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bioRxiv · 10.64898/2026.08.30.748028

An annotation-overlap-flagged rare-disease gene-prioritisation benchmark and PMC index recipe

Angulo, J.·Yeste, V.·Espinos-Morato, H.
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Abstract

Benchmarks for rare-disease gene prioritisation are assembled from published clinical cases. Those cases often come from the same publications used to build knowledge-base ("curated") tools, so a curated tool can be scored on its own source literature. This resource makes that circularity measurable. We release a stratified benchmark of 1,047 rare-disease cases from the GA4GH Phenopacket Store v0.1.26. Each case pairs a Human Phenotype Ontology profile with a 50-gene candidate list (one causal gene, 49 distractors) and the causal-gene label, sampled across four operational MONDO-derived disease strata and issued in two case-paired variants: random distractors, and phenotype-similar distractors selected by HPO Resnik similarity. Two case-level metadata layers support fairer evaluation: a per-case flag recording whether a case's source publication is cited in the HPO disease-annotation file, defining an overlap-absent subset (n = 282), and publication-recency strata. We also specify a deterministic, version-pinned recipe for a hybrid dense-plus-sparse retrieval index over approximately 2.25 million PMC Open Access articles (52,777,395 chunks). The resource reports no tool comparisons.

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Angulo, J., Yeste, V., Espinos-Morato, H.. 2026-09-03. An annotation-overlap-flagged rare-disease gene-prioritisation benchmark and PMC index recipe. https://doi.org/10.64898/2026.08.30.748028

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