16 Clinical OMICs November/December 2017 www.clinicalomics.com
Diagnostics
Ring in the New
Rady Children's Hospital Introduces
NovaSeq for Newborn Diagnoses
by Kevin Davies
O
ver the past few years, Stephen Kingsmore has pio-
neered the use of clinical next-gen sequencing for the
diagnosis of babies admitted into the newborn intensive
care unit (NICU). That expertise was honed at Children's
Mercy Hospital in Kansas City, before Kingsmore moved in
2015 to the Rady Children's Hospital in San Diego.
In a presentation at the American Society of Human Genet-
ics annual conference, Kingsmore presented his vision for
enhancing and expediting the pipeline, which he believes
will become widely adopted at children's hospitals around
the world. Kingsmore already holds the Guinness World
Record for the fastest genetic diagnosis—26 hours—which
was set using Illumina's HiSeq 2500 sequencing instrument
(in rapid run mode).
The push for rapid sequencing is a hallmark of the work
of Kingsmore and his team at Rady Children's. "Dr. King-
smore in a pioneer, especially in the field of rapid whole
genome sequencing for critically ill children in the NICU/
PICU," said Martin Reese, founder, president, and CEO of
computational genomics company Fabric Genomics, which
provides a platform for clinical interpretation of variants to
the hospital's program. "Very few doctors have the in-depth
genetics training and deep knowledge of sequencing and
interpreting disease-causing variants."
About 5 percent of all newborns are admitted to the
NICU. The ensuing diagnostic odyssey can be short or long.
"Some babies will die. Others will be discharged without a
diagnosis," said Kinsgmore. At the center of Kingsmore's
vision is Illumina's latest sequencer, the NovaSeq 6000. The
goal is "to obtain a diagnosis as rapidly as possible" which
would enable "scalable, high-throughput analysis to be
used at various hospitals around the world."
In brief, the Rady pipeline uses natural language process-
ing to extract information from the patient's medical record.
This is converted into a standard vocabulary that enables
pattern recognition to match against some 8,000 known
genetic diseases, which are listed in rank order.
Whole-genome sequencing is performed on the newborn
and parents (if possible). For the most urgent cases, the new-
born's genome is currently sequenced on the HiSeq 2500,
which typically takes about 30 hours. The sequence data
are fed into a rapid analysis pipeline using Edico Genome's
DRAGEN processing platform and Fabric Genomics' Opal
clinical variant platform for interpretation. "We can obtain
a provisional diagnosis in two days if [the newborn is] sick
enough to warrant that," Kingsmore said.
Fuel the Vision
The Rady team's experience with the first 42 cases in this
paradigm "fuel the vision," said Kingsmore. Eighteen (40
Dr. Stepehn Kingsmore stands with a new NovaSeq 6000 and a flow
cell at Rady Children's Hospital.
E.
Grafton
/
Rady
Children's
Institute
for
Genomic
Medicine