fix(science): stop scoring evidence that was never looked up
A review of the ranking's arithmetic found four things wrong, all of which made the score look better informed than it was. Measurements below are from this repo, not estimates. **Components now abstain instead of inventing a number.** A run without a VEP cache returns no allele frequencies, and rarity_score(None) read that as "absent from gnomAD, therefore maximally rare" and awarded every variant a free 0.25. jobs.has_frequencies / has_effect_scores record what the run actually produced, absent components are dropped from the weighted mean, and the remaining weights are renormalised so the score keeps its meaning. The UI shows "not looked up" rather than a bar, and the funnel stops calling a step "rare" when nothing was filtered. **Allele frequency is no longer a model feature.** It dominated: the same missense variant scored 0.887 at AF 0 and 0.0003 at AF 0.01. That double- counted, because the ranking already scores frequency explicitly, putting ~45% of every rank on one measurement; and it was circular, because ACMG assigns ClinVar's benign labels using frequency (BA1/BS1). Retraining without it moves missense AUROC from 0.872 to 0.500 — exactly random. The old figure was allele frequency, not variant-effect knowledge. The model therefore abstains unless CADD or AlphaMissense is present, since otherwise it only restates the consequence class. **Phenotype matching is weighted by information content** and HPO annotations are propagated up the ontology. Counting terms alike let "global developmental delay" (IC 0.93) count as much as "dilated left subclavian artery" (IC 7.88). **A real bug in the propagation, found by checking it.** The ancestor walk read a pre-order DFS backwards, which on a DAG lets a term resolve before one of its parents and inherit that parent alone instead of its lineage. It dropped 399 terms out of the phenotype branch, Camptodactyly and Chiari malformation among them. Now a true post-order, tested against a reference transitive closure. The ontology arithmetic moved to rarelens_ml.hpo so it is covered by tests, and rarelens_ml.benchmark measures the whole thing: across 10,178 published cases the causal gene ranks first 45.9-81.0% of the time against 5,269 genes, versus 0.02% for chance. docs/data.md reports that with its contamination (HPO's annotations come from these same case reports), and includes the measurement showing information-content weighting earns its place while propagation does not - kept anyway, for a reason the docs argue rather than assume.
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@@ -89,8 +89,22 @@ make training-set # a ClinVar-derived training table, ~370k labelled variants
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make train # fits, reports held-out metrics by gene split, moves the production alias
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```
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What those metrics do and do not mean is in [docs/data.md](docs/data.md); the headline AUROC
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flatters a model whose strongest feature is the consequence class.
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What those metrics do and do not mean is in [docs/data.md](docs/data.md). The short version:
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with allele frequency removed as a feature, the model scores AUROC **0.500 — exactly random — on
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missense variants**, because nothing is left but the consequence class the ranking already uses.
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It therefore abstains from the ranking unless CADD or AlphaMissense scores are available. The
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frequency feature is what made the old 0.872 look respectable, and ACMG assigns ClinVar's benign
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labels using frequency, so the feature had partly caused the label.
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```bash
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make benchmark # rank every published case in Phenopacket Store by phenotype alone
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```
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Across 10,178 published cases the causal gene is ranked first 45.9-81.0% of the time (the range is
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ties; random would be 0.02%). That benchmark is contaminated — HPO's gene annotations come from the
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same case reports — so read it as an upper bound. [docs/data.md](docs/data.md) has the full table,
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including the measurement that says information-content weighting earns its place and ontology
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propagation does not.
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Local Kubernetes: `make kind` builds the images, loads them into a kind cluster and applies
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`infra/k8s/overlays/local`.
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