sec. They escaped significantly more aversive songs than socially reinforced ones, and this effect grew stronger with the number of training sessions. Therefore, we propose this training procedure as an effective method to teach zebra finches to discriminate between different auditory stimuli, which may also be used as a broader paradigm for addressing social reinforcement learning. The apparatus can be built from commercially available parts, and we are sharing the controlling software on our website.
|
NA
|
biorxiv
| 429 |
10.1101/004218
|
Bridging the Genotype and the Phenotype: Towards An Epigenetic Landscape Approach to Evolutionary Systems Biology
|
Jose Davila-Velderrain;Elena R Alvarez-Buylla;
|
Elena R Alvarez-Buylla
|
Universidad Nacional Autonoma de Mexico
|
2014-04-14
|
1
|
New Results
|
cc_by_nc_nd
|
Systems Biology
|
https://www.biorxiv.org/content/early/2014/04/14/004218.source.xml
|
Understanding the mapping of genotypes into phenotypes is a central challenge of current biological research. Such mapping, conceptually represents a developmental mechanism through which phenotypic variation can be generated. Given the nongenetic character of developmental dynamics, phenotypic variation to a great extent has been neglected in the study of evolution. What is the relevance of considering this generative process in the study of evolution? How can we study its evolutionary consequences? Despite an historical systematic bias towards linear causation schemes in biology; in the post-genomic era, a systems-view to biology based on nonlinear (network) thinking is increasingly being adopted. Within this view, evolutionary dynamics can be studied using simple dynamical models of gene regulatory networks (GRNs). Through the study of GRN dynamics, genotypes and phenotypes can be unambiguously defined. The orchestrating role of GRNs constitutes an operational non-linear genotype-phenotype map. Further extension of these GRN models in order to explore and characterize an associated Epigenetic Landscape enables the study of the evolutionary consequences of both genetic and non-genetic sources of phenotypic variation within the same coherent theoretical framework. The merging of conceptually clear theories, computational/mathematical tools, and molecular/genomic data into coherent frameworks could be the basis for a transformation of biological research from mainly a descriptive exercise into a truly mechanistic, explanatory endeavor.
|
NA
|
biorxiv
| 430 |
10.1101/004226
|
Building a better frog trap: The benefits of mal-adaptive habitat choice for metapopulations with different life history strategies
|
Rosemary Hartman;Noam Ross;
|
Rosemary Hartman
|
University of California Davis
|
2014-04-15
|
1
|
New Results
|
cc_by_nc_nd
|
Ecology
|
https://www.biorxiv.org/content/early/2014/04/15/004226.source.xml
|
By spatially distributing offspring among several habitat patches in varying environments, an organism can \"hedge its bets\" to protect against bad conditions in any single patch. This strategy can maintain populations even when some or even all locations are, on average, population sinks. However, species may not have evolved this bet-hedging mechanism, especially when sink environments are anthropogenic \"traps\" - locations where traditional habitat cues have been altered. Using a model based on the life history of the Cascades frog (Rana cascadae), we examine the conditions that maximize growth in an environment with ecological traps created by the introduction of predators. In a temporally stochastic environment, maximum growth rates occur when some juveniles disperse to the trap. We then examine how different life histories and predation regimes affect the ability of an organism gain an advantage by bet-hedging, and find that bet-hedging can be less useful when the ecological trap drives adult, rather than juvenile, mortality.
|
NA
|
biorxiv
| 432 |
10.1101/004234
|
Genetic Influences on Brain Gene Expression in Rats Selected for Tameness and Aggression
|
Henrike Heyne;Susann Lautenschlaeger;Ronald Nelson;François Besnier;Maxime Rotival;Alexander Cagan;Rimma Kozhemyakina;Irina Plyusnina;Lyudmila Trut;Orjan Carlborg;Enrico Petretto;Leonid Kruglyak;Svante Pääbo;Torsten Schoeneberg;Frank Albert;
|
Henrike Heyne
|
University of Leipzig
|
2014-04-17
|
1
|
New Results
|
cc_by_nc_nd
|
Genomics
|
https://www.biorxiv.org/content/early/2014/04/17/004234.source.xml
|
Inter-individual differences in many behaviors are partly due to genetic differences, but the identification of the genes and variants that influence behavior remains challenging. Here, we studied an F2 intercross of two outbred lines of rats selected for tame and aggressive behavior towards humans for more than 64 generations. By using a mapping approach that is able to identify genetic loci segregating within the lines, we identified four times more loci influencing tameness and aggression than by an approach that assumes fixation of causative alleles, suggesting that many causative loci were not driven to fixation by the selection. We used RNA sequencing in 150 F2 animals to identify hundreds of loci that influence brain gene expression. Several of these loci colocalize with tameness loci and may reflect the same genetic variants. Through analyses of correlations between allele effects on behavior and gene expression, differential expression between the tame and aggressive rat selection lines, and correlations between gene expression and tameness in F2 animals, we identify the genes Gltscr2, Lgi4, Zfp40 and Slc17a7 as candidate contributors to the strikingly different behavior of the tame and aggressive animals.
|
10.1534/genetics.114.168948
|
biorxiv
| 433 |
10.1101/004267
|
Gradual divergence and diversification of mammalian duplicate gene functions
|
Raquel Assis;Doris Bachtrog;
|
Raquel Assis
|
Pennsylvania State University
|
2014-04-17
|
1
|
New Results
|
cc_no
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/04/17/004267.source.xml
|
Gene duplication provides raw material for the evolution of functional innovation. We recently developed a phylogenetic method to classify the evolutionary processes underlying the retention and functional evolution of duplicate genes by quantifying divergence of their gene expression profiles. Here, we apply our method to pairs of duplicate genes in eight mammalian genomes, using data from 11 distinct tissues to construct spatial gene expression profiles. We find that young mammalian duplicates are often functionally conserved, and that functional divergence gradually increases with evolutionary distance between species. Examination of expression patterns in genes with conserved and new functions supports the \"out-of-testes\" hypothesis, in which new genes arise with testis-specific functions and acquire functions in other tissues over time. While new functions tend to be tissue-specific, there is no bias toward expression in any particular tissue. Thus, duplicate genes acquire a diversity of functions outside of the testes, possibly contributing to the origin of a multitude of complex phenotypes during mammalian evolution.
|
NA
|
biorxiv
| 434 |
10.1101/004242
|
Exact Reconstruction of Gene Regulatory Networks using Compressive Sensing
|
Young Hwan Chang;Joe W. Gray;Claire J. Tomlin;
|
Claire J. Tomlin
|
Department of Electrical Engineering and Computer Sciences, University of California, Berkeley
|
2014-04-20
|
1
|
New Results
|
cc_no
|
Systems Biology
|
https://www.biorxiv.org/content/early/2014/04/20/004242.source.xml
|
BackgroundWe consider the problem of reconstructing a gene regulatory network structure from limited time series gene expression data, without any a priori knowledge of connectivity. We assume that the network is sparse, meaning the connectivity among genes is much less than full connectivity. We develop a method for network reconstruction based on compressive sensing, which takes advantage of the networks sparseness.\n\nResultsFor the case in which all genes are accessible for measurement, and there is no measurement noise, we show that our method can be used to exactly reconstruct the network. For the more general problem, in which hidden genes exist and all measurements are contaminated by noise, we show that our method leads to reliable reconstruction. In both cases, coherence of the model is used to assess the ability to reconstruct the network and to design new experiments. For each problem, a set of numerical examples is presented.\n\nConclusionsThe method provides a guarantee on how well the inferred graph structure represents the underlying system, reveals deficiencies in the data and model, and suggests experimental directions to remedy the deficiencies.
|
10.1186/s12859-014-0400-4
|
biorxiv
| 440 |
10.1101/004309
|
Regulatory variants explain much more heritability than coding variants across 11 common diseases
|
Alexander Gusev;S Hong Lee;Benjamin M Neale;Gosia Trynka;Bjarni J Vilhjalmsson;Hilary Finucane;Han Xu;Chongzhi Zang;Stephan Ripke;Eli Stahl;n/a Schizophrenia Working Group of the PGC;n/a SWE-SCZ Consortium;Anna K Kahler;Christina M Hultman;Shaun M Purcell;Steven A McCarroll;Mark Daly;Bogdan Pasaniuc;Patrick F Sullivan;Naomi R Wray;Soumya Raychaudhuri;Alkes L Price;
|
Alexander Gusev
|
Harvard School of Public Health
|
2014-04-21
|
1
|
New Results
|
cc_by
|
Genetics
|
https://www.biorxiv.org/content/early/2014/04/21/004309.source.xml
|
Common variants implicated by genome-wide association studies (GWAS) of complex diseases are known to be enriched for coding and regulatory variants. We applied methods to partition the heritability explained by genotyped SNPs [Formula] across functional categories (while accounting for shared variance due to linkage disequilibrium) to genotype and imputed data for 11 common diseases. DNaseI Hypersensitivity Sites (DHS) from 218 cell-types, spanning 16% of the genome, explained an average of 79% of [Formula] (5.1x enrichment; P < 10-20); further enrichment was observed at enhancer and cell-type specific DHS elements. The enrichments were much smaller in analyses that did not use imputed data or were restricted to GWAS-associated SNPs. In contrast, coding variants, spanning 1% of the genome, explained only 8% of [Formula] enrichment; P = 5 x 10-4). We replicated these findings but found no significant contribution from rare coding variants in an independent schizophrenia cohort genotyped on GWAS and exome chips.
|
NA
|
biorxiv
| 443 |
10.1101/004341
|
Quantifying selection in immune receptor repertoires
|
Yuval Elhanati;Anand Murugan;Curtis G Callan Jr.;Thierry Mora;Aleksandra Walczak;
|
Thierry Mora
|
Ecole Normale Supérieure
|
2014-04-21
|
1
|
New Results
|
cc_no
|
Immunology
|
https://www.biorxiv.org/content/early/2014/04/21/004341.source.xml
|
The efficient recognition of pathogens by the adaptive immune system relies on the diversity of receptors displayed at the surface of immune cells. T-cell receptor diversity results from an initial random DNA editing process, called VDJ recombination, followed by functional selection of cells according to the interaction of their surface receptors with self and foreign antigenic peptides. To quantify the effect of selection on the highly variable elements of the receptor, we apply a probabilistic maximum likelihood approach to the analysis of high-throughput sequence data from the {beta}-chain of human T-cell receptors. We quantify selection factors for V and J gene choice, and for the length and amino-acid composition of the variable region. Our approach is necessary to disentangle the effects of selection from biases inherent in the recombination process. Inferred selection factors differ little between donors, or between naive and memory repertoires. The number of sequences shared between donors is well-predicted by the model, indicating a purely stochastic origin of such \"public\" sequences. We find a significant correlation between biases induced by VDJ recombination and our inferred selection factors, together with a reduction of diversity during selection. Both effects suggest that natural selection acting on the recombination process has anticipated the selection pressures experienced during somatic evolution.
