Clinical OMICS

NOV-DEC 2017

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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Page 18 of 47 November/December 2017 Clinical OMICs 17 percent) of the 42 newborns received a diagnosis after genome analysis, of which 13 obtained a change in dis- ease management. Overall, 11 (24 per- cent) of NICU newborns sequenced received a change in outcome. "These are remarkable findings that are going to change the way medi- cine is practiced in the NICU," said Kingsmore. "This [approach] is still not well advertised, well known or well implemented in children's hospitals around the world," Kingsmore said. "We believe this will become a para- digm for treating children around the world." Kingsmore described a recent suc- cessful outcome in a case known as Infant 6041. A two-day-old baby girl named Sebastiana experienced seizures beginning just 16 hours after delivery. Standard drugs were ineffective or required such high doses that the baby was lethargic and couldn't feed. Within 68 hours, Kingsmore's team had reached a diagnosis of Ohtahara syndrome, having discovered a de novo missense mutation in a gene encod- ing a potassium channel, KCNQ2. A change in treatment resulted in control over the seizures, and Sebastiana was discharged 18 days after admission. A similar case at the hospital had been admitted a year earlier; but without the full genome analysis, it took doctors two months to reach the same diagnosis, and the patient in that case has major brain damage. Moreover, the reduced time to Sebastiana's diagnosis resulted in cost savings of about $180,000. Enter the NovaSeq While the current Rady pipeline is among the most efficient in the world, there is room for improvement. "The HiSeq 2500 does a beautiful job," Kingsmore said, "but it only runs one sample at a time and it is rather costly." Rady has just validated the Nova- Seq instrument, placing it into clin- ical (CLIA/CAP) production earlier this month. "Almost everything is different about the platform," King- smore said. Initial results on 52 whole genomes sequenced showed excellent coverage of the entire genome (compa- rable to the HiSeq) including known Mendelian disease genes. Kingsmore said he favors the 2x100-nucleotide (compared to 2x150) approach, which he says saves a lot of time. Kinsgmore believes in 40x coverage for newborn screening. "That's our clinical specification," he said, adding that the NovaSeq offers "an exqui- sitively sensitive and specific test." Whereas the HiSeq 2500 produced a single human genome (at 40x cover- age) over about 26 hours, requiring two flow cells, the NovaSeq can gener- ate six genomes (also 40x) in a 24-hour run on a single flow-cell, for a third of the cost of the HiSeq. Kingsmore's groundbreaking work was recently profiled in TIME maga- zine in a story by Alice Park. He had hoped to announce an even shorter turnaround time, using a new tech- nology that would prepare the DNA library directly from a blood sample without having to extract the DNA as an intermediate step. But that tech- nique wasn't ready in time. pelicankate / Getty Images "Very few doctors have the in-depth genetics training and deep knowledge of sequencing and interpreting disease-causing variants." —Martin Reese, CEO, Farbric Genomics Fast, whole-genome sequencing is vital to helping the sickest babies born with a rare diesease.

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