PanelApp crowdsources expert knowledge to establish consensus diagnostic gene panels

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A fundamental problem in rare-disease diagnostics is the lack of consensus as to which genes have sufficient evidence to attribute causation. To address this issue, we have created PanelApp (https://panelapp.genomicsengland.co.uk), a publicly available knowledge base of curated virtual gene panels.

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Fig. 1
Fig. 2: PanelApp genome coverage.
Fig. 3
Fig. 4: PanelApp traffic-light system for evidence level.

Data availability

PanelApp is a publicly available database. The user interface can be found at https://panelapp.genomicsengland.co.uk/, and the API can be found at https://panelapp.genomicsengland.co.uk/api/docs/. The PanelApp software is available from https://github.com/genomicsengland/panelapp/.

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Acknowledgements

We thank all PanelApp reviewers and those who have contributed feedback or gene lists to help in the development of PanelApp; individual panels show the names and affiliations of contributors. We thank all participants in the 100,000 Genomes Project. We extend special thanks to the following contributors to PanelApp development, curation, documentation and outreach: R. Jones, A. Gardham, C. Wright, C. Boustred, K. McCaffrey, C. Campbell, J. Whittaker, C. Turnbull, M. Ryten, A. Devereau, T. Fowler, Members of the E&I GeCIP Domain (S. Ellard, S. Abbs, D. McCullun, H. Firth and W. Newman), V. Fryer, C. Johnson, J. Carroll, E. Ivanov, P. Hayes, M. Athanasopoulou, L. Carr, L. Dinh, A. Sosinsky, M. Parker, L. Hawkes, and J. Deller; and to M. Child for critical reading of the manuscript. M. Caulfield was funded by the National Institute for Health Research (NIHR) as part of the portfolio of translational research of the NIHR Biomedical Research Center at Barts and The London School of Medicine and Dentistry. He is supported as an NIHR senior investigator, and this work was funded by the MRC eMedLab award. This research was made possible through access to the data and findings generated by the 100,000 Genomes Project. The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health). The 100,000 Genomes Project is funded by the NIHR and NHSE. The Wellcome Trust, Cancer Research UK and the Medical Research Council have also funded research infrastructure. The 100,000 Genomes Project uses data provided by patients and collected by the NHSE as part of their care and support.

Author information

A.R.M., E.M.M. and A.R. conceived PanelApp, and all authors contributed substantially to the project. E.M.M., A.R.M. and E.W. planned and wrote the manuscript, which was edited and contributed to by R.E.F., S.L., L.C.D., O.N., I.U.S.L., K.R.S., O.G., E.H., E.T., R.H.S., E.B., A.T., H.B., A.d.B., K.I., D.K., D.S., A.R. and M.C.

Correspondence to Ellen M. McDonagh.

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Competing interests

The authors declare no competing interests.

Extended data

Extended Data Fig. 1 Reviews of genes in PanelApp over time.

The number of reviews on panels for the 100,000 Genomes Project from external reviewers (blue) and Genomics England curators (red) in PanelApp for each month. The peaks at November 2015, February 2016 and August 2017 are largely due to the import of many reviews to the Intellectual disability panel. The peak at December 2015 is due to the import of many reviews to the Hereditary neuropathy (Charcot Marie-Tooth) panel. The peak at November 2017 corresponds to the launch of PanelApp database release 2.0, with some reviews under this peak pre-dating this month.

Extended Data Fig. 2 Worldwide coverage of PanelApp Reviewers.

Map of the location of registered PanelApp external reviewers as of January 2019. The map was generated by extracting the country from PanelApp users’ workplace email addresses and plotting on a world map.

Extended Data Fig. 3 Profile of reviews for each current gene status.

For genes on version 1+ gene panels in the 100,000 Genomes Project, the current rating (green, amber, red, grey) is plotted on the x-axis. For each, the number of reviews from external reviewers (in January 2019) in which the reviewer rated the gene green, amber or red is plotted on the y-axis, demonstrating an overall consensus for the current rating. Genes are converted to grey by a Genomics England curator if reviews suggest that the gene should be removed from the panel, and the majority will be given a red rating by external reviewers.

Extended Data Fig. 4 Changes to gene panels after expert review and further curation for five example panels.

The number and rating (green/amber/red) of genes on the first (v0) and latest versions (as of January 2019, v1+) of five example panels in PanelApp. No overall changes to the two green genes in the classical tuberous sclerosis panel were made from version 0 to version 1; these are two well-established genes found on all source panels with a high level of evidence for disease-causation. For the intellectual disability panel, there was little consensus between the four original sources and therefore few green genes prior to external review. After external review and curation, the number of green genes expanded significantly (version 1 compared to version 0). A comprehensive update of the version 1 intellectual disability panel was subsequently undertaken, and due to a large number of additional green genes the panel was promoted to version 2. Continual updates to the panels are reflected in the minor version (for example 595 of the intellectual disability panel).

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Martin, A.R., Williams, E., Foulger, R.E. et al. PanelApp crowdsources expert knowledge to establish consensus diagnostic gene panels. Nat Genet 51, 1560–1565 (2019) doi:10.1038/s41588-019-0528-2

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