|
10.1073/pnas.1409572111
|
biorxiv
| 444 |
10.1101/004366
|
Quantitative comparison of single-cell sequencing methods using hippocampal neurons
|
Luwen Ning;Guan Wang;Zhoufang Li;Wen Hu;Qingming Hou;Yin Tong;Meng Zhang;Li Qin;Xiaoping Chen;Heng-Ye Man;Pinghua Liu;Jiankui He;
|
Jiankui He
|
South University of Science and Technology of China
|
2014-04-21
|
1
|
New Results
|
cc_by_nc_nd
|
Genomics
|
https://www.biorxiv.org/content/early/2014/04/21/004366.source.xml
|
Single-cell genomic analysis has grown rapidly in recent years and will find widespread applications in various fields of biology, including cancer biology, development, immunology, pre-implantation genetic diagnosis, and neurobiology. In this study, we amplified genomic DNA from individual hippocampal neurons using one of three single-cell DNA amplification methods (multiple annealing and looping-based amplification cycles (MALBAC), multiple displacement amplification (MDA), and GenomePlex whole genome amplification (WGA4)). We then systematically evaluated the genome coverage, GC-bias, reproducibility, and copy number variations among individual neurons. Our results showed that single-cell genome sequencing results obtained from the MALBAC and WGA4 methods are highly reproducible and have a high success rate. Chromosome-level and subchromosomal-level copy number variations among individual neurons can be detected.
|
NA
|
biorxiv
| 445 |
10.1101/004390
|
Notorious Novel Avian Influenza Viruses H10N8 and H7N9 in China in 2013 Co-originated from H9N2
|
Liang Chen;Feng Zhu;Chenglong Xiong;Zhijie Zhang;Lufang Jiang;Rui Li;Genming Zhao;Yue Chen;Qingwu Jiang;
|
Chenglong Xiong
|
Department of Sanitary Microbiology, School of Public Health, Fudan University
|
2014-04-21
|
1
|
New Results
|
cc_by
|
Pathology
|
https://www.biorxiv.org/content/early/2014/04/21/004390.source.xml
|
In 2013, two new avian influenza viruses (AIVs) H7N9 and H10N8 emerged in China caused worldwide concerns. Previous studies have studied their originations independently; this study is the first time to investigate their co-originating characteristics. Gene segments of assorted subtype influenza A viruses, as well as H10N8 and H7N9, were collected from public database. 26 With the help of series software, small and large-scale phylogenetic trees, mean evolutionary rates, and divergence years were obtained successionally. The results demonstrated the two AIVs co-originated from H9N2, and shared a spectrum of mutations in common on many key sites related to pathogenic, tropism and epidemiological characteristics. For a long time, H9N2 viruses had been circulated in eastern and southern China; poultry was the stable and lasting maintenance reservoir. High carrying rate of AIVs H9N2 in poultry had an extremely high risk of co-infections with other influenza viruses, which increased the risk of virus reassortment. It implied that novel AIVs reassortants based on H9N2 might appear and prevail at any time in China; therefore, surveillance of H9N2 AIVs should be given a high priority.
|
NA
|
biorxiv
| 446 |
10.1101/004424
|
Soft selective sweeps in complex demographic scenarios
|
Benjamin A Wilson;Dmitri Petrov;Philipp W Messer;
|
Benjamin A Wilson
|
Stanford University
|
2014-04-23
|
1
|
New Results
|
cc_by_nc
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/04/23/004424.source.xml
|
Recent studies have shown that adaptation from de novo mutation often produces so-called soft selective sweeps, where adaptive mutations of independent mutational origin sweep through the population at the same time. Population genetic theory predicts that soft sweeps should be likely if the product of the population size and the mutation rate towards the adaptive allele is sufficiently large, such that multiple adaptive mutations can establish before one has reached fixation; however, it remains unclear how demographic processes affect the probability of observing soft sweeps. Here we extend the theory of soft selective sweeps to realistic demographic scenarios that allow for changes in population size over time. We first show that population bottlenecks can lead to the removal of all but one adaptive lineage from an initially soft selective sweep. The parameter regime under which such 'hardening' of soft selective sweeps is likely is determined by a simple heuristic condition. We further develop a generalized analytical framework, based on an extension of the coalescent process, for calculating the probability of soft sweeps under arbitrary demographic scenarios. Two important limits emerge within this analytical framework: In the limit where population size fluctuations are fast compared to the duration of the sweep, the likelihood of soft sweeps is determined by the harmonic mean of the variance effective population size estimated over the duration of the sweep; in the opposing slow fluctuation limit, the likelihood of soft sweeps is determined by the instantaneous variance effective population size at the onset of the sweep. We show that as a consequence of this finding the probability of observing soft sweeps becomes a function of the strength of selection. Specifically, in species with sharply fluctuating population size, strong selection is more likely to produce soft sweeps than weak selection. Our results highlight the importance of accurate demographic estimates over short evolutionary timescales for understanding the population genetics of adaptation from de novo mutation.
|
10.1534/genetics.114.165571
|
biorxiv
| 448 |
10.1101/004440
|
The evolution of genetic diversity in changing environments
|
Oana Carja;Uri Liberman;Marcus W. Feldman;
|
Oana Carja
|
Stanford University
|
2014-04-23
|
1
|
New Results
|
cc_by_nc_nd
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/04/23/004440.source.xml
|
The production and maintenance of genetic and phenotypic diversity under temporally fluctuating selection and the signatures of environmental and selective volatility in the patterns of genetic and phenotypic variation have been important areas of focus in population genetics. On one hand, stretches of constant selection pull the genetic makeup of populations towards local fitness optima. On the other, in order to cope with changes in the selection regime, populations may evolve mechanisms that create a diversity of genotypes. By tuning the rates at which variability is produced, such as the rates of recombination, mutation or migration, populations may increase their long-term adaptability. Here we use theoretical models to gain insight into how the rates of these three evolutionary forces are shaped by fluctuating selection. We compare and contrast the evolution of recombination, mutation and migration under similar patterns of environmental change and show that these three sources of phenotypic variation are surprisingly similar in their response to changing selection. We show that knowing the shape, size, variance and asymmetry of environmental runs is essential for accurate prediction of genetic evolutionary dynamics.
|
10.1073/pnas.1417664111
|
biorxiv
| 449 |
10.1101/004465
|
A novel Bayesian method for inferring and interpreting the dynamics of adaptive landscapes from phylogenetic comparative data
|
Josef C Uyeda;Luke J Harmon;
|
Josef C Uyeda
|
University of Idaho
|
2014-04-23
|
1
|
New Results
|
cc_by_nd
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/04/23/004465.source.xml
|
Our understanding of macroevolutionary patterns of adaptive evolution has greatly increased with the advent of large-scale phylogenetic comparative methods. Widely used Ornstein-Uhlenbeck (OU) models can describe an adaptive process of divergence and selection. However, inference of the dynamics of adaptive landscapes from comparative data is complicated by interpretational difficulties, lack of identifiability among parameter values and the common requirement that adaptive hypotheses must be assigned a priori. Here we develop a reversible-jump Bayesian method of fitting multi-optima OU models to phylogenetic comparative data that estimates the placement and magnitude of adaptive shifts directly from the data. We show how biologically informed hypotheses can be tested against this inferred posterior of shift locations using Bayes Factors to establish whether our a priori models adequately describe the dynamics of adaptive peak shifts. Furthermore, we show how the inclusion of informative priors can be used to restrict models to biologically realistic parameter space and test particular biological interpretations of evolutionary models. We argue that Bayesian model-fitting of OU models to comparative data provides a framework for integrating of multiple sources of biological data--such as microevolutionary estimates of selection parameters and paleontological timeseries--allowing inference of adaptive landscape dynamics with explicit, process-based biological interpretations.
|
10.1093/sysbio/syu057
|
biorxiv
| 450 |
10.1101/004432
|
An integrated RNA and CRISPR/Cas toolkit for multiplexed synthetic circuits and endogenous gene regulation in human cells
|
Lior Nissim;Samuel D Perli;Alexandra Fridkin;Pablo Perez-Pinera;Timothy Lu;
|
Timothy Lu
|
Massachusetts Institute of Technology
|
2014-04-23
|
1
|
New Results
|
cc_no
|
Synthetic Biology
|
https://www.biorxiv.org/content/early/2014/04/23/004432.source.xml
|
RNA-based regulation, such as RNA interference, and CRISPR/Cas transcription factors (CRISPR-TFs), can enable scalable synthetic gene circuits and the modulation of endogenous networks but have yet to be integrated together. Here, we combined multiple mammalian RNA regulatory strategies, including RNA triple helix structures, introns, microRNAs, and ribozymes, with Cas9-based CRISPR-TFs and Cas6/Csy4-based RNA processing in human cells. We describe three complementary strategies for expressing functional gRNAs from transcripts generated by RNA polymerase II (RNAP II) promoters while allowing the harboring gene to be translated. These architectures enable the multiplexed expression of proteins and multiple gRNAs from a single compact transcript for efficient modulation of synthetic constructs and endogenous human promoters. We used these regulatory tools to implement tunable synthetic gene circuits, including multi-stage transcriptional cascades. Finally, we show that Csy4 can rewire regulatory connections in RNA-dependent gene circuits with multiple outputs and feedback loops to achieve complex functional behaviors. This multiplexable toolkit will be valuable for the construction of scalable gene circuits and the perturbation of natural regulatory networks in human cells for basic biology, therapeutic, and synthetic-biology applications.
|
NA
|
biorxiv
| 451 |
10.1101/002683
|
Evolutionary rates for multivariate traits: the role of selection and genetic variation
|
William Pitchers;Jason B. Wolf;Tom Tregenza;John Hunt;Ian Dworkin;
|
Ian Dworkin
|
Michigan State University
|
2014-05-05
|
3
|
New Results
|
cc_by_nc_nd
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/05/05/002683.source.xml
|
A fundamental question in evolutionary biology is the relative importance of selection and genetic architecture in determining evolutionary rates. Adaptive evolution can be described by the multivariate breeders equation [Formula], which predicts evolutionary change for a suite of phenotypic traits [Formula] as a product of directional selection acting on them ({beta}) and the genetic variance-covariance matrix for those traits (G). Despite being empirically challenging to estimate, there are enough published estimates of G and {beta} to allow for synthesis of general patterns across species. We use published estimates to test the hypotheses that there are systematic differences in the rate of evolution among trait types, and that these differences are in part due to genetic architecture. We find evidence some evidence that sexually selected traits exhibit faster rates of evolution compared to life-history or morphological traits. This difference does not appear to be related to stronger selection on sexually selected traits. Using numerous proposed approaches to quantifying the shape, size and structure of G we examine how these parameters relate to one another, and how they vary among taxonomic and trait groupings. Despite considerable variation, they do not explain the observed differences in evolutionary rates.
|
10.1098/rstb.2013.0252
|
biorxiv
| 456 |
10.1101/002899
|
An experimentally determined evolutionary model dramatically improves phylogenetic fit
|
Jesse D Bloom;
|
Jesse D Bloom
|
Fred Hutchinson Cancer Research Center
|
2014-04-27
|
4
|
New Results
|
cc_by
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/04/27/002899.source.xml
|
All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here I demonstrate an alternative: experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses.
