Clinically responsive genomic analysis pipelines: Elements to improve detection rate and efficiency

Samantha Leigh Sundercombe, Marina Berbic, Carey-Anne Evans, Corrina Cliffe, George Elakis, Suzanna E. L. Temple, Arthavan Selvanathan, Lisa Ewans, Nila Quayum, Cheng-Yee Nixon, Kerith-Rae Dias, Sarah Lang, Anna Richards, Shuxiang Goh, Meredith Wilson, David Mowat, Rani Sachdev, Sarah Sandaradura, Maie Walsh, Michelle A FarrarRebecca Walsh, Janice Fletcher, Edwin P Kirk, Guus M. Teunisse, Deborah Schofield, Michael Francis Buckley, Ying Zhu, Tony Roscioli

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)894-905
Number of pages12
JournalJournal of Molecular Diagnostics
Issue number7
Early online date4 May 2021
Publication statusPublished - Jul 2021


Dive into the research topics of 'Clinically responsive genomic analysis pipelines: Elements to improve detection rate and efficiency'. Together they form a unique fingerprint.

Cite this