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

Author

Listed:
  • Mallory J. Owen

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital)

  • Sebastien Lefebvre

    (Alexion Pharmaceuticals, Inc.)

  • Christian Hansen

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital)

  • Chris M. Kunard

    (Illumina, Inc.)

  • David P. Dimmock

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital
    Keck Graduate Institute)

  • 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
    University of California San Diego)

  • Mary J. Willis

    (Rady Children’s Institute for Genomic Medicine)

  • Annette Feigenbaum

    (Rady Children’s Hospital
    University of California San Diego)

  • Anna-Kaisa Niemi

    (Rady Children’s Hospital
    University of California San Diego)

  • Yan Ding

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital)

  • Luca Kraan

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital)

  • Katarzyna Ellsworth

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital)

  • Lucia Guidugli

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital)

  • 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
    Rady Children’s Hospital)

  • Yong H. Kwon

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital)

  • Zhanyang Zhu

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital)

  • Sergey Batalov

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital)

  • Shimul Chowdhury

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital
    Keck Graduate Institute)

  • Seema Rego

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital)

  • James Perry

    (Rady Children’s Hospital
    University of California San Diego)

  • Mark Speziale

    (Rady Children’s Hospital
    University of California San Diego)

  • Mark Nespeca

    (Rady Children’s Hospital
    University of California San Diego
    University of California San Diego)

  • Meredith S. Wright

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital
    Keck Graduate Institute)

  • 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
    Rady Children’s Hospital
    University of California San Diego)

  • Sheldon Gilmer

    (Rady Children’s Hospital)

  • Gail Knight

    (Rady Children’s Hospital
    University of California San Diego)

  • Albert Oriol

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital)

  • Jerica Lenberg

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital
    Keck Graduate Institute)

  • Shareef A. Nahas

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital)

  • Kate Perofsky

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital
    University of California San Diego)

  • Kyu Kim

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital
    University of California San Diego)

  • Jeanne Carroll

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital
    University of California San Diego)

  • Nicole G. Coufal

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital
    University of California San Diego)

  • Erica Sanford

    (Rady Children’s Institute for Genomic Medicine)

  • Kristen Wigby

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital
    University of California San Diego)

  • 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
    Rady Children’s Hospital)

  • Stephen F. Kingsmore

    (Rady Children’s Institute for Genomic Medicine
    Rady Children’s Hospital
    Keck Graduate Institute)

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.

Suggested Citation

  • 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 Nie, 2022. "An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31446-6
    DOI: 10.1038/s41467-022-31446-6
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    References listed on IDEAS

    as
    1. Ernest Turro & William J. Astle & Karyn Megy & Stefan Gräf & Daniel Greene & Olga Shamardina & Hana Lango Allen & Alba Sanchis-Juan & Mattia Frontini & Chantal Thys & Jonathan Stephens & Rutendo Mapet, 2020. "Whole-genome sequencing of patients with rare diseases in a national health system," Nature, Nature, vol. 583(7814), pages 96-102, July.
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