학술논문
An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases
Document Type
Original Paper
Author
Owen, Mallory J.; Lefebvre, Sebastien; Hansen, Christian; Kunard, Chris M.; Dimmock, David P.; Smith, Laurie D.; Scharer, Gunter; Mardach, Rebecca; Willis, Mary J.; Feigenbaum, Annette; Niemi, Anna-Kaisa; Ding, Yan; Van Der Kraan, Luca; Ellsworth, Katarzyna; Guidugli, Lucia; Lajoie, Bryan R.; McPhail, Timothy K.; Mehtalia, Shyamal S.; Chau, Kevin K.; Kwon, Yong H.; Zhu, Zhanyang; Batalov, Sergey; Chowdhury, Shimul; Rego, Seema; Perry, James; Speziale, Mark; Nespeca, Mark; Wright, Meredith S.; Reese, Martin G.; De La Vega, Francisco M.; Azure, Joe; Frise, Erwin; Rigby, Charlene Son; White, Sandy; Hobbs, Charlotte A.; Gilmer, Sheldon; Knight, Gail; Oriol, Albert; Lenberg, Jerica; Nahas, Shareef A.; Perofsky, Kate; Kim, Kyu; Carroll, Jeanne; Coufal, Nicole G.; Sanford, Erica; Wigby, Kristen; Weir, Jacqueline; Thomson, Vicki S.; Fraser, Louise; Lazare, Seka S.; Shin, Yoon H.; Grunenwald, Haiying; Lee, Richard; Jones, David; Tran, Duke; Gross, Andrew; Daigle, Patrick; Case, Anne; Lue, Marisa; Richardson, James A.; Reynders, John; Defay, Thomas; Hall, Kevin P.; Veeraraghavan, Narayanan; Kingsmore, Stephen F.
Source
Nature Communications. 13(1)
Subject
Language
English
ISSN
2041-1723
Abstract
While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for genetic disease diagnosis and acute management guidance. Diagnosis is achieved in 13.5 h by expedited whole genome sequencing, with superior analytic performance for structural and copy number variants. An expert panel adjudicated the indications, contraindications, efficacy, and evidence-of-efficacy of 9911 drug, device, dietary, and surgical interventions for 563 severe, childhood, genetic diseases. The 421 (75%) diseases and 1527 (15%) effective interventions retained are integrated with 13 genetic disease information resources and appended to diagnostic reports (https://gtrx.radygenomiclab.com). This system provided correct diagnoses in four retrospectively and two prospectively tested infants. The Genome-to-Treatment system facilitates optimal outcomes in children with rapidly progressive genetic diseases.
Rapid diagnosis and implementation of treatments is crucial in many genetic conditions. Here the authors describe Genome-to-Treatment, a virtual disease management system that can achieve a rapid diagnosis by expedited whole genome sequencing in 13.5 hours and provide guidance to clinicians for possible therapies.
Rapid diagnosis and implementation of treatments is crucial in many genetic conditions. Here the authors describe Genome-to-Treatment, a virtual disease management system that can achieve a rapid diagnosis by expedited whole genome sequencing in 13.5 hours and provide guidance to clinicians for possible therapies.