|
10.1093/molbev/msu173
|
biorxiv
| 458 |
10.1101/003723
|
READemption - A tool for the computational analysis of deep-sequencing-based transcriptome data
|
Konrad Ulrich Förstner;Jörg Vogel;Cynthia Mira Sharma;
|
Cynthia Mira Sharma
|
Research Centre for Infectious Diseases
|
2014-05-19
|
3
|
New Results
|
cc_by
|
Bioinformatics
|
https://www.biorxiv.org/content/early/2014/05/19/003723.source.xml
|
SummaryRNA-Seq has become a potent and widely used method to qualitatively and quantitatively study transcriptomes. In order to draw biological conclusions based on RNA-Seq data, several steps some of which are computationally intensive, have to be taken. Our READemption pipeline takes care of these individual tasks and integrates them into an easy-to-use tool with a command line interface. To leverage the full power of modern computers, most subcommands of READemption offer parallel data processing. While READemption was mainly developed for the analysis of bacterial primary transcriptomes, we have successfully applied it to analyze RNA-Seq reads from other sample types, including whole transcriptomes, RNA immunoprecipitated with proteins, not only from bacteria, but also from eukaryotes and archaea.\n\nAvailability and ImplementationREADemption is implemented in Python and is published under the ISC open source license. The tool and documentation is hosted at http://pythonhosted.org/READemption (DOI:10.6084/m9.figshare.977849).\n\[email protected]; [email protected]
|
10.1093/bioinformatics/btu533
|
biorxiv
| 460 |
10.1101/004457
|
Cell size regulation in bacteria
|
Ariel Amir;
|
Ariel Amir
|
Harvard University
|
2014-04-24
|
2
|
New Results
|
cc_no
|
Biophysics
|
https://www.biorxiv.org/content/early/2014/04/24/004457.source.xml
|
Various bacteria such as the canonical gram negative Escherichia coli or the well-studied gram positive Bacillus subtilis divide symmetrically after they approximately double their volume. Their size at division is not constant, but is typically distributed over a narrow range. Here, we propose an analytically tractable model for cell size control, and calculate the cell size and inter-division time distributions, and the correlations between these variables. We suggest ways of extracting the model parameters from experimental data, and show that existing data for E. coli supports partial size control, and a particular explanation: a cell attempts to add a constant volume from the time of initiation of DNA replication to the next initiation event. This hypothesis accounts for the experimentally observed correlations between mother and daughter cells as well as the exponential dependence of size on growth rate.\n\nPACS numbers: 87.17.Ee, 87.17.Aa, 87.10.Mn, 87.81Tt
|
10.1103/PhysRevLett.112.208102
|
biorxiv
| 461 |
10.1101/004259
|
Disentangling Multidimensional Spatio-Temporal Data into their Common and Aberrant Responses
|
Young Hwan Chang;Jim Korkola;Dhara N. Amin;Mark M. Moasser;Jose M. Carmena;Joe W. Gray;Claire J. Tomlin;
|
Claire J. Tomlin
|
Department of Electrical Engineering and Computer Sciences, University of California, Berkeley
|
2014-04-28
|
2
|
New Results
|
cc_no
|
Systems Biology
|
https://www.biorxiv.org/content/early/2014/04/28/004259.source.xml
|
With the advent of high-throughput measurement techniques, scientists and engineers are starting to grapple with massive data sets and encountering challenges with how to organize, process and extract information into meaningful structures. Multidimensional spatio-temporal biological data sets such as time series gene expression with various perturbations over different cell lines, or neural spike trains across many experimental trials, have the potential to acquire insight across multiple dimensions. For this potential to be realized, we need a suitable representation to understand the data. Since a wide range of experiments and the unknown complexity of the underlying system contribute to the heterogeneity of biological data, we propose a method based on Robust Principal Component Analysis (RPCA), which is well suited for extracting principal components when there are corrupted observations. The proposed method provides us a new representation of these data sets in terms of a common and aberrant response. This representation might help users to acquire a new insight from data.\n\nAuthor SummaryOne of the most exciting trends and important themes in science and engineering involves the use of high-throughput measurement data. With different dimensions, for example, various perturbations, different doses of drug or cell lines characteristics, such multidimensional data sets enable us to understand commonalities and differences across multiple dimensions. A general question is how to organize the observed data into meaningful structures and how to find an appropriate similarity measure. A natural way of viewing these complex high dimensional data sets is to examine and analyze the large-scale features and then to focus on the interesting details. With this notion, we propose an RPCA-based method which models common variations as approximately the low-rank component and anomalies as the sparse component. We show that the proposed method is able to find distinct subtypes and classify data sets in a robust way without any prior knowledge by separating these common responses and abnormal responses.
|
10.1371/journal.pone.0121607
|
biorxiv
| 462 |
10.1101/004556
|
MOHCA-seq: RNA 3D models from single multiplexed proximity-mapping experiments
|
Clarence Cheng;Fang-Chieh Chou;Wipapat Kladwang;Siqi Tian;Pablo Cordero;Rhiju Das;
|
Rhiju Das
|
Stanford University
|
2014-04-25
|
1
|
New Results
|
cc_no
|
Biochemistry
|
https://www.biorxiv.org/content/early/2014/04/25/004556.source.xml
|
Large RNAs control myriad biological processes but challenge tertiary structure determination. We report that integrating multiplexed *OH cleavage analysis with tabletop deep sequencing (MOHCA-seq) gives nucleotide-resolution proximity maps of RNA structure from single straightforward experiments. After achieving 1-nm resolution models for RNAs of known structure, MOHCA-seq reveals previously unattainable 3D information for ligand-induced conformational changes in a double glycine riboswitch and the sixth community-wide RNA puzzle, an adenosylcobalamin riboswitch.
|
NA
|
biorxiv
| 464 |
10.1101/004382
|
Lack of association between Toll Like Receptor-2 &amp; Toll Like Receptor-4 Gene Polymorphisms and Iranian Asthmatics risk or features
|
hamid bahrami;saeed daneshmandi;Ali Akbar Pourfathollah;hasan haidarnazhad;
|
Ali Akbar Pourfathollah
|
tarbiat modares university
|
2014-04-28
|
1
|
New Results
|
cc_by_nc_nd
|
Immunology
|
https://www.biorxiv.org/content/early/2014/04/28/004382.source.xml
|
BackgroundAsthma as chronic inflammatory airway disease is considered to be the most common chronic disease that is involving genetic and environmental factors. Toll like receptors (TLRs) and other inflammatory mediators are important in modulation of inflammation. In this study we evaluated the role of TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms in the asthma susceptibility, progress, control levels and lung functions in Iranian subjects.\n\nMethodsOn 99 asthmatic patients and 120 normal subjects, TLR2 Arg753Gln and TLR4 Asp299Gly polymorphism were evaluated by PCR-RFLP method recruiting Msp1 and Nco1 restriction enzymes, respectively. IgE serum levels by ELISA technique were determined and asthma diagnosis, treatment and control levels were considered using standard schemes and criteria.\n\nResultsOur results indicated that the genotype and allele frequencies of the TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms were not significantly different between control subjects and asthmatics (p > 0.05) or even in asthma features such as IgE levels, asthma history and pulmonary factors (p > 0.05).\n\nConclusionsMeanwhile some previous studies indicated TLRs and their polymorphisms role in asthma incidence and features, our data demonstrated that TLR2 Arg753Gln and TLR4 Asp299Gly gene variants were not risk factor of asthma or its features in Iranian patients. Genetic complexity, ethnicity, influence of other genes or polymorphisms may overcome these polymorphisms in our asthmatics.
|
10.1016/j.meegid.2012.11.009
|
biorxiv
| 469 |
10.1101/004580
|
Regulatory RNA design through evolutionary computation and strand displacement
|
William Rostain;Thomas E Landrain;Guillermo Rodrigo;Alfonso Jaramillo;
|
Alfonso Jaramillo
|
University of Warwick
|
2014-04-28
|
1
|
New Results
|
cc_no
|
Synthetic Biology
|
https://www.biorxiv.org/content/early/2014/04/28/004580.source.xml
|
The discovery and study of a vast number of regulatory RNAs in all kingdoms of life over the past decades has allowed the design of new synthetic RNAs that can regulate gene expression in vivo. Riboregulators, in particular, have been used to activate or repress gene expression. However, to accelerate and scale up the design process, synthetic biologists require computer-assisted design tools, without which riboregulator engineering will remain a case-by-case design process requiring expert attention. Recently, the design of RNA circuits by evolutionary computation and adapting strand displacement techniques from nanotechnology has proven to be suited to the automated generation of DNA sequences implementing regulatory RNA systems in bacteria. Herein, we present our method to carry out such evolutionary design and how to use it to create various types of riboregulators, allowing the systematic de novo design of genetic control systems in synthetic biology.
|
10.1007/978-1-4939-1878-2_4
|
biorxiv
| 471 |
10.1101/004499
|
In vivo generation of DNA sequence diversity for cellular barcoding
|
Ian Peikon;Diana Gizatullina;Anthony Zador;
|
Anthony Zador
|
Cold Spring Harbor Laboratory
|
2014-04-24
|
1
|
New Results
|
cc_by_nc
|
Synthetic Biology
|
https://www.biorxiv.org/content/early/2014/04/24/004499.source.xml
|
Heterogeneity is a ubiquitous feature of biological systems. A complete understanding of such systems requires a method for uniquely identifying and tracking individual components and their interactions with each other. We have developed a novel method of uniquely tagging individual cells in vivo with a genetic \"barcode\" that can be recovered by DNA sequencing. We demonstrate the feasibility of this technique in bacterial cells. This method should prove useful in tracking interactions of cells within a network, and/or heterogeneity within complex biological samples.
|
10.1093/nar/gku604
|
biorxiv
| 472 |
10.1101/004622
|
Graph-based data integration predicts long-range regulatory interactions across the human genome
|
Sofie Demeyer;Tom Michoel;
|
Tom Michoel
|
The University of Edinburgh
|
2014-04-29
|
1
|
New Results
|
cc_no
|
Bioinformatics
|
https://www.biorxiv.org/content/early/2014/04/29/004622.source.xml
|
Transcriptional regulation of gene expression is one of the main processes that affect cell diversification from a single set of genes. Regulatory proteins often interact with DNA regions located distally from the transcription start sites (TSS) of the genes. We developed a computational method that combines open chromatin and gene expression information for a large number of cell types to identify these distal regulatory elements. Our method builds correlation graphs for publicly available DNase-seq and exon array datasets with matching samples and uses graph-based methods to filter findings supported by multiple datasets and remove indirect interactions. The resulting set of interactions was validated with both anecdotal information of known long-range interactions and unbiased experimental data deduced from Hi-C and CAGE experiments. Our results provide a novel set of high-confidence candidate open chromatin regions involved in gene regulation, often located several Mb away from the TSS of their target gene.
|
NA
|
biorxiv
| 473 |
10.1101/004614
|
Characterizing a collective and dynamic component of chromatin immunoprecipitation enrichment profiles in yeast
|
Lucas D. Ward;Junbai Wang;Harmen J. Bussemaker;
|
Harmen J. Bussemaker
|
Columbia University
|
2014-04-29
|
1
|
New Results
|
cc_no
|
Genomics
|
https://www.biorxiv.org/content/early/2014/04/29/004614.source.xml
|
Recent chromatin immunoprecipitation (ChIP) experiments in fly, mouse, and human have revealed the existence of high-occupancy target (HOT) regions or hotspots that show enrichment across many assayed DNA-binding proteins. Similar co-enrichment observed in yeast so far has been treated as artifactual, and has not been fully characterized. Here we reanalyze ChIP data from both array-based and sequencing-based experiments to show that in the yeast S. cerevisiae, the collective enrichment phenomenon is strongly associated with proximity to noncoding RNA genes and with nucleosome depletion. DNA sequence motifs that confer binding affinity for the proteins are largely absent from these hotspots, suggesting that protein-protein interactions play a prominent role. The hotspots are condition-specific, suggesting that they reflect a chromatin state or protein state, and are not a static feature of underlying sequence. Additionally, only a subset of all assayed factors is associated with these loci, suggesting that the co-enrichment cannot be simply explained by a chromatin state that is universally more prone to immunoprecipitation. Together our results suggest that the co-enrichment patterns observed in yeast represent transcription factor co-occupancy. More generally, they make clear that great caution must be used when interpreting ChIP enrichment profiles for individual factors in isolation, as they will include factor-specific as well as collective contributions.
