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DNA and genomes · Use case

Select regulatory variants and genes for functional follow-up

Which variants, regulatory elements and genes should I perturb to explain a disease-associated locus?

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 method select more experimentally supported regulatory hypotheses than compatible distance or linking baselines at the same follow-up budget?

Baselines to include

  • Distance-based variant/gene or enhancer/gene selection where applicable
  • ABC, ENCODE-rE2G or scE2G for compatible element–gene linking tasks
  • Sequence predictors compared only on the allele-effect outputs they produce

Outcomes to measure

  • Allele-dependent regulatory effects
  • Endogenous element–gene and allele–gene effects, measured separately
  • Confirmed follow-up hits per assay budget

Validation requirements

  • Define the allele-effect, linking or selection endpoint before choosing a comparison.
  • Hold out loci and studies; audit linkage-disequilibrium and pretraining overlap.
  • Preserve cell context, genome build, assay and perturbation type.
  • Keep reporter activity, whole-element perturbation, single-base effects and disease causality distinct.

Next collection task

Build separate extraction tables for CRISPRi linking, allele-specific reporter and endogenous-editing studies, identifying which test experimental selection.

Your decision and inputs

Choose allele edits, regulatory-element perturbations and gene readouts that can distinguish competing explanations for a locus.

Who this is for
Functional geneticists; Researchers interpreting disease-associated loci
Context
Research
Inputs
  • Fine-mapped variants with genome build, ancestry and linkage-disequilibrium context
  • Candidate regulatory elements, genes and a relevant cell type
  • Sequence and available chromatin, expression or contact measurements
  • The feasible perturbation assay, readout and follow-up budget
Expected output
A prioritised set of variant–element–gene hypotheses, with the experiments needed to test each link and effect direction where supported.
Biological setting
Research follow-up of defined disease-associated loci in a specified cell system. Allele-effect prediction, element–gene linking and experimental shortlist selection are separate comparisons.

Outside this use case

  • Reporter activity does not by itself establish endogenous regulation.
  • Perturbing an entire regulatory element is different from editing one allele.
  • A regulatory link alone does not establish a gene’s causal role in disease.

What this establishes for clinical research

Research only. Molecular effects and regulatory links do not establish clinical variant classification or diagnostic validity.

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?

  • Endpoint-specific comparisons must be collected for allele effects, element–gene links and experimental selection.
  • Evidence from the intended cell context and endogenous perturbation may be missing even when reporter or linking benchmarks exist.
  • Human domain review remains unassigned.

Contribute evidence or propose a correction

Sources and review

Automated source review · 2026-09-28 · Codex

Automated review of the workflow definition, cited primary-source scope and collection plan. No model evaluation or applicability mapping was added. Human domain review remains unassigned.

Release provenance and downloads

Release 2026-09-28-c7b5ac6d34f2

Use-case input digest a0dd27a5f430ec387d309fd6e8615083250873ce4cff5e882c6fb8458ef80e95

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Question use-case-regulatory-variant-gene-follow-up. Any numerical results on this page come from this release's existing evaluation records.