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

作者：Miller Neil A; Farrow Emily G; Gibson Margaret; Willig Laurel K; Twist Greyson; Yoo Byunggil; Marrs Tyler; Corder Shane; Krivohlavek Lisa; Walter Adam; Petrikin Josh E; Saunders Carol J; Thiffault Isabelle; Soden Sarah E; Smith Laurie D; Dinwiddie Darrell L; Herd Suzanne; Cakici Julie A; Catreux Severine; Ruehle Mike; Kingsmore Stephen F^*

来源：Genome Medicine, 2015, 7(1): 100.

DOI：10.1186/s13073-015-0221-8

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.

• 出版日期2015-9-30