How far can you borrow? Divergence limits of cross-species Gene Ontology enrichment in non-model organisms

Fecha de publicación: --
Fuente: PubMed "rice"
Brief Bioinform. 2026 Nov 2;27(6):bbag622. doi: 10.1093/bib/bbag622.ABSTRACTFunctional interpretation of omics data from non-model species almost always relies on borrowing Gene Ontology (GO) annotations from a model organism-often a distant one (Arabidopsis for plants, zebrafish or human for fish)-and running enrichment analysis on inferred orthologs. How far this practice can be pushed before the enrichment result degrades has never been quantified at the level practitioners use. We present the first systematic benchmark of the divergence-tolerance of cross-species GO-transfer enrichment, across six focal species spanning three eukaryotic kingdoms, each with 15-22 reference species tiling a continuous phylogenetic gradient. Set-level fidelity-measured as redundancy-robust Wang semantic similarity between transferred and experimental-truth enriched term sets-declines monotonically with distance, collapsing to chance at the clade boundary in some panels (fish, rice) while remaining well above it in others (insect, fungi, mammal) (half-collapse identity, ID50, ~40%-59%). At fixed distance, a richer reference raises recall but lowers precision, quantifying a long-recognized but unresolved trade-off. Conