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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-015-0221-8) contains supplementary material, which is available to authorized users.
Highlights
Genomic medicine is a new discipline whereby an individual’s genome information is used to guide personal strategies for disease prevention, etiologic diagnosis, and therapeutic selection [1, 2]
A standard form requesting the primary signs and symptoms, past diagnostic testing results, differential diagnosis or candidate genes, pertinent family history, availability of biologic parents for enrollment, and whether rapid whole genome sequencing (WGS) would potentially affect treatment was submitted for immediate evaluation by a team of experts at the Center for Pediatric Genomic Medicine (CPGM) at CM-KC
Twenty-six-hour STATseq appears to be an appropriate strategy for acutely ill patients with potentially actionable genetic diseases
Summary
Genomic medicine is a new discipline whereby an individual’s genome information is used to guide personal strategies for disease prevention, etiologic diagnosis, and therapeutic selection [1, 2]. Despite its recent implementation into clinical care, genomic medicine is already transforming the diagnosis, molecular staging, prognostic determination, and management of patients with symptoms suggestive of genetic diseases, Mendelian disorders (those caused by defects in single genes) and recurrent cancers [3,4,5,6,7,8,9,10,11]. Genomic medicine is transformative in these applications because it rapidly and simultaneously tests most genes potentially relevant to that patient’s disease, largely irrespective of the clinician’s differential diagnosis list or detailed knowledge of all of the conditions being tested [6, 11] Fifty hours was the interval between receipt of a blood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