|
10.1186/1471-2164-15-494
|
biorxiv
| 474 |
10.1101/004648
|
Ontogenic, phenotypic, and functional characterization of XCR1+ dendritic cells leads to a consistent classification of intestinal dendritic cells based on the expression of XCR1 and SIRPα
|
Martina Becker;Steffen Güttler;Annabell Bachem;Evelyn Hartung;Ahmed Mora;Anika Jäkel;Andreas Hutloff;Volker Henn;Hans Werner Mages;Stephanie Gurka;Richard A. Kroczek;
|
Richard A. Kroczek
|
Robert Koch-Institute
|
2014-04-30
|
1
|
New Results
|
cc_no
|
Immunology
|
https://www.biorxiv.org/content/early/2014/04/30/004648.source.xml
|
In the past, lack of lineage markers confounded the classification of dendritic cells (DC) in the intestine and impeded a full understanding of their location and function. We have recently shown that the chemokine receptor XCR1 is a lineage marker for cross-presenting DC in the spleen. Now we provide evidence that intestinal XCR1+ DC largely, but not fully, overlap with CD103+ CD11b- DC, the hypothesized correlate of \"cross-presenting DC\" in the intestine, and are selectively dependent in their development on the transcription factor Batf3. XCR1+ DC are located in the villi and epithelial crypts of the lamina propria of the small intestine, the T cell zones of Peyers Patches, and in the T cell zones and sinuses of the draining mesenteric lymph node. Functionally, we could demonstrate for the first time that XCR1+ / CD103+ CD11b- DC excel in the cross-presentation of orally applied antigen. Together, our data show that XCR1 is a lineage marker for cross-presenting DC also in the intestinal immune system. Further, extensive phenotypic analyses reveal that expression of the integrin SIRP consistently demarcates the XCR1- DC population. We propose a simplified and consistent classification system for intestinal DC based on the expression of XCR1 and SIRP.
|
10.3389/fimmu.2014.00326
|
biorxiv
| 475 |
10.1101/004663
|
Functional knockout of forebrain protein 14-3-3 disrupts conditioned taste aversion learning
|
Adam Kimbrough;Yuying Wu;Yi Zhou;Thomas A. Houpt;
|
Thomas A. Houpt
|
Dept. Biological Science, Program in Neuroscience, Florida State University
|
2014-04-30
|
1
|
New Results
|
cc_no
|
Neuroscience
|
https://www.biorxiv.org/content/early/2014/04/30/004663.source.xml
|
Protein 14-3-3 isoforms are key to many cellular processes and are ubiquitous throughout the brain. 14-3-3 is a regulator of ser/thr phospho-signaling by binding and sequestering phosphorylated substrates including kinases, histone deactylases, and transcription factors. The role of protein 14-3-3 in conditioned taste aversion learning (CTA) has not previously been examined. We parameterized CTA learning in difopein- YFP transgenic mice, which have widespread by expression of the artificial peptide difopein in the forebrain, including the basolateral amygdala and insular cortex, resulting in functional knock-out (FKO) of all 14-3-3 isoforms . We found that a single pairing of saccharin or NaCl (CS) and LiCl injection (US) was not sufficient to induce CTA in FKO mice. Multiples pairings of CS and US did lead to CTA acquisition in the FKO mice; however, the CTA rapidly extinguished within 30 minutes to 24 hours after acquisition. Additionally, we found that 14-3-3 FKO mice have an attenuated visceral neuraxis response to LiCl as measured by c-Fos induction. The deficit in FKO was not due to an inability to discriminate or avoid tastants, because they showed normal unconditioned taste preferences for both palatable (saccharin, maltodextrin , low concentration NaCl) and unpalatable tastants (quinine, HCl, and high concentration NaCl) and they were able to reduce intake of a maltodextrin solution adulterated with quinine. The FKO did not have a global deficit in ingestive learning, because they were able to form a conditioned flavor-nutrient preference. Thus, FKO of forebrain 14-3-3 appears to disrupt CTA learning leading to forgetting, rapid extinction, or failure to reconsolidate. This further implicates ser/thr phospho-signaling pathways in the regulation of long-term CTA learning.
|
NA
|
biorxiv
| 476 |
10.1101/004655
|
Accounting for sources of bias and uncertainty in copy number-based statistical deconvolution of heterogeneous tumour samples
|
Christopher Yau;
|
Christopher Yau
|
University of Oxford
|
2014-04-30
|
1
|
New Results
|
cc_no
|
Bioinformatics
|
https://www.biorxiv.org/content/early/2014/04/30/004655.source.xml
|
Deconvolving heterogeneous tumour samples to identify constituent cell populations with differing copy number profiles using whole genome sequencing data is a challenging problem. Copy number calling algorithms have differential detection rates for different sizes and classes of copy number alterations. This paper describes how uncertainty in classification and differential detection rates can introduce biases in measures of clonal diversity. A simulation strategy is introduced that allows differential detection rates to be adjusted for and this process is shown to minimise bias.
|
NA
|
biorxiv
| 477 |
10.1101/004689
|
Detection and Polarization of Introgression in a Five-taxon Phylogeny
|
James B Pease;Matthew W. Hahn;
|
James B Pease
|
Indiana University
|
2014-05-01
|
1
|
New Results
|
cc_by_nc_nd
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/05/01/004689.source.xml
|
In clades of closely related taxa, discordant genealogies due to incomplete lineage sorting (ILS) can complicate the detection of introgression. The D-statistic (a.k.a. the ABBA/BABA test) was proposed to infer introgression in the presence of ILS for a four-taxon clade. However, the original D-statistic cannot be directly applied to a symmetric five-taxon phylogeny, and the direction of introgression cannot be inferred for any tree topology. Here we explore the issues associated with previous methods for adapting the D-statistic to a larger tree topology, and propose new \"DFOIL\" tests to infer both the taxa involved in and the direction of introgressions for a symmetric five-taxon phylogeny. Using theory and simulations, we find that previous modifications of the D-statistic to five-taxon phylogenies incorrectly identify both the pairs of taxa exchanging migrants as well as the direction of introgression. The DFOIL statistics are shown to overcome this deficiency and to correctly determine the direction of introgressions. The DFOIL tests are relatively simple and computationally inexpensive to calculate, and can be easily applied to various phylogenomic datasets. In addition, our general approach to the problem of introgression detection could be adapted to larger tree topologies and other models of sequence evolution.
|
10.1093/sysbio/syv023
|
biorxiv
| 480 |
10.1101/004713
|
Spatial localization of recent ancestors for admixed individuals
|
Wen-Yun Yang;Alexander Platt;Charleston Wen-Kai Chiang;Eleazar Eskin;John Novembre;Bogdan Pasaniuc;
|
Bogdan Pasaniuc
|
University of California Los Angeles
|
2014-05-04
|
1
|
New Results
|
cc_no
|
Genetics
|
https://www.biorxiv.org/content/early/2014/05/04/004713.source.xml
|
Ancestry analysis from genetic data plays a critical role in studies of human disease and evolution. Recent work has introduced explicit models for the geographic distribution of genetic variation and has shown that such explicit models yield superior accuracy in ancestry inference over non-model-based methods. Here we extend such work to introduce a method that models admixture between ancestors from multiple sources across a geographic continuum. We devise efficient algorithms based on hidden Markov models to localize on a map the recent ancestors (e.g. grandparents) of admixed individuals, joint with assigning ancestry at each locus in the genome. We validate our methods using empirical data from individuals with mixed European ancestry from the POPRES study and show that our approach is able to localize their recent ancestors within an average of 470Km of the reported locations of their grandparents. Furthermore, simulations from real POPRES genotype data show that our method attains high accuracy in localizing recent ancestors of admixed individuals in Europe (an average of 550Km from their true location for localization of 2 ancestries in Europe, 4 generations ago). We explore the limits of ancestry localization under our approach and find that performance decreases as the number of distinct ancestries and generations since admixture increases. Finally, we build a map of expected localization accuracy across admixed individuals according to the location of origin within Europe of their ancestors.\n\nAuthor SummaryInferring ancestry from genetic data forms a fundamental problem with applications ranging from localizing disease genes to inference of human history. Recent approaches have introduced models of genetic variation as a function of geography and have shown that such models yield high accuracies in ancestry inference from genetic data. In this work we propose methods for modeling the mixing of genetic data from different sources (i.e. admixture process) in a genetic-geographic continuum and show that using these methods we can accurately infer the ancestry of the recent ancestors (e.g. grandparents) from genetic data.
|
10.1534/g3.114.014274
|
biorxiv
| 481 |
10.1101/004705
|
Comparison of Y-chromosomal lineage dating using either evolutionary or genealogical Y-STR mutation rates
|
Chuan-Chao Wang;Li Hui;
|
Li Hui
|
Fudan University
|
2014-05-03
|
1
|
New Results
|
cc_by_nc
|
Genetics
|
https://www.biorxiv.org/content/early/2014/05/03/004705.source.xml
|
We have compared the Y chromosomal lineage dating between sequence data and commonly used Y-SNP plus Y-STR data. The coalescent times estimated using evolutionary Y-STR mutation rates correspond best with sequence-based dating when the lineages include the most ancient haplogroup A individuals. However, the times using slow mutated STR markers with genealogical rates fit well with sequence-based estimates in main lineages, such as haplogroup CT, DE, K, NO, IJ, P, E, C, I, J, N, O, and R. In addition, genealogical rates lead to more plausible time estimates for Neolithic coalescent sublineages compared with sequence-based dating.
|
NA
|
biorxiv
| 482 |
10.1101/004739
|
Automatic Classification of Human Epithelial Type 2 Cell Indirect Immunofluorescence Images using Cell Pyramid Matching
|
Arnold Wiliem;Conrad Sanderson;Yongkang Wong;Peter Hobson;Rodney Minchin;Brian Lovell;
|
Conrad Sanderson
|
NICTA
|
2014-05-05
|
1
|
New Results
|
cc_no
|
Bioinformatics
|
https://www.biorxiv.org/content/early/2014/05/05/004739.source.xml
|
This paper describes a novel system for automatic classification of images obtained from Anti-Nuclear Antibody (ANA) pathology tests on Human Epithelial type 2 (HEp-2) cells using the Indirect Immunofluorescence (IIF) protocol. The IIF protocol on HEp-2 cells has been the hallmark method to identify the presence of ANAs, due to its high sensitivity and the large range of antigens that can be detected. However, it suffers from numerous shortcomings, such as being subjective as well as time and labour intensive. Computer Aided Diagnostic (CAD) systems have been developed to address these problems, which automatically classify a HEp-2 cell image into one of its known patterns (eg. speckled, homogeneous). Most of the existing CAD systems use handpicked features to represent a HEp-2 cell image, which may only work in limited scenarios. We propose a novel automatic cell image classification method termed Cell Pyramid Matching (CPM), which is comprised of regional histograms of visual words coupled with the Multiple Kernel Learning framework. We present a study of several variations of generating histograms and show the efficacy of the system on two publicly available datasets: the ICPR HEp-2 cell classification contest dataset and the SNPHEp-2 dataset.
