Whole Genome Sequencing Yields Clinical Information

Among acutely ill neonatal intensive care unit (NICU) patients, rapid whole genome sequencing (WGS) offers clinically useful information and substantial cost savings in comparison to the current standard of care.

It has been demonstrated that early diagnosis changes acute care management and that rapid WGS improves clinical care. A new study built on prior work by scientists showing that rapid WGS in neonates led to reduced time to diagnosis and better rates of diagnosis than previous practice.


A team of experts at Rady Children’s Institute for Genomic Medicine (San Diego, CA, USA) enrolled 98 NICU patients who were nominated by a treating physician and whose parents gave consent to participate. Enrolled infants had blood samples taken within 48-72 hours of NICU admission, with polymerase chain reaction-free WGS at 40-45X coverage performed on these samples within 3 to 7 days. The investigators translated into human phenotype ontology terms the phenotypic features of each baby and mapped them to potentially causative genetic diseases. They used commercial tools to align DNA sequences and identify variants. Board-certified geneticists curated all variants and clinicians confirmed all significant results.

In one-third of patients (34/98), rapid WGS yielded a genetic diagnosis, which led to changes in medical management in 28 neonates (80%). For example, unnecessary surgery may have been avoided, medications may have been changed to better target underlying diseases, or families may have been counseled about palliative care. Among the first 42 infants, the investigators calculated that rapid WGS led to USD 1.3 million in net cost savings in comparison to standard care the babies otherwise would have received.

Shimul Chowdhury, PhD, FACMG, the clinical laboratory director and first author of the study, said, “Eventually we would like to see rapid WGS as a reimbursable first-tier test for a proportion of infants in the NICU.” The investigators have launched partnerships with children’s hospitals in California and Minnesota to scale-up the rapid WGS process and to determine its clinical utility, cost-effectiveness, and ease of implementation in different institutions. The study was presented at the Annual meeting of the American Society of Human Genetics held October 17, to October 21, 2017, in Orlando, Florida, USA.

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Rady Children’s Institute for Genomic Medicine