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DNA and genomes · Use case

Assess somatic small-variant oncogenicity

Which methods help classify somatic SNVs and small indels while preserving uncertainty and the relevant gene mechanism?

Evidence collection plan

Collection planned

Evidence collection is planned for this question. The plan defines a comparison to investigate; it does not establish model performance or suitability.

Comparison question

Does a proposed method improve independent oncogenicity classification or review efficiency over explicit conventional criteria while retaining calibrated unresolved results?

Baselines to include

  • ClinGen/CGC/VICC criteria-based review under a pinned specification
  • A relevant specialised predictor assessed only within its actual output scope

Outcomes to measure

  • Category precision/recall and criteria fidelity
  • Calibration, abstention and unresolved-case coverage
  • Expert review effort, measured separately from treatment outcomes

Validation requirements

  • Use oncogenicity-specific labels with evidence, review status and dates.
  • Hold out allelic series, residues, studies and genes where unseen-gene transfer is intended.
  • Audit training and assertion overlap, including predictor contributions to labels.
  • Preserve tumour, assay and gene-mechanism context.
  • Use independent qualified somatic-variant adjudication and justified negative or uncertain examples.

Next collection task

Assemble a provenance table of oncogenicity assertions and orthogonal functional studies, including label-leakage exclusions and independently reviewable uncertain examples.

Your decision and inputs

Choose methods that support evidence-based oncogenicity review of somatic small variants and identify when the available evidence remains insufficient.

Who this is for
Somatic variant curators; Molecular pathologists evaluating interpretation methods
Context
Clinical research
Inputs
  • Variant, genome build, transcript, allele fraction, quality and confidence in somatic origin
  • Tumour context, gene mechanism and dated oncogenicity-specific assertions
  • Functional studies and the applicable criteria specification
Expected output
An oncogenicity classification or unresolved assessment with constituent criteria, conflicting findings and evidence needs.
Biological setting
SNVs and small indels, with separate protocols for oncogene missense and tumour-suppressor loss-of-function mechanisms.

Outside this use case

  • Inherited predisposition, fusions, rearrangements and copy-number variants require separate interpretation protocols.
  • Oncogenicity and molecular activity do not establish drug response or clinical actionability.
  • Germline-benign labels are not automatically valid somatic negative controls.

What this establishes for clinical research

Clinical research on somatic interpretation support. Tumour-only sequencing does not establish somatic origin, and therapeutic relevance needs a separate context-specific review.

Which evaluations inform this question?

No model comparison has been collected for this question yet.

Relevant methods and studies may exist outside this collection.

View the evidence plan and next collection task

What evidence is still missing?

  • Independent oncogenicity assertions and orthogonal functional evidence remain to be assembled with uncertain and negative examples.
  • Qualified somatic reviewers are needed to adjudicate criteria and evidence separately from the method being tested.
  • Older functional datasets and curated assertions may overlap model training or include predictor-derived evidence.

Contribute evidence or propose a correction

Sources and review

Automated source review · 2026-09-28 · Codex

Automated review of Rewire's workflow definition and sourced research brief against the agreed exploration and backlog. No human expert approval, model-applicability assessment or clinical validation is claimed.

Release provenance and downloads

Release 2026-09-28-c7b5ac6d34f2

Use-case input digest a0dd27a5f430ec387d309fd6e8615083250873ce4cff5e882c6fb8458ef80e95

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Question use-case-somatic-small-variant-oncogenicity. Any numerical results on this page come from this release's existing evaluation records.