An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases

Mallory J. Owen, Sebastien Lefebvre, Christian Hansen, Chris M. Kunard, David P. Dimmock, Laurie D. Smith, Gunter Scharer, Rebecca Mardach, Mary J. Willis, Annette Feigenbaum, Anna-Kaisa Niemi, Yan Ding, Luca Kraan, Katarzyna Ellsworth, Lucia Guidugli, Bryan R. Lajoie, Timothy K. McPhail, Shyamal S. Mehtalia, Kevin K. Chau, Yong H. Kwon, Zhanyang Zhu, Sergey Batalov, Shimul Chowdhury, Seema Rego, James Perry, Mark Speziale, Mark Nespeca, Meredith S. Wright, Martin G. Reese, Francisco M. Vega, Joe Azure, Erwin Frise, Charlene Son Rigby, Sandy White, Charlotte A. Hobbs, Sheldon Gilmer, Gail Knight, Albert Oriol, Jerica Lenberg, Shareef A. Nahas, Kate Perofsky, Kyu Kim, Jeanne Carroll, Nicole G. Coufal, Erica Sanford, Kristen Wigby, Jacqueline Weir, Vicki S. Thomson, Louise Fraser, Seka S. Lazare, Yoon H. Shin, Haiying Grunenwald, Richard Lee, David Jones, Duke Tran, Andrew Gross, Patrick Daigle, Anne Case, Marisa Lue, James A. Richardson, John Reynders, Thomas Defay, Kevin P. Hall, Narayanan Veeraraghavan and Stephen F. Kingsmore ()
Additional contact information
Mallory J. Owen: Rady Children’s Institute for Genomic Medicine
Sebastien Lefebvre: Alexion Pharmaceuticals, Inc.
Christian Hansen: Rady Children’s Institute for Genomic Medicine
Chris M. Kunard: Illumina, Inc.
David P. Dimmock: Rady Children’s Institute for Genomic Medicine
Laurie D. Smith: Rady Children’s Institute for Genomic Medicine
Gunter Scharer: Rady Children’s Institute for Genomic Medicine
Rebecca Mardach: Rady Children’s Hospital
Mary J. Willis: Rady Children’s Institute for Genomic Medicine
Annette Feigenbaum: Rady Children’s Hospital
Anna-Kaisa Niemi: Rady Children’s Hospital
Yan Ding: Rady Children’s Institute for Genomic Medicine
Luca Kraan: Rady Children’s Institute for Genomic Medicine
Katarzyna Ellsworth: Rady Children’s Institute for Genomic Medicine
Lucia Guidugli: Rady Children’s Institute for Genomic Medicine
Bryan R. Lajoie: Illumina, Inc.
Timothy K. McPhail: Illumina, Inc.
Shyamal S. Mehtalia: Illumina, Inc.
Kevin K. Chau: Rady Children’s Institute for Genomic Medicine
Yong H. Kwon: Rady Children’s Institute for Genomic Medicine
Zhanyang Zhu: Rady Children’s Institute for Genomic Medicine
Sergey Batalov: Rady Children’s Institute for Genomic Medicine
Shimul Chowdhury: Rady Children’s Institute for Genomic Medicine
Seema Rego: Rady Children’s Institute for Genomic Medicine
James Perry: Rady Children’s Hospital
Mark Speziale: Rady Children’s Hospital
Mark Nespeca: Rady Children’s Hospital
Meredith S. Wright: Rady Children’s Institute for Genomic Medicine
Martin G. Reese: Fabric Genomics, Inc.
Francisco M. Vega: Fabric Genomics, Inc.
Joe Azure: Fabric Genomics, Inc.
Erwin Frise: Fabric Genomics, Inc.
Charlene Son Rigby: Fabric Genomics, Inc.
Sandy White: Fabric Genomics, Inc.
Charlotte A. Hobbs: Rady Children’s Institute for Genomic Medicine
Sheldon Gilmer: Rady Children’s Hospital
Gail Knight: Rady Children’s Hospital
Albert Oriol: Rady Children’s Institute for Genomic Medicine
Jerica Lenberg: Rady Children’s Institute for Genomic Medicine
Shareef A. Nahas: Rady Children’s Institute for Genomic Medicine
Kate Perofsky: Rady Children’s Institute for Genomic Medicine
Kyu Kim: Rady Children’s Institute for Genomic Medicine
Jeanne Carroll: Rady Children’s Institute for Genomic Medicine
Nicole G. Coufal: Rady Children’s Institute for Genomic Medicine
Erica Sanford: Rady Children’s Institute for Genomic Medicine
Kristen Wigby: Rady Children’s Institute for Genomic Medicine
Jacqueline Weir: Illumina, Inc.
Vicki S. Thomson: Illumina, Inc.
Louise Fraser: Illumina, Inc.
Seka S. Lazare: Illumina, Inc.
Yoon H. Shin: Illumina, Inc.
Haiying Grunenwald: Illumina, Inc.
Richard Lee: Illumina, Inc.
David Jones: Illumina, Inc.
Duke Tran: Illumina, Inc.
Andrew Gross: Illumina, Inc.
Patrick Daigle: Illumina, Inc.
Anne Case: Illumina, Inc.
Marisa Lue: Illumina, Inc.
James A. Richardson: Illumina, Inc.
John Reynders: Alexion Pharmaceuticals, Inc.
Thomas Defay: Alexion Pharmaceuticals, Inc.
Kevin P. Hall: Illumina, Inc.
Narayanan Veeraraghavan: Rady Children’s Institute for Genomic Medicine
Stephen F. Kingsmore: Rady Children’s Institute for Genomic Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31446-6

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DOI: 10.1038/s41467-022-31446-6

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