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DNA and genomes · Use case

Reanalyse unresolved rare-disease cases

Which reanalysis methods find new diagnoses or reduce review effort when given the same updated information?

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 reanalysis method improve confirmed diagnoses or reduce review burden relative to refreshed conventional analysis using identical updated knowledge, phenotypes and calls?

Baselines to include

  • Refreshed conventional analysis with the same updated information
  • The original unresolved cohort for programme-level incremental yield, reported separately

Outcomes to measure

  • New confirmed diagnoses per eligible case over a stated interval
  • Added method benefit under equal updated inputs
  • False alerts, review time and the reason for each resolved case

Validation requirements

  • Record original and update dates; exclude future knowledge at each analysis time.
  • Separate benefit from new information, calling changes and prioritisation changes.
  • Audit family/site overlap and originating-laboratory label circularity.
  • Count diagnoses and diagnosed individuals separately; distinguish first and repeated cycles.
  • Use independent qualified clinical-genetics review to confirm outcomes.

Next collection task

Create a dated reanalysis evidence table with separate programme-yield and method-comparison columns, noting where an equal-input comparator is missing.

Your decision and inputs

Choose a workflow that identifies previously unresolved cases worth reopening and explains the evidence changes that warrant review.

Who this is for
Clinical genomics services responsible for unresolved cases; Laboratory reanalysis leads
Context
Clinical research
Inputs
  • Original ES/GS calls, coverage, report, filters and analysis date
  • Updated phenotype, pedigree and gene–disease or variant evidence
  • Dated changes to calling and interpretation methods
Expected output
A prioritised queue of new or changed findings, their evidence history and the review or confirmation needed to resolve each case.
Biological setting
A defined cohort remaining unresolved after an earlier ES/GS analysis, followed over a stated interval. Variant reevaluation and whole-case reanalysis are recorded separately.

Outside this use case

  • Reranking known solved cases does not establish new diagnostic yield.
  • New knowledge, phenotypes or variant calls must not be counted automatically as algorithmic improvement.
  • A changed database label or new candidate is not a confirmed diagnosis.

What this establishes for clinical research

Clinical research on reanalysis support. Programme-level yield and the added value of a method require different comparisons; diagnoses and diagnosed individuals have separate denominators.

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?

  • Dated programme outcomes and comparisons against refreshed conventional analysis remain to be collected.
  • Independent qualified review must confirm new findings and investigate false alerts or retracted diagnoses.
  • Published implementation evidence does not establish a universal reanalysis interval or access to controlled cohorts.

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-unresolved-rare-disease-reanalysis. Any numerical results on this page come from this release's existing evaluation records.