TY - JOUR
T1 - Clinically responsive genomic analysis pipelines
T2 - Elements to improve detection rate and efficiency
AU - Sundercombe, Samantha Leigh
AU - Berbic, Marina
AU - Evans, Carey-Anne
AU - Cliffe, Corrina
AU - Elakis, George
AU - Temple, Suzanna E. L.
AU - Selvanathan, Arthavan
AU - Ewans, Lisa
AU - Quayum, Nila
AU - Nixon, Cheng-Yee
AU - Dias, Kerith-Rae
AU - Lang, Sarah
AU - Richards, Anna
AU - Goh, Shuxiang
AU - Wilson, Meredith
AU - Mowat, David
AU - Sachdev, Rani
AU - Sandaradura, Sarah
AU - Walsh, Maie
AU - Farrar, Michelle A
AU - Walsh, Rebecca
AU - Fletcher, Janice
AU - Kirk, Edwin P
AU - Teunisse, Guus M.
AU - Schofield, Deborah
AU - Buckley, Michael Francis
AU - Zhu, Ying
AU - Roscioli, Tony
N1 - Copyright © 2021. Published by Elsevier Inc.
PY - 2021/7
Y1 - 2021/7
N2 - Massively parallel sequencing has markedly improved mendelian diagnostic rates. This study assessed the effects of custom alterations to a diagnostic genomic bioinformatic pipeline in response to clinical need and derived practice recommendations relative to diagnostic rates and efficiency. The Genomic Annotation and Interpretation Application (GAIA) bioinformatics pipeline was designed to detect panel, exome, and genome sample integrity and prioritize gene variants in mendelian disorders. Reanalysis of selected negative cases was performed after improvements to the pipeline. GAIA improvements and their effect on sensitivity are described, including addition of a PubMed search for gene-disease associations not in the Online Mendelian Inheritance of Man database, inclusion of a process for calling low-quality variants (known as QPatch), and gene symbol nomenclature consistency checking. The new pipeline increased the diagnostic rate and reduced staff costs, resulting in a saving of US$844.34 per additional diagnosis. Recommendations for genomic analysis pipeline requirements are summarized. Clinically responsive bioinformatics pipeline improvements increase diagnostic sensitivity and increase cost-effectiveness.
AB - Massively parallel sequencing has markedly improved mendelian diagnostic rates. This study assessed the effects of custom alterations to a diagnostic genomic bioinformatic pipeline in response to clinical need and derived practice recommendations relative to diagnostic rates and efficiency. The Genomic Annotation and Interpretation Application (GAIA) bioinformatics pipeline was designed to detect panel, exome, and genome sample integrity and prioritize gene variants in mendelian disorders. Reanalysis of selected negative cases was performed after improvements to the pipeline. GAIA improvements and their effect on sensitivity are described, including addition of a PubMed search for gene-disease associations not in the Online Mendelian Inheritance of Man database, inclusion of a process for calling low-quality variants (known as QPatch), and gene symbol nomenclature consistency checking. The new pipeline increased the diagnostic rate and reduced staff costs, resulting in a saving of US$844.34 per additional diagnosis. Recommendations for genomic analysis pipeline requirements are summarized. Clinically responsive bioinformatics pipeline improvements increase diagnostic sensitivity and increase cost-effectiveness.
UR - http://www.scopus.com/inward/record.url?scp=85109084615&partnerID=8YFLogxK
U2 - 10.1016/j.jmoldx.2021.04.007
DO - 10.1016/j.jmoldx.2021.04.007
M3 - Article
C2 - 33962052
SN - 1525-1578
VL - 23
SP - 894
EP - 905
JO - Journal of Molecular Diagnostics
JF - Journal of Molecular Diagnostics
IS - 7
ER -