|
10.1016/j.patcog.2013.10.014
|
biorxiv
| 483 |
10.1101/004747
|
Pre-trial exogenous visual flicker does not affect behavioral or EEG signatures of conflict processing
|
Michael X Cohen;Fraser William Steel;
|
Michael X Cohen
|
University of Amsterdam
|
2014-05-05
|
1
|
New Results
|
cc_by
|
Neuroscience
|
https://www.biorxiv.org/content/early/2014/05/05/004747.source.xml
|
Activity in the theta frequency band (4-8 Hz) over medial prefrontal regions has been consistently implicated in top-down cognitive control processes, including recognizing and resolving response conflict. It remains an unanswered question whether these theta-band dynamics are a neural mechanism of cognitive control, or instead are epiphenomenal to the neural computational machinery but are useful indices of brain function. Here we addressed this question by attempting to boost conflict processing (or its EEG theta-band signatures) via pre-trial exogenous theta-band visual flicker. Although the flicker successfully entrained posterior brain networks, there were no effects of flicker on behavior or on EEG signatures of conflict processing. In this paper, we detail our attempts and discuss possible future directions for using exogenous flicker in the study of the role of endogenous brain oscillations in conflict processing.
|
NA
|
biorxiv
| 484 |
10.1101/004796
|
N-BLR, a primate-specific non-coding transcript, modulates the epithelial-to-mesenchymal transition and leads to colorectal cancer invasion and migration
|
Isidore Rigoutsos;Sang Kil Lee;Su Youn Nam;Tina Catela Ivkovic;Martin Pichler;Simona Rossi;Peter Clark;Jing Yi;Hui Ling;Masayoshi Shimizu;Roxana Simona Redis;Maitri Yogen Shah;Xinna Zhang;Eun Jung Jung;Aristotelis Tsirigos;Li Huang;Jana Ferdin;Roberta Gafa;Riccardo Spizzo;Milena Nicoloso;Maryam Shariati;Aida Tiron;Jen Jen Yeh;Raul Teruel;Sonia Melo;Lianchun Xiao;Elsa Renee Flores;Massimo Negrini;Menashe Bar Eli;Sendurai Mani;Chang-Gong Liu;Ioana Berindan-Neagoe;Manel Esteller;Michael Keating;Giovanni Lanza;George Calin;
|
George Calin
|
Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houst
|
2014-05-06
|
1
|
New Results
|
cc_no
|
Genomics
|
https://www.biorxiv.org/content/early/2014/05/06/004796.source.xml
|
Non-coding RNAs have been commanding increasingly greater attention in recent years as the few that have been functionalized to date play important roles in key cellular processes. Here we show that N-BLR, a ~900 bp non-coding RNA, modulates the epithelial-to-mesenchymal transition, increases colorectal cancer invasion, and functions as a migration enabler by affecting the expression of ZEB1 and E-cadherin. In patients with colorectal cancer, N-BLR expression associates with tumor stage and invasion potential. As N-BLR contains several instances of a category of DNA motifs known as pyknons, we also designed a custom-made array to investigate the possibility that other pyknon loci may be transcribed. For several of the loci probed by the array we found that the corresponding pyknons are differentially expressed between cancer and normal tissue samples. Taken together the data suggest that a systematic study of other pyknon-containing non-coding RNAs like N-BLR may be warranted in the context of colorectal cancer.
|
NA
|
biorxiv
| 487 |
10.1101/004846
|
Cooperation between Noncanonical Ras Network Mutations in Cancer
|
Edward C Stites;Paul C Trampont;Lisa B Haney;Scott F Walk;Kodi S Ravichandran;
|
Edward C Stites
|
Washington University School of Medicine
|
2014-05-06
|
1
|
New Results
|
cc_no
|
Cancer Biology
|
https://www.biorxiv.org/content/early/2014/05/06/004846.source.xml
|
Cancer develops after the acquisition of a collection of mutations that together create the cancer phenotype. How collections of mutations work together within a cell, and whether there is selection for certain combinations of mutations, are not well understood. Using a Ras signaling network mathematical model we tested potential synergistic combinations within the Ras network. Intriguingly, our modeling, including a \"computational random mutagenesis\" approach, and subsequent experiments revealed that mutations of the tumor suppressor gene NF1 can amplify the effects of mutations in multiple other components of the Ras pathway, including weakly activating, noncanonical, Ras mutants. Since conventional wisdom holds that mutations within the same pathway do not co-occur, it was surprising that modeling and experiments both suggested a functional benefit for co-occurring Ras pathway mutations. Furthermore, we analyzed >3900 sequenced cancer specimens from the Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA) and we uncovered an increased rate of co-occurrence between mutations the model predicted could display synergy. Overall, these data suggest that selective combinations of Ras pathway mutations could serve the role of cancer \"driver\". More generally, this work presents a mechanism by which the context created by one mutation influences the evolutionary trajectories of cancer development, and this work suggests that mutations that result in \"network instability\" may promote cancer in a manner analogous to genomic instability.
|
10.1016/j.celrep.2014.12.035
|
biorxiv
| 488 |
10.1101/004820
|
Some plants don&#146;t play games: An ideal free distribution explains the root production of plants that do not engage in a tragedy of the commons game.
|
Gordon McNickle;Joel S Brown;
|
Gordon McNickle
|
Wilfrid Laurier University
|
2014-05-07
|
2
|
New Results
|
cc_no
|
Ecology
|
https://www.biorxiv.org/content/early/2014/05/07/004820.source.xml
|
This is the pre-peer-reviewed version of the following article: G.G. McNickle and J.S. Brown. (2014) An ideal free distribution explains the root production of plants that do not engage in a tragedy of the commons game. Journal of Ecology. DOI: 10.1111/1365-2745.12259, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/1365-2745.12259/abstract\n\nO_LIGame theoretic models that seek to predict the most competitive strategy plants use for competition in soil are clear; they generally predict that over-proliferation of roots is the only evolutionarily stable strategy. However, empirical studies are equally clear that not all plants employ this strategy of over-proliferation of roots. Here, our goal was to develop and test an alternative non-game theoretic model that can be used to develop alternative hypotheses for plants that do not appear to play games.\nC_LIO_LIThe model is similar to previous models, but does not use a game theoretic optimization criterion. Instead, plants use only nutrient availability to select a root allocation strategy, ignoring neighbours. To test the model we compare root allocation and seed yield of plants grown either alone or with neighbours.\nC_LIO_LIThe model predicted plants that do not sense neighbours (or ignore neighbours) should allocate roots relative to resource availability following an ideal free distribution. This means that if a soil volume of quality R contains x roots, then a soil volume of quality R/n will contain x/n roots. The experimental data were consistent with this prediction. That is, plants grown with 1.2g of slow release fertilizer resources produced 0.043 g of roots, while plants grown with neighbours, or plants grown with half as much fertilizer produced half as much root mass (0.026g, and 0.24g respectively). Seed yield followed a similar pattern.\nC_LIO_LIThis model presents an alternative predictive framework for those plant species that do not seem to play a tragedy of the commons game for belowground competition.\nC_LIO_LISynthesis: It remains unclear why some plants do not engage in belowground games for competition. Models suggest over-proliferation is an unbeatable evolutionary stable strategy, yet plants that do not play the game apparently coexist with plants that do. We suggest that a greater understanding of trade-offs among traits that are important for other biotic interactions (above-ground competition, enemy defence, mutualisms) will lead to a greater understanding of why some species over-proliferate roots when in competition but other species do not.\nC_LI
|
10.1111/1365-2745.12259
|
biorxiv
| 490 |
10.1101/004853
|
MOSAIC EPIGENETIC DYSREGULATION OF ECTODERMAL CELLS IN AUTISM SPECTRUM DISORDER
|
Esther R. Berko;Masako Suzuki;Faygel Beren;Christophe Lemetre;Christine M. Alaimo;R. Brent Calder;Karen Ballaban-Gil;Batya Gounder;Kaylee Kampf;Jill Kirschen;Shahina B. Maqbool;Zeineen Momin;David M. Reynolds;Natalie Russo;Lisa Shulman;Edyta Stasiek;Jessica Tozour;Maria Valicenti-McDermott;Shenglong Wang;Brett S. Abrahams;Joseph Hargitai;Dov Inbar;Zhengdong Zhang;Joseph D. Buxbaum;Sophie Molholm;John J. Foxe;Robert W. Marion;Adam Auton;John Greally;
|
John Greally
|
Albert Einstein College of Medicine
|
2014-05-06
|
1
|
New Results
|
cc_by_nc
|
Genomics
|
https://www.biorxiv.org/content/early/2014/05/06/004853.source.xml
|
DNA mutational events are increasingly being identified in autism spectrum disorder (ASD), but the potential additional role of dysregulation of the epigenome in the pathogenesis of the condition remains unclear. The epigenome is of interest as a possible mediator of environmental effects during development, encoding a cellular memory reflected by altered function of progeny cells. Advanced maternal age (AMA) is associated with an increased risk of having a child with ASD for reasons that are not understood. To explore whether AMA involves covert aneuploidy or epigenetic dysregulation leading to ASD in the offspring, we tested an homogeneous ectodermal cell type from 47 individuals with ASD compared with 48 typically developing (TD) controls born to mothers of [≥]35 years, using a quantitative genome-wide DNA methylation assay. We show that DNA methylation patterns are dysregulated in ectodermal cells in these individuals, having accounted for confounding effects due to subject age, sex and ancestral haplotype. We did not find mosaic aneuploidy or copy number variability to occur at differentially-methylated regions in these subjects. Of note, the loci with distinctive DNA methylation were found at genes expressed in the brain and encoding protein products significantly enriched for interactions with those produced by known ASD-causing genes, representing a perturbation by epigenomic dysregulation of the same networks compromised by DNA mutational mechanisms. The results indicate the presence of a mosaic subpopulation of epigenetically-dysregulated, ectodermally-derived cells in subjects with ASD. The epigenetic dysregulation observed in these ASD subjects born to older mothers may be associated with aging parental gametes, environmental influences during embryogenesis or could be the consequence of mutations of the chromatin regulatory genes increasingly implicated in ASD. The results indicate that epigenetic dysregulatory mechanisms may complement and interact with DNA mutations in the pathogenesis of the disorder.\n\nAUTHOR SUMMARYOlder mothers have a higher than expected risk of having a child with an autism spectrum disorder (ASD). The reason for this increased risk is unknown. The eggs of older mothers are more prone to abnormalities of chromosome numbers, suggesting this as one possible mechanism of the increased ASD risk. Age is also associated with a loss of control of epigenetic regulatory patterns that govern gene expression, indicating a second potential mechanism. To test both possibilities, we sampled cells from the same developmental origin as the brain, and performed genome-wide tests looking for unusual chromosome numbers and DNA methylation patterns. The studies were performed on individuals with ASD and typically developing controls, all born to mothers at least 35 years of age at the time of birth. We found the cells from individuals with ASD to have changes in DNA methylation at a number of loci, especially near genes encoding proteins known to interact with those already implicated in ASD. We conclude that epigenetic dysregulation occurring in gametes or early embryonic life may be one of the contributors to the development of ASD.
