학술논문
Clinically Responsive Genomic Analysis Pipelines: Elements to improve detection rate and efficiency
Document Type
Article
Author
Sundercombe, Samantha Leigh; Berbic, Marina; Evans, Carey-Anne; Cliffe, Corrina; Elakis, George; Temple, Suzanna E.L.; Selvanathan, Arthavan; Ewans, Lisa; Quayum, Nila; Nixon, Cheng-Yee; Dias, Kerith-Rae; Lang, Sarah; Richards, Anna; Goh, Shuxiang; Wilson, Meredith; Mowat, David; Sachdev, Rani; Sandaradura, Sarah; Walsh, Maie; Farrar, Michelle A.; Walsh, Rebecca; Fletcher, Janice; Kirk, Edwin P.; Teunisse, Guus M.; Schofield, Deborah; Buckley, Michael Francis; Zhu, Ying; Roscioli, Tony
Source
The Journal of Molecular Diagnostics; 20210101, Issue: Preprints
Subject
Language
ISSN
15251578
Abstract
Massively parallel sequencing has improved Mendelian diagnostic rates dramatically. The authors 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/genome sample integrity and prioritize gene variants in Mendelian disorders. Re-analysis 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 USD$844.34 per additional diagnosis. Recommendations for genomic analysis pipeline requirements are summarised. Clinically responsive bioinformatics pipeline improvements increase diagnostic sensitivity and increase cost effectiveness.