A semiautomated whole-exome sequencing workflow leads to increased diagnostic yield and identification of novel candidate variants

Jianling Ji; Lishuang Shen; Moiz Bootwalla; Catherine Quindipan; Tatiana Tatarinova; Dennis T Maglinte; Jonathan Buckley; Gordana Raca; Sulagna C Saitta; Jaclyn A Biegel; Xiaowu Gai

doi:10.1101/mcs.a003756

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A semiautomated whole-exome sequencing workflow leads to increased diagnostic yield and identification of novel candidate variants

Journal article

Open access

Peer reviewed

A semiautomated whole-exome sequencing workflow leads to increased diagnostic yield and identification of novel candidate variants

Jianling Ji, Lishuang Shen, Moiz Bootwalla, Catherine Quindipan, Tatiana Tatarinova, Dennis T Maglinte, Jonathan Buckley, Gordana Raca, Sulagna C Saitta, Jaclyn A Biegel, …

Cold Spring Harbor molecular case studies, Vol.5(2), p.a003756

04/2019

DOI: https://doi.org/10.1101/mcs.a003756

PMCID: PMC6549575

PMID: 30755392

Abstract

Adolescent

Autism Spectrum Disorder - diagnosis

Autism Spectrum Disorder - genetics

Child

Child, Preschool

Early Diagnosis

Female

Genetic Predisposition to Disease

Humans

Immune System Diseases - diagnosis

Immune System Diseases - genetics

Infant

Infant, Newborn

Male

Neoplasms - diagnosis

Neoplasms - genetics

Sensitivity and Specificity

Time Factors

Whole Exome Sequencing - methods

Workflow

Young Adult

Advancing the clinical utility of whole-exome sequencing (WES) for patients with suspected genetic disorders is largely driven by bioinformatics approaches that streamline data processing and analysis. Herein, we describe our experience with implementing a semiautomated and phenotype-driven WES diagnostic workflow, incorporating both the DRAGEN pipeline and the Exomiser variant prioritization tool, at an academic children's hospital with an ethnically diverse pediatric patient population. We achieved a 41% molecular diagnostic rate for 66 duo-, quad-, or trio-WES cases, and 28% for 40 singleton-WES cases. Preliminary results were returned to ordering physicians within 1 wk for 12 of 38 (32%) probands with positive findings, which were instrumental in guiding the appropriate clinical management for a variety of patients, especially in critical care settings. The semiautomated and streamlined WES workflow also enabled us to identify novel variants in candidate disease genes in patients with developmental delay and autism and immune disorders and cancer, including , , , , , and Together, we demonstrated the implementation of a streamlined WES workflow that was successfully applied for both clinical and research purposes.

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Title: A semiautomated whole-exome sequencing workflow leads to increased diagnostic yield and identification of novel candidate variants
Creators: Jianling Ji - Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
Lishuang Shen - Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, California 90027, USA
Moiz Bootwalla - Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, California 90027, USA
Catherine Quindipan - Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, California 90027, USA
Tatiana Tatarinova - University of La Verne
Dennis T Maglinte - Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, California 90027, USA
Jonathan Buckley - Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
Gordana Raca - Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
Sulagna C Saitta - Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
Jaclyn A Biegel - Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
Xiaowu Gai - Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
Publication Details: Cold Spring Harbor molecular case studies, Vol.5(2), p.a003756
Identifiers: 991004106070906311
Academic Unit: Biology
Language: English
Resource Type: Journal article

A semiautomated whole-exome sequencing workflow leads to increased diagnostic yield and identification of novel candidate variants

Abstract

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