|
10.1371/journal.pgen.1004402
|
biorxiv
| 491 |
10.1101/004861
|
Missing kinaesthesia challenges precise naturalistic cortical prosthetic control
|
Ferran Galán;Mark R Baker;Kai Alter;Stuart N Baker;
|
Ferran Gal?n
|
Institute of Neuroscience, Newcastle University
|
2014-05-06
|
1
|
New Results
|
cc_by_nc_nd
|
Neuroscience
|
https://www.biorxiv.org/content/early/2014/05/06/004861.source.xml
|
A major assumption of brain-machine interface (BMI) research is that patients with disconnected neural pathways can still volitionally recall precise motor commands that could be decoded for naturalistic prosthetic control. However, the disconnected condition of these patients also blocks kinaesthetic feedback from the periphery, which has been shown to regulate centrally generated output responsible for accurate motor control. Here we tested how well motor commands are generated in the absence of kinaesthetic feedback by decoding hand movements from human scalp electroencephalography (EEG) in three conditions: unimpaired movement, imagined movement, and movement attempted during temporary disconnection of peripheral afferent and efferent nerves by ischemic nerve block. Our results suggest that the recall of cortical motor commands is impoverished in absence of kinaesthetic feedback, challenging the possibility of precise naturalistic cortical prosthetic control.
|
10.1002/hbm.22653
|
biorxiv
| 492 |
10.1101/004804
|
Visual areas exert feedforward and feedback influences through distinct frequency channels
|
Andre M Bastos;Julien Vezoli;Conrado A Bosman;Jan-Mathijs Schoffelen;Robert Oostenveld;Jarrod R Dowdall;Peter De Weerd;Henry Kennedy;Pascal Fries;
|
Pascal Fries
|
Ernst Strüngmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society
|
2014-05-06
|
1
|
New Results
|
cc_by_nc_nd
|
Neuroscience
|
https://www.biorxiv.org/content/early/2014/05/06/004804.source.xml
|
Visual cortical areas are thought to form a hierarchy and to subserve cognitive functions by interacting in both feedforward and feedback directions. While feedforward influences convey sensory signals, feedback influences modulate brain responses to a given sensory stimulus according to the current behavioural context. Many studies have demonstrated effects of feedback influences on feedforward driven responses and on behaviour. Also, anatomical projections in both directions have been identified. However, although these studies have revealed the anatomical paths and the neurophysiological consequences of influences in both directions, the neurophysiological mechanisms through which these influences are exerted remain largely elusive. Here we show that in the primate visual system, feedforward influences are carried by theta-band (~4 Hz) and gamma-band (~60-80 Hz) synchronization, and feedback influences by beta-band (~14-18 Hz) synchronization. These frequency-specific asymmetries in directed influences were revealed by simultaneous local field potential recordings from eight visual areas and an analysis of Granger-causal influences across all 28 pairs of areas. The asymmetries in directed influences correlated directly with asymmetries in anatomy and enabled us to build a visual cortical hierarchy from the influence asymmetries alone. Across different task periods, most areas stayed at their hierarchical position, whereas particularly frontal areas moved dynamically. Our results demonstrate that feedforward and feedback signalling use different frequency channels, which might subserve their differential communication requirements and lead to differential local consequences. The possibility to infer hierarchical relationships through functional data alone might make it possible to derive a cortical hierarchy in the living human brain.
|
10.1016/j.neuron.2014.12.018
|
biorxiv
| 493 |
10.1101/004788
|
A gene expression atlas of a bicoid-depleted Drosophila embryo reveals early canalization of cell fate
|
Max V Staller;Charless C Fowlkes;Meghan D.J. Bragdon;Zeba B. Wunderlich;Angela DePace;
|
Angela DePace
|
Harvard Medical School
|
2014-05-06
|
1
|
New Results
|
cc_by_nc_nd
|
Systems Biology
|
https://www.biorxiv.org/content/early/2014/05/06/004788.source.xml
|
In developing embryos, gene regulatory networks canalize cells towards discrete terminal fates. We studied the behavior of the anterior-posterior segmentation network in Drosophila melanogaster embryos depleted of a key maternal input, bicoid (bcd), by building a cellular- resolution gene expression atlas containing measurements of 12 core patterning genes over 6 time points in early development. With this atlas, we determine the precise perturbation each cell experiences, relative to wild type, and observe how these cells assume cell fates in the perturbed embryo. The first zygotic layer of the network, consisting of the gap and terminal genes, is highly robust to perturbation: all combinations of transcription factor expression found in bcd depleted embryos were also found in wild type embryos, suggesting that no new cell fates were created even at this very early stage. All of the gap gene expression patterns in the trunk expand by different amounts, a feature that we were unable to explain using two simple models of the effect of bcd depletion. In the second layer of the network, depletion of bcd led to an excess of cells expressing both even skipped and fushi tarazu early in the blastoderm stage, but by gastrulation this overlap resolved into mutually exclusive stripes. Thus, following depletion of bcd, individual cells rapidly canalize towards normal cell fates in both layers of this gene regulatory network. Our gene expression atlas provides a high resolution picture of a classic perturbation and will enable further modeling of canalization in this transcriptional network.
|
10.1242/dev.117796
|
biorxiv
| 495 |
10.1101/004895
|
Genetic dissection of MAPK-mediated complex traits across S. cerevisiae
|
Sebastian Treusch;Frank W Albert;Joshua S Bloom;Iulia E Kotenko;Leonid Kruglyak;
|
Leonid Kruglyak
|
Howard Hughes Medical Institute, Department of Human Genetics, Department of Biological Chemistry, U
|
2014-05-07
|
1
|
New Results
|
cc_no
|
Genetics
|
https://www.biorxiv.org/content/early/2014/05/07/004895.source.xml
|
Signaling pathways enable cells to sense and respond to their environment. Many cellular signaling strategies are conserved from fungi to humans, yet their activity and phenotypic consequences can vary extensively among individuals within a species. A systematic assessment of the impact of naturally occurring genetic variation on signaling pathways remains to be conducted. In S. cerevisiae, both response and resistance to stressors that activate signaling pathways differ between diverse isolates. Here, we present a quantitative trait locus (QTL) mapping approach that enables us to identify genetic variants underlying such phenotypic differences across the genetic and phenotypic diversity of S. cerevisiae. Using a Round-robin cross between twelve diverse strains, we determined the genetic architectures of phenotypes critically dependent on MAPK signaling cascades. Genetic variants identified fell within MAPK signaling networks themselves as well as other interconnected signaling pathways, illustrating how genetic variation can shape the phenotypic output of highly conserved signaling cascades.
|
10.1371/journal.pgen.1004913
|
biorxiv
| 496 |
10.1101/004911
|
Application of Global Transcriptome Data in Gene Ontology Classification and Construction of a Gene Ontology Interaction Network
|
Mario Fruzangohar;Esmaeil Ebrahimie;David L Adelson;
|
David L Adelson
|
University of Adelaide
|
2014-05-14
|
2
|
New Results
|
cc_by_nd
|
Bioinformatics
|
https://www.biorxiv.org/content/early/2014/05/14/004911.source.xml
|
Gene Ontology (GO) classification of statistically significant over/under expressed genes is a commonly used to interpret transcriptomics data in functional genomic analysis. In this approach, all significant genes contribute equally to the final GO classification regardless of their actual expression levels. However, the original level of gene expression can significantly affect protein production and consequently GO term enrichment, and genes with low expression levels can participate in the final GO enrichment through cumulative effects. In addition, GO terms have regulatory relationships that allow the construction of a regulatory network that incorporates gene expression levels to better study biological mechanisms. In this report, we have used gene expression levels in bacteria to determine GO term enrichments. This approach provided the opportunity to enrich GO terms across the entire transcriptome (instead of a subset of differentially expressed genes). In the second part, we show a dynamically developed enriched interaction network between Biological Process GO terms for any gene samples. This type of network presents regulatory relationships between GO terms and their genes. We then demonstrate the efficiency of these methods using public data from two important bacterial pathogens as models. We also explain how these methods help us understand potential pathogenesis mechanisms employed by these bacteria.
|
NA
|
biorxiv
| 498 |
10.1101/004903
|
Differential relationships between habitat fragmentation and within-population genetic diversity of three forest-dwelling birds
|
Benjamin Zuckerberg;Matt Carling;Roi Dor;Elise Ferree;Garth Spellman;Andrea Townsend;
|
Benjamin Zuckerberg
|
University of Wisconsin
|
2014-05-08
|
1
|
New Results
|
cc_by_nc_nd
|
Genetics
|
https://www.biorxiv.org/content/early/2014/05/08/004903.source.xml
|
Habitat fragmentation is a major driver of environmental change affecting wildlife populations across multiple levels of biological diversity. Much of the recent research in landscape genetics has focused on quantifying the influence of fragmentation on genetic variation among populations, but questions remain as to how habitat loss and configuration influences within-population genetic diversity. Habitat loss and fragmentation might lead to decreases in genetic diversity within populations, which might have implications for population persistence over multiple generations. We used genetic data collected from populations of three species occupying forested landscapes across a broad geographic region: Mountain Chickadee (Poecile gambeli; 22 populations), White-breasted Nuthatch (Sitta carolinensis; 13 populations) and Pygmy Nuthatch (Sitta pygmaea; 19 populations) to quantify patterns of haplotype and nucleotide diversity across a range of forest fragmentation. We predicted that fragmentation effects on genetic diversity would vary depending on dispersal capabilities and habitat specificity of the species. Forest aggregation and the variability in forest patch area were the two strongest landscape predictors of genetic diversity. We found higher haplotype diversity in populations of P. gambeli and S. carolinensis inhabiting landscapes characterized by lower levels of forest fragmentation. Conversely, S. pygmaea demonstrated the opposite pattern of higher genetic diversity in fragmented landscapes. For two of the three species, we found support for the prediction that highly fragmented landscapes sustain genetically less diverse populations. We suggest, however, that future studies should focus on species of varying life-history traits inhabiting independent landscapes to better understand how habitat fragmentation influences within-population genetic diversity.
|
NA
|
biorxiv
| 499 |
10.1101/004986
|
Spatial variation in water loss predicts terrestrial salamander distribution and population dynamics
|
William Peterman;Raymond D Semlitsch;
|
William Peterman
|
University of Illinois
|
2014-05-09
|
1
|
New Results
|
cc_by_nc_nd
|
Ecology
|
https://www.biorxiv.org/content/early/2014/05/09/004986.source.xml
|
Many patterns observed in ecology, such as species richness, life history variation, habitat use, and distribution have physiological underpinnings. For many ectothermic organisms temperature relations shape these patterns, but for terrestrial amphibians, water balance may supersede temperature as the most critical physiologically-limiting factor. Many amphibian species have little resistance to water loss, which restricts them to moist microhabitats and may significantly affect foraging, dispersal, and courtship. Using plaster models as surrogates for terrestrial plethodontid salamanders, we measured water loss under ecologically-relevant field conditions to estimate the duration of surface activity time across the landscape. Surface activity time was significantly affected by topography, solar exposure, canopy cover, maximum air temperature, and time since rain. Spatially, surface activity times were highest in ravine habitats and lowest on ridges. Surface activity time was a significant predictor of salamander abundance, as well as a predictor of successful recruitment; the probability of a juvenile salamander occupying an area with high surface activity time was two times greater than an area with limited predicted surface activity. Our results suggest that survival, recruitment, or both are demographic processes that are affected by water loss and the ability of salamanders to be surface active. Results from our study extend our understanding of plethodontid salamander ecology, emphasize the limitations imposed by their unique physiology, and highlight the importance of water loss to spatial population dynamics. These findings are timely to understanding the effects that fluctuating temperature and moisture conditions predicted for future climates will have on plethodontid salamanders.
