Scaling national and international improvement in virtual gene panel curation via a collaborative approach to discordance resolution

Zornitza Stark; Rebecca E Foulger; Eleanor Williams; Bryony A Thompson; Chirag Patel; Sebastian Lunke; Catherine Snow; Ivone U S Leong; Arina Puzriakova; Louise C Daugherty; Sarah Leigh; Christopher Boustred; Olivia Niblock; Antonio Rueda-Martin; Oleg Gerasimenko; Kevin Savage; William Bellamy; Victor San Kho Lin; Roman Valls; Lavinia Gordon; Helen K Brittain; Ellen R A Thomas; Ana Lisa Taylor Tavares; Meriel McEntagart; Susan M White; Tiong Y Tan; Alison Yeung; Lilian Downie; Ivan Macciocca; Elena Savva; Crystle Lee; Ain Roesley; Paul De Fazio; Jane Deller; Zandra C Deans; Sue L Hill; Mark J Caulfield; Kathryn N North; Richard H Scott; Augusto Rendon; Oliver Hofmann; Ellen M McDonagh

doi:10.1016/j.ajhg.2021.06.020

Scaling national and international improvement in virtual gene panel curation via a collaborative approach to discordance resolution

Am J Hum Genet. 2021 Sep 2;108(9):1551-1557. doi: 10.1016/j.ajhg.2021.06.020. Epub 2021 Jul 29.

Authors

Zornitza Stark¹, Rebecca E Foulger², Eleanor Williams², Bryony A Thompson³, Chirag Patel⁴, Sebastian Lunke⁵, Catherine Snow², Ivone U S Leong², Arina Puzriakova², Louise C Daugherty², Sarah Leigh², Christopher Boustred², Olivia Niblock², Antonio Rueda-Martin², Oleg Gerasimenko², Kevin Savage², William Bellamy², Victor San Kho Lin⁶, Roman Valls⁶, Lavinia Gordon⁶, Helen K Brittain², Ellen R A Thomas⁷, Ana Lisa Taylor Tavares², Meriel McEntagart⁸, Susan M White⁵, Tiong Y Tan⁵, Alison Yeung⁵, Lilian Downie⁹, Ivan Macciocca¹⁰, Elena Savva¹⁰, Crystle Lee¹⁰, Ain Roesley¹⁰, Paul De Fazio¹⁰, Jane Deller¹¹, Zandra C Deans¹¹, Sue L Hill¹¹, Mark J Caulfield², Kathryn N North¹², Richard H Scott², Augusto Rendon², Oliver Hofmann⁶, Ellen M McDonagh¹³

Affiliations

¹ Australian Genomics Health Alliance, Melbourne, VIC 3052, Australia; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia; University of Melbourne, Melbourne, VIC 3010, Australia. Electronic address: [email protected].
² Genomics England, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
³ University of Melbourne, Melbourne, VIC 3010, Australia; Royal Melbourne Hospital, Melbourne, VIC 3050, Australia.
⁴ Genetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, QLD 4006, Australia.
⁵ Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia; University of Melbourne, Melbourne, VIC 3010, Australia.
⁶ Centre for Cancer Research, University of Melbourne, Victorian Comprehensive Cancer Centre, Melbourne, VIC 3000, Australia.
⁷ Genomics England, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK; Guy's and St Thomas's NHS Trust, London SE1 9RS, UK.
⁸ Genomics England, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK; St George's University Hospitals NHS Trust, London SW17 0QT, UK.
⁹ University of Melbourne, Melbourne, VIC 3010, Australia; Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia.
¹⁰ Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia.
¹¹ National Health Service England and National Health Service Improvement, London SE1 6LH, UK.
¹² Australian Genomics Health Alliance, Melbourne, VIC 3052, Australia; University of Melbourne, Melbourne, VIC 3010, Australia; Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia.
¹³ Genomics England, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK; Open Targets and European Molecular Biology Laboratory - European Bioinformatics Institute, Wellcome Genome Campus, Hinxton CB10 1SD, UK.

Abstract

Clinical validity assessments of gene-disease associations underpin analysis and reporting in diagnostic genomics, and yet wide variability exists in practice, particularly in use of these assessments for virtual gene panel design and maintenance. Harmonization efforts are hampered by the lack of agreed terminology, agreed gene curation standards, and platforms that can be used to identify and resolve discrepancies at scale. We undertook a systematic comparison of the content of 80 virtual gene panels used in two healthcare systems by multiple diagnostic providers in the United Kingdom and Australia. The process was enabled by a shared curation platform, PanelApp, and resulted in the identification and review of 2,144 discordant gene ratings, demonstrating the utility of sharing structured gene-disease validity assessments and collaborative discordance resolution in establishing national and international consensus.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Australia
Biomarkers / metabolism
Consensus*
Data Curation / methods
Data Curation / standards*
Delivery of Health Care
Gene Expression
Gene Ontology
Genetic Diseases, Inborn / diagnosis
Genetic Diseases, Inborn / genetics*
Genetic Diseases, Inborn / pathology
Genomics / methods
Genomics / standards*
Humans
Mobile Applications / supply & distribution
Molecular Sequence Annotation / standards*
Terminology as Topic
United Kingdom

Substances

Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding