Speed Record Set for Whole-Genome Sequencing

Stephen Kingsmore, M.D., D.Sc., and his team at Rady Children's Institute for Genomic Medicine (San Diego) were awarded the Guinness World Records title for fastest genetic diagnosis on Feb. 3 with a time of 19.5 hours. Kingsome set the previous record of 26 hours in 2015, while at Children's Mercy (Kansas City, Mo.).

"Our evolving ability to find the answers to medical mysteries through rapid whole genome sequencing is providing hope for babies and children with rare, genetic diseases," said Kingsmore, president and CEO of Rady's, in a statement. "By speeding delivery of genomic insights, we are equipping physicians with the information they need to provide precision care for the youngest and most fragile patients."

Rady's sequencing workflow is engineered to both accelerate and scale up genomic data interpretation—reducing the time and cost of whole genome sequencing. The institute says that up to one-third of babies admitted to a neonatal intensive care unit in the United States have a genetic disease, with treatment currently available for more than 500 of these genetic diseases. Quick initiation of therapy in newborns can help prevent disabilities and life-threatening illnesses associated with 70 of these conditions.

The institute began performing genomic sequencing in July 2016. By the end of January 2018, the team reports having completed testing and interpretation of the genomes of more than 335 children enrolled in its research studies. Additionally, the institute reports that one-third of the patients received a genomic diagnosis with 69 percent of those benefitting from an immediate change in clinical care.

Work is now focused on building a research-to-bedside pipeline extending from Rady's to children's hospitals nationwide. "Our hope is that pediatric genomic medicine will one day become routine so that ultimately all children who need it can have access to this life-saving technology," says Kingsmore.

The record-setting analysis involved a collaboration between Rady and other technology and data-science companies. Together, the team optimized an "ultra- rapid, accurate, and scalable process" by integrating several time-saving technologies that shaved 6.5 hours off of the previous record. Partners included:

• Illumina (San Diego) - The Rady's team used Illumina's NovaSeq 6000 Sequencing System, a new generation of high-density flow cells that enable reassemblage in digital form, and the Nextera DNA Flex library preparation.

• Clinithink (Alpharetta, Ga.). Clinithink has a natural language processing platform that automatically extracts crucial phenotype information from a patient's electronic medical record.

• Diploid (Belgium) - Diploid's Moon variant interpretation software uses artificial intelligence to spot genetic mutations within sequenced genomic data and make a preliminary diagnosis of rare diseases in about 4 minutes.

• Edico Genome (San Diego) - Edico Genome's DRAGEN (Dynamic Read Analysis for GENomics) platform provides ultra-rapid sequence alignment and variant calling significantly increasing the speed of secondary analysis.

• Alexion (New Haven, Conn) - Alexion provided rare disease and data science expertise that enabled the translation of clinical information into a computable format for guided variant interpretation.

• Fabric Genomics (Oakland, Calif.) - Fabric's clinical decision support software, OPAL, enabled rapid diagnosis by helping to find the correct genetic cause of illnesses.

Takeaway: The increasing speed of whole-genome sequencing is bringing the prospect of its use for rapid clinical diagnostics closer to reality.