|
10.1007/s00442-014-3041-4
|
biorxiv
| 500 |
10.1101/005017
|
Background selection as baseline for nucleotide variation across the Drosophila genome
|
Josep M Comeron;
|
Josep M Comeron
|
University of Iowa
|
2014-05-09
|
1
|
New Results
|
cc_by_nc_nd
|
Evolutionary Biology
|
https://www.biorxiv.org/content/early/2014/05/09/005017.source.xml
|
The constant removal of deleterious mutations by natural selection causes a reduction in neutral diversity and efficacy of selection at genetically linked sites (a process called Background Selection, BGS). Population genetic studies, however, often ignore BGS effects when investigating demographic events or the presence of other types of selection. To obtain a more realistic evolutionary expectation that incorporates the unavoidable consequences of deleterious mutations, we generated high-resolution landscapes of variation across the Drosophila melanogaster genome under a BGS scenario independent of polymorphism data. We find that BGS plays a significant role in shaping levels of variation across the entire genome, including long introns and intergenic regions distant from annotated genes. We also find that a very large percentage of the observed variation in diversity across autosomes can be explained by BGS alone, up to 70% across individual chromosome arms, thus indicating that BGS predictions can be used as baseline to infer additional types of selection and demographic events. This approach allows detecting several outlier regions with signal of recent adaptive events and selective sweeps. The use of a BGS baseline, however, is particularly appropriate to investigate the presence of balancing selection and our study exposes numerous genomic regions with the predicted signature of higher polymorphism than expected when a BGS context is taken into account. Importantly, we show that these conclusions are robust to the mutation and selection parameters of the BGS model. Finally, analyses of protein evolution together with previous comparisons of genetic maps between Drosophila species, suggest temporally variable recombination landscapes and thus, local BGS effects that may differ between extant and past phases. Because genome-wide BGS and temporal changes in linkage effects can skew approaches to estimate demographic and selective events, future analyses should incorporate BGS predictions and capture local recombination variation across genomes and along lineages.
|
10.1371/journal.pgen.1004434
|
biorxiv
| 503 |
10.1101/005025
|
Module organizational principles and dynamics in biological networks
|
Chun-Yu Lin;Tsai-ling Lee;Yi-Wei Lin;Yu-Shu Lo;Chih-Ta Lin;Jinn-Moon Yang;
|
Jinn-Moon Yang
|
Institute of Bioinformatics, National Chiao Tung University
|
2014-05-11
|
1
|
New Results
|
cc_no
|
Systems Biology
|
https://www.biorxiv.org/content/early/2014/05/11/005025.source.xml
|
A module is a group of closely related proteins that act in concert to perform specific biological functions through protein-protein interactions (PPIs) that occur in time and space. However, the underlying organizational principles of a module remain unclear. In this study, we collected CORUM module templates to infer respective module families, including 58,041 homologous modules in 1,678 species, and PPI families using searches of complete genomic database. We then derived PPI evolution scores (PPIES) and interface evolution scores (IES) to infer module elements, including core and ring components. Functions of core components were highly correlated (Pearsons r = 0.98) with those of 11,384 essential genes. In comparison with ring components, core proteins and PPIs were conserved in multiple species. Subsequently, protein dynamics and module dynamics of biological networks and functional diversities confirmed that core components form dynamic biological network hubs and play key roles in various biological functions. PPIES and IES can reflect module organization principles and protein/module dynamics in biological networks. On the basis of the analyses of gene essentiality, module dynamics, network topology, and gene co-expression, the module organizational principles can be described as follows: 1) a module consists of core and ring components; 2) the core components play major roles in biological functions and collaborate with ring components to perform certain functions in some cases; 3) the core components are conserved and essential in module dynamics in time and space.
|
NA
|
biorxiv
| 504 |
10.1101/004960
|
Mycoplasma stress response: adaptive regulation or broken brakes?
|
Pavel V Mazin;Gleb Y Fisunov;Alexey Y Gorbachev;Ilya A Altukhov;Tatiana A Semashko;Dmitry G Alexeev;Vadim M Govorun;
|
Gleb Y Fisunov
|
Research Institute of Physical-Chemical Medicine
|
2014-05-09
|
1
|
New Results
|
cc_no
|
Systems Biology
|
https://www.biorxiv.org/content/early/2014/05/09/004960.source.xml
|
The avian bacterial pathogen Mycoplasma gallisepticum is a good model for transcriptional regulation studies due to its small genome and relative simplicity. In this study, we used RNA-Seq experiments combined with MS-based proteomics to accurately map coding sequences (CDSs), transcription start sites (TSSs) and transcription terminators (TTs) and to decipher their roles in stress-induced transcriptional responses. We identified 1061 TSSs at an FDR (false discovery rate) of 10% and showed that almost all transcription in M. gallisepticum is initiated from classic TATAAT promoters, which are surrounded by A/T-rich sequences and rarely accompanied by a -35 element. Our analysis revealed the pronounced complexity of the operon structure: on average, each coding operon has one internal TSS and TT in addition to the primary ones. Our new transcriptomic approach based on the intervals between the two closest transcription initiators and/or terminators allowed us to identify two classes of TTs: strong, unregulated and hairpin-containing TTs and weak, heat shock-regulated and hairpinless TTs. Comparing the gene expression levels under different conditions (such as heat, osmotic and peroxide stresses) revealed widespread and divergent transcription regulation in M. gallisepticum. Modeling suggested that the structure of the core promoter plays a major role in gene expression regulation. We have shown that the heat stress activation of cryptic promoters combined with the suppression of hairpinless TTs leads to widespread, seemingly non-functional transcription.
|
NA
|
biorxiv
| 505 |
10.1101/005074
|
CasFinder: Flexible algorithm for identifying specific Cas9 targets in genomes
|
John Aach;Prashant Mali;George M Church;
|
John Aach
|
Harvard Medical School
|
2014-05-12
|
1
|
New Results
|
cc_by
|
Genomics
|
https://www.biorxiv.org/content/early/2014/05/12/005074.source.xml
|
CRISPR/Cas9 systems enable many molecular activities to be efficiently directed in vivo to user-specifiable DNA sequences of interest, including generation of dsDNA cuts and nicks, transcriptional activation and repression, and fluorescence. CRISPR targeting relies on base pairing of short RNA transcripts with their target DNA sequences that must also be adjacent to fixed DNA motifs. However, rules for Cas9 targeting specificity are incompletely known. With increasing numbers of Cas9 systems being developed and deployed in more and more organisms, there is now strong need for a flexible and rational method for finding Cas9 sites with low off-targeting potential. We address this through the CasFinder system, which we demonstrate by generating human and mouse exome-wide catalogs of specific sites for three varieties of Cas9 - S. pyogenes, S. thermophilus (ST1), and N. meningitidis - that each target 56-74% of all exons. We also generate reduced sets of up to 3 targets per gene for use in high-throughput Cas9-based gene knockout screens that target 75-80% of all genes.
|
NA
|
biorxiv
| 509 |
10.1101/005058
|
Diversity and evolution of centromere repeats in the maize genome
|
Paul Bilinski;Kevin Distor;Jose Gutierrez-Lopez;Gabriela Mendoza Mendoza;Jinghua Shi;R. Kelly Dawe;Jeffrey Ross-Ibarra;
|
Jeffrey Ross-Ibarra
|
University of California Davis
|
2014-05-12
|
1
|
New Results
|
cc_by
|
Genomics
|
https://www.biorxiv.org/content/early/2014/05/12/005058.source.xml
|
Centromere repeats are found in most eukaryotes and play a critical role in kinetochore formation. Though CentC repeats exhibit considerable diversity both within and among species, little is understood about the mechanisms that drive cen- tromere repeat evolution. Here, we use maize as a model to investigate how a complex history involving polyploidy, fractionation, and recent domestication has impacted the diversity of the maize CentC repeat. We first validate the existence of long tan- dem arrays of repeats in maize and other taxa in the genus Zea. Although we find considerable sequence diversity among CentC copies genome-wide, genetic similar- ity among repeats is highest within these arrays, suggesting that tandem duplica- tions are the primary mechanism for the generation of new copies. Genetic clustering analyses identify similar sequences among distant repeats, and simulations suggest that this pattern may be due to homoplasious mutation. Although the two ancestral subgenomes of maize have contributed nearly equal numbers of centromeres, our analysis shows that the vast majority of all CentC repeats derive from one of the parental genomes. Finally, by comparing maize with its wild progenitor teosinte, we find that the abundance of CentC has decreased through domestication while the peri- centromeric repeat Cent4 has drastically increased.
|
10.1007/s00412-014-0483-8
|
biorxiv
| 510 |
10.1101/005066
|
Independent Theta Phase Coding Accounts for CA1 Population Sequences and Enables Flexible Remapping
|
Angus Chadwick;Mark C. W. van Rossum;Matthew F. Nolan;
|
Matthew F. Nolan
|
University of Edinburgh
|
2014-05-12
|
1
|
New Results
|
cc_no
|
Neuroscience
|
https://www.biorxiv.org/content/early/2014/05/12/005066.source.xml
|
Populations of hippocampal place cells encode an animals past, current and future location through sequences of action potentials generated within each cycle of the network theta rhythm. These sequential representations have been suggested to result from temporally coordinated synaptic interactions within and between cell assemblies. In contrast, we show that a model based on rate and phase coding in independent neurons is sufficient to explain the organization of CA1 population activity during theta states. We show that CA1 population activity can be described as an evolving traveling wave that exhibits phase coding, rate coding, spike sequences and that generates an emergent population theta rhythm. We identify measures of global remapping and intracellular theta dynamics as critical for distinguishing mechanisms for pacemaking and coordination of sequential population activity. Our analysis suggests that independent coding enables flexible generation of sequential population activity within the duration of a single theta cycle.
|
10.7554/eLife.03542
|
biorxiv
| 512 |
10.1101/004978
|
Evidences of a cytotoxic activity of S-adenosylmethionine on OCI-AML3 cells
|
Kathrin Aprile von Hohenstaufen;Irina Puoti;Marisa Meloni;Barbara De Servi;
|
Kathrin Aprile von Hohenstaufen
|
Liber Augustalis Biomedical Research Association
|
2014-05-08
|
1
|
New Results
|
cc_no
|
Pharmacology and Toxicology
|
https://www.biorxiv.org/content/early/2014/05/08/004978.source.xml
|
BackgroundThe acute myeloid leukemia (AML) cell line OCI-AML3, carrying both NPM1 mutation A and the heterozygous DNMT3A R882C mutation, represents the model for in vitro studies on AML with mutated NPM11. AML with mutated NPM1 harbours a hypo-methylated profile distinct from those of the other AML subtypes2. This characteristic is probably related to the inhibitory effect of the mutant DNMT3A on the wild type protein3. S-adenosylmethionine (SAM) is a universal methyl donor acting as a coenzyme of DNMT3A. There are growing evidences of the antineoplastic effect of SAM in vitro and in murine models of gastric cancer, colon cancer and hepatocellular carcinoma, where SAM induces the downregulation of several oncogenes4-10. Moreover SAM upregulates the expression of DNMT enzymes in lung cancer cells11. In our knowledge there are no published data exploring the effect of SAM on the growth of OCI-AML3 cells and its ability to modulate DNMT3A activity in this cell line.
