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bioRxiv · 10.64898/2026.06.11.731512

RepGene: Toward a Unified Gene Representation Space Robust to Missing Biological Views

Hou, H.·Xia, T.·Hu, L.·Qin, H.·Zhang, Y.·Li, Y.·Fang, S.·Cao, L.
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Abstract

This study evaluates how multi-view gene representations should be compared under a matched contract. Each of 18,460 genes is described by five aligned views: DNA sequence-derived features (D), RNA sequence-derived features (R), protein language-model embeddings (P), curated text knowledge (K), and single-cell expression (X). The contract fixes the gene universe, the 256-D output, label-free outer-training-only fitting, one random-forest probe, and task-equal Macro-F1 over nine registered binary tasks, and varies only the fusion operator across four protocol-defined input states: Core (DNA+RNA+protein), Core+K, Core+X, and Core+K+X. Under these states, the top-scoring operator changes with the available view combination and all task-bootstrap intervals overlap, establishing a condition-dependent rather than universal ranking pattern. An independently configured external RF track provides a separate check of the numerical range, while a gene-to-cell boundary diagnostic shows that gene-level differences attenuate toward a dimension-matched random control under expression-weighted aggregation, as predicted by a dilution identity. Historical log-derived multiplicative-interaction screening is retained only as magnitude-only supplementary evidence because fold-level records are unavailable. The contribution is therefore the matched contract and its audit trail: an evidence-graded protocol for turning fusion claims into comparable, condition-bounded measurements.

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Hou, H., Xia, T., Hu, L., Qin, H., Zhang, Y., Li, Y., Fang, S., Cao, L.. 2026-06-15. RepGene: Toward a Unified Gene Representation Space Robust to Missing Biological Views. https://doi.org/10.64898/2026.06.11.731512

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