High-speed genetics test for infants
A group of scientists led by Dr. Stephen Kingsmore at Mercy Children's Hospital in Kansas City has developed a high-speed genetics test that can produce a diagnosis within 26 hours. The researchers worked alongside Illumina and Edico Genome as they almost halved the time for the delivery of a diagnosis from the previous 50-hour screening time﻿. The new method is cheaper and so will reduce costs for patients to around $20,000.

A breakthrough in high-speed genetic testing made possible in part by two San Diego companies can deliver a diagnosis in just 26 hours — and with more accuracy than the previous 50-hour screening, its creators announced Tuesday.

Experts said quicker sequencing has the potential of helping the 10 percent of newborns who end up in neonatal intensive care units with severe and undiagnosed symptoms, from seizures to heart problems. Rapidly determining the cause of these anomalies can influence treatment decisions, in some cases saving a life or avoiding lifelong mental impairment.

The new technique was published by a team of researchers with Children’s Mercy Hospital in Kansas City, Mo. That team is led by Dr. Stephen Kingsmore, who was recently named as the inaugural CEO of the genomics institute at Rady Children’s Hospital San Diego.

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Kingsmore and his colleagues worked with local sequencing giant Illumina and Torrey Pines bioinformatics processing start-up Edico Genome to sharply reduce the amount of time it takes to decode and analyze the genomes of children and their parents.

Kingsmore believes that a half-dozen advancements mentioned in Tuesday’s report can together help make genomic sequencing a reality for thousands of children every year.

He said research in Kansas City using the 26-hour test with a small number of patients primed him for the task of folding whole-genome-based genetic diagnosis into the standard of care at Rady’s, which recently received a $120 million donation from philanthropists Ernest and Evelyn Rady to help push the goal forward.

“We’ve not yet put this into production. That’s why I’m here in San Diego, to take this technology and put it into production at scale,” Kingsmore said.

The new paper got immediate attention from the genetics world.

Dr. Hakon Hakonarson, director of the Center for Applied Genomics at The Children’s Hospital of Philadelphia, said the results are unprecedented.

“Dr. Kingsmore deserves very significant credit for what he has done here. He has done what no one else has,” Hakonarson said.

However, he added that 26-hour results will not revolutionize clinical care until they become much cheaper. The new technique costs slightly less than the price of the 50-hour method, which is about $20,000 for a child and his or her parents, including analysis of the genomic data.

In comparison, traditional sequencing can be as cheap as $1,000 per individual with Illumina’s latest HiSeq X Ten system. That figure does not include the expense of post-sequencing analysis.

Illumina worked to increase the speed of its 2500 series sequencers to enable the 26-hour turnaround. Special techniques shortened the time it took to complete the sequencing steps from 25 to 18 hours.

The machines break DNA samples into bits for analysis, and then computers assemble millions of resulting data snippets into a single digital record with each nucleotide’s identity recorded in the correct order. This task took more than 14 hours during the 50-hour process using a supercomputing network.

Now, there is significant time savings thanks to the use of DRAGEN, a custom-built computing platform made by Edico Genome. DRAGEN is able to grind through the alignment step in only 10 minutes.

Kingsmore said he was skeptical about the technology when he was first approached about using it during a technology conference.

“I was like, ‘Yeah, right, uh huh.’ But when we tried it, it actually outperformed what they had promised,” Kingsmore said.

What’s more, he said, the DRAGEN processor delivers more accurate results — including fewer false positives and negatives — than other technology.

The size of the human genome makes precision essential, he said.

“The genome is a big place, with 3.3 billion letters, so even if your specificity is off by a couple of percentage points, suddenly you can have tens of millions of false-positive results,” Kingsmore said.

Pieter van Rooyen, Edico’s chief executive, said his company is excited to see its product as part of a technology that helps children with greater urgency. The arcane and abstract work of circuit and algorithm design is more satisfying when it eventually connects with real patients, he said.

“It’s extremely gratifying ...,” van Rooyen said.

While the 26-hour test can be used for patients young or old, its speed is of special significance to newborns. Getting results promptly can save babies who might otherwise die from undiagnosed genetic anomalies.

Kingsmore said he recently worked with a child in Kansas City who had very low blood-sugar level, and that traditional tests could not pinpoint the cause quickly. A rapid-turnaround, whole-genome sequencing found a mutation that causes the pancreas to produce too much insulin, resulting in potentially deadly low blood-sugar levels, he said.

Once the cause was identified, it was clear that removing a portion of the child’s pancreas, but not the whole organ, was the best option.

“That baby’s now home, alive and healthy,” Kingsmore said.

For the record: A previous version of this story reversed the name of Children’s Mercy Hospital in Kansas City. The hospital is in Missouri, not Kansas.