Study design and methodsThe present data have been generated between August 2013 and April 2014 at the VITROSCREEN facilities in Milan-ITALY. We used a 3-(4,5-dimethylthiazol-2-yl)-2,5-dephenyl tetrazolium bromide (MTT) assay to assess the cytotoxic effect of SAM iodide (Sigma-Aldrich) on OCI-AML3 cells (DSMZ Leibniz Institut). We analyzed then the ability of SAM to induce apoptosis by Tali Image-Based Cytometer (green Annexin V - Alexa Fluor 488 for apoptotic cells, red propidium and green Annexin V-Alexa Fluor 488 for necrotic cells).
ResultsThe MTT assays were performed after having treated the OCI-AML3 cells with various concentrations of the indicated drug for 24 hours. We observed no significant effects on cells viability using 0.5M, 10 M and 100 M of SAM (data not shown). In contrast, a dose dependent cytotoxic effect of SAM on OCI-AML3 cells was evident for concentrations equal or superior to 500 M, with an IC50 of 500 M (Figure 1). Since a Cmax of 211(SD 94)M after single intravenous infusion of SAM was previously reported in healthy voluntarees12, we decided to investigate the cytotoxic effect of SAM for concentrations close to 211 M using the MTT test. A significant dose dependent reduction of the cells viability was observed with SAM 200M (62,74% viable cells) and SAM 300M (53.32% viable cells), (Figure 2). The Apoptosis assay after 24 hours of treatment with SAM showed no differences in the percentages of apoptotic cells between the OCI-AML3 cells treated with SAM 300-500-2500 M and the untreated cells (data not shown). After 72 hours, only a minimal effect on the amount of apoptotic cells was obtained, while a clear dose dependent increase in the proportion of dead cells was noted (Figure 3), confirming the results of the aforementioned MTT tests.
O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/004978v1_fig1.gif" ALT="Figure 1">
View larger version (12K):
[email protected]@23bd30org.highwire.dtl.DTLVardef@59a9c5org.highwire.dtl.DTLVardef@98e377_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO MTT assay after 24 h exposure of OCI-AML3 cells to SAM at 0.5 mM, 2.5 mM and 10 mM. CN= negative control, untreated cells. SAM=S-Adenosylmethionine. Percentages of viable cells are reported. Both SAM treated cells and CN were tested in triplicate samples.
C_FIG O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/004978v1_fig2.gif" ALT="Figure 2">
View larger version (16K):
[email protected]@17e1d00org.highwire.dtl.DTLVardef@a213c5org.highwire.dtl.DTLVardef@c01c13_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 2.C_FLOATNO MTT assay after 24 h exposure of OCI-AML3 cells to SAM at 200 M (0.2mM), 300 M, 400 M, 500 M, 1000 M, 2500M. CN=negative control, untreated cells. SAM=S-Adenosylmethionine. Percentages of viable cells are reported. Both SAM treated cells and CN were tested in triplicate samples.
C_FIG O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/004978v1_fig3.gif" ALT="Figure 3">
View larger version (31K):
[email protected]@1825707org.highwire.dtl.DTLVardef@1f99a6org.highwire.dtl.DTLVardef@a08020_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 3.C_FLOATNO Percentages of Living, Dead and Apoptotic OCI-AML3 cells assessed by Tali image based cytometer after 72 hours treatment with different concentrations of SAM, and after 72 hours in medium (CN=negative control). Both SAM treated cells and CN were tested in duplicate samples.
C_FIG ConclusionsSAM showed remarkable in vitro cytotoxic activity on OCI-AML3 cells at concentrations similar to those achievable in humans after intravenous administration. SAM is not able to induce apoptosis of OCI-AML3 cells in vitro after 72 hours of treatment. However, the increase in the amount of dead cells after SAM treatment may be due to mechanisms other than apoptosis. In order to verify if the observed cytotoxicity was mediated by the enzymatic activity of DNMT3A, we planned to repeat the cytotoxicity assays after DNMT3A silencing. The in vivo antineoplastic effect of SAM could be assessed in NOD/SCID mice engrafted with OCI-AML3 cells.
Authors contributionKAvH wrote the study rationale, designed the study, interpreted the data and wrote the article; IP revised the article, MM and BDS planned and interpreted the experiments and BDS performed the experiments.
|
NA
|
biorxiv
| 513 |
10.1101/005090
|
Cosi2 : An efficient simulator of exact and approximate coalescent with selection
|
Ilya Shlyakhter;Pardis C. Sabeti;Stephen F. Schaffner;
|
Ilya Shlyakhter
|
Broad Institute, Harvard University
|
2014-05-14
|
1
|
New Results
|
cc_no
|
Genetics
|
https://www.biorxiv.org/content/early/2014/05/14/005090.source.xml
|
MotivationEfficient simulation of population genetic samples under a given demographic model is a prerequisite for many analyses. Coalescent theory provides an efficient framework for such simulations, but simulating longer regions and higher recombination rates remains challenging. Simulators based on a Markovian approximation to the coalescent scale well, but do not support simulation of selection. Gene conversion is not supported by any published coalescent simulators that support selection.\n\nResultsWe describe cosi2, an efficient simulator that supports both exact and approximate coalescent simulation with positive selection. cosi2 improves on the speed of existing exact simulators, and permits further speedup in approximate mode while retaining support for selection. cosi2 supports a wide range of demographic scenarios including recombination hot spots, gene conversion, population size changes, population structure and migration.\n\ncosi2 implements coalescent machinery efficiently by tracking only a small subset of the Ancestral Recombination Graph, sampling only relevant recombination events, and using augmented skip lists to represent tracked genetic segments. To preserve support for selection in approximate mode, the Markov approximation is implemented not by moving along the chromosome but by performing a standard backwards-in-time coalescent simulation while restricting coalescence to node pairs with overlapping or near-overlapping genetic material. We describe the algorithms used by cosi2 and present comparisons with existing selection simulators.\n\nAvailabilityA free C++ implementation of cosi2 is available at http://broadinstitute.org/[~]ilya/cosi2.\n\[email protected]
|
10.1093/bioinformatics/btu562
|
biorxiv
| 514 |
10.1101/005124
|
When genomes collide: multiple modes of germline misregulation in a dysgenic syndrome of Drosophila virilis
|
Mauricio A. Galdos;Alexandra A. Erwin;Michelle L. Wickersheim;Chris C. Harrison;Kendra D. Marr;Justin Blumenstiel;
|
Justin Blumenstiel
|
University of Kansas
|
2014-05-13
|
1
|
New Results
|
cc_by
|
Genetics
|
https://www.biorxiv.org/content/early/2014/05/13/005124.source.xml
|
In sexually reproducing species the union of gametes that are not closely related can result in genomic incompatibility. Hybrid dysgenic syndromes represent a form of genomic incompatibility that can arise when transposable element (TE) abundance differs between two parents. When TEs lacking in the female parent are transmitted paternally, a lack of corresponding silencing small RNAs (piRNAs) transmitted through the female germline can lead to TE mobilization in progeny. The epigenetic nature of this phenomenon is demonstrated by the fact that genetically identical females of the reciprocal cross are normal. Here we show that in the hybrid dysgenic syndrome of Drosophila virilis, an excess of paternally inherited TE families leads not only to increased expression of these TEs, but also coincides with derepression of TEs in equal abundance within parents. Moreover, TE derepression is stable as flies age and associated with piRNA biogenesis defects for only some TEs. At the same time, TE activation is associated with a genome wide shift in the distribution of endogenous gene expression and an increase in abundance of off-target genic piRNAs. To identify regions of the maternal genome that most protect against dysgenesis, we performed an F3 backcross analysis. We find that pericentric regions play a dominant role in maternal protection. This F3 backcross approach additionally allowed us to clarify the properties of genic paramutation in D. virilis. Overall, results support a model in which early germline events in dysgenesis establish a chronic, stable state of mis-expression that is maintained through adulthood.\n\nSuch early events in the germline that are mediated by parent-of-origin effects may be important in determining patterns of gene expression in natural populations.\n\nAuthor SummaryTransposable elements (TE) are selfish elements that code for the function of copying themselves. More than half the human genome is comprised of such elements. Studies in the fruit flies Drosophila melanogaster and D. virilis have been important in demonstrating a role for RNA silencing by piwi-interacting RNAs (piRNAs) in protecting the genome against these harmful elements. These small RNAs are capable of recognizing TE mRNAs and mediating their destruction by Argonaute proteins. They are also transmitted by the female germline to offspring in order to maintain a stable genome across generations. When males carrying a particular TE family are crossed with females lacking the element, the mother is unable to provide genome defense via complementary piRNAs that target the element. This leads to excess TE activation in the germline and sterility. This phenomenon is known as hybrid dysgenesis. In this article we characterize the genomic landscape of TE destabilization that occurs in hybrid dysgenesis in D. virilis. Previous studies had demonstrated that multiple TEs mobilized during hybrid dysgenesis. We demonstrate that this mobilization of multiple TEs is associated with activation of additional TEs in the germline. In addition, we find that TE activation leads to the production of off-target genic piRNAs that cause reduced expression of highly expressed genes. Finally, we show that genic off-target effects of piRNA silencing can contribute to parent-of-origin effects on gene expression. Similar phenomena may influence patterns of gene expression in the germline of natural populations.
|
NA
|
biorxiv
| 515 |
10.1101/005181
|
A new insight for the screening of potential β-lactamase inhibitors
|
Vijai Singh;Dharmendra Kumar Chaudhary;
|
Vijai Singh
|
Department of Biotechnology, Invertis University, Bareilly- Lucknow NH-24, Bareilly 243123, India
|
2014-05-15
|
2
|
New Results
|
cc_by
|
Bioinformatics
|
https://www.biorxiv.org/content/early/2014/05/15/005181.source.xml
|
The {beta}-lactamase produces by Aeromonas hydrophila which enables to hydrolyze and inactivate {beta}- lactam ring of antibiotics. The homology modeling was used to generate the 3-D model of {beta}-lactamase by using known template 3-D structure. The stereochemical quality and torsion angle of 3-D model were validated. Total eleven effective drugs have been selected and targeted the active amino acid residues in {beta}-lactamase. The drugs were derivative of {beta}-lactam ring antibiotics and screening was made by docking. Out of 11 drugs, 3 drugs (Ampicillin, Astreonam and Sultamicillin) were found to be more potent on the basis of robust binding energy between protein-drug interactions. Additionally, homology of {beta}-lactamase of A. hydrophila resembled with other pathogenic bacteria that used for phylogeny analysis. These findings suggest a new insight for better understanding and useful for designing of novel potent drugs.
|
NA
|
biorxiv
| 517 |
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