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Genome Med. 2015 Sep 30;7:100. doi: 10.1186/s13073-015-0221-8.

A 26-hour system of highly sensitive whole genome sequencing for emergency management of genetic diseases.

Author information

1
Center for Pediatric Genomic Medicine, Children's Mercy, 2401 Gilham Road, Kansas City, MO, 64108, USA.
2
Department of Pediatrics, Children's Mercy, Kansas City, MO, 64108, USA.
3
Department of Pathology, Children's Mercy, Kansas City, MO, 64108, USA.
4
School of Medicine, University of Missouri-Kansas City, Kansas City, MO, 64108, USA.
5
Deparment of Pediatrics, and Clinical Translational Science Center, University of New Mexico Health Science Center, Albuquerque, NM, 87131, USA.
6
Edico Genome, Inc., 3344 North Torrey Pines Court, Plaza Level, La Jolla, CA, 92037, USA.
7
Center for Pediatric Genomic Medicine, Children's Mercy, 2401 Gilham Road, Kansas City, MO, 64108, USA. skingsmore@rchsd.org.
8
Department of Pediatrics, Children's Mercy, Kansas City, MO, 64108, USA. skingsmore@rchsd.org.
9
Department of Pathology, Children's Mercy, Kansas City, MO, 64108, USA. skingsmore@rchsd.org.
10
School of Medicine, University of Missouri-Kansas City, Kansas City, MO, 64108, USA. skingsmore@rchsd.org.
11
Rady Pediatric Genomics and Systems Medicine Institute, Rady Chlildren's Hospital, 3020 Children's Way, San Diego, CA, 92123, USA. skingsmore@rchsd.org.

Abstract

While the cost of whole genome sequencing (WGS) is approaching the realm of routine medical tests, it remains too tardy to help guide the management of many acute medical conditions. Rapid WGS is imperative in light of growing evidence of its utility in acute care, such as in diagnosis of genetic diseases in very ill infants, and genotype-guided choice of chemotherapy at cancer relapse. In such situations, delayed, empiric, or phenotype-based clinical decisions may meet with substantial morbidity or mortality. We previously described a rapid WGS method, STATseq, with a sensitivity of >96 % for nucleotide variants that allowed a provisional diagnosis of a genetic disease in 50 h. Here improvements in sequencing run time, read alignment, and variant calling are described that enable 26-h time to provisional molecular diagnosis with >99.5 % sensitivity and specificity of genotypes. STATseq appears to be an appropriate strategy for acutely ill patients with potentially actionable genetic diseases.

PMID:
26419432
PMCID:
PMC4588251
DOI:
10.1186/s13073-015-0221-8
[Indexed for MEDLINE]
Free PMC Article

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