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VarFish: comprehensive DNA variant analysis for diagnostics and research
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Definition & Maintenance of IVD Sub-Panels within VarFish #528

Closed your-highness closed 7 months ago

your-highness commented 2 years ago

Is your feature request related to a problem? Please describe. As opposed to phenotype/pathogenicity-prediction-based filtering done in many academic studies of germline variants, diagnostic tests in an ISO:15189-accredited / IVD-R-compliant diagnostic laboratory are "indication"-based In-vitro diagnostics (IVDs), i.e. clincians seek the confirmation of a clinical diagnosis. IVDs are scientifically / medically curated and validated relevant genes for a defined indication. Together these genes form so called "sub-panels" that are "fixed" after validation unless being re-evaluated and -validated (usually ~1 p.a.). To use VarFish for IVDs it is required to host an interface for the definition of IVDs, i.e. technical sub-panels defining a list of gene / transcript identifiers. This enables the strict (in the sense of "only") selection for sub-panel genes prior to any other step in the variant filtration / prioritization.

Describe the solution you'd like Here's a small breakdown of the tasks I can imagine:

  1. A backend to define technical IVD sub-panels, e.g. list of ENST or HGNC gene symbols via JSON / TXT.
  2. A user-interface to show all defined IVDs and their genes (inkl. size, comments) to all users.
  3. A user-interface to edit (incl. add) IVDs by authorized users, e.g. project owners / contributors.
  4. Versioning of IVDs, i.e. changes are documented
  5. A possibility to ingest also defined IVDs for cases when importing variant calling results, i.e. cases can be assign to IVDs in the data base.

I recommend using the term "IVD" as a label.

Describe alternatives you've considered Currently, filtering for variants in subpanel's genes can be facilitated via in the More.../Gene Lists & Regions/Gene Allowlist. However this approach is error-prone due to typeos and inconsistencies gene / transcript ids.

The feature Add from GE PanelApp under More.../Gene Lists & Regions/Gene Allowlist implements functionality "1." already.

Features "2.-5." are currently missing and should be evaluated for development.

Additional context In addition to the variant filtration based on IVD genes, a technical assessment of the quality in those genes, e.g. coverage, number of variants, Ti/Tv, overlap & concordance with dbSNP. This should be reported in addition to the panel-wide quality metrics already implemented. See Discussion https://github.com/bihealth/varfish-server/discussions/529

your-highness commented 2 years ago

As discussed with @holtgrewe:

Features 2. - 5. need assessment from devs and estimated implementation time. Ideally they are backported to the Athenea release for IVD-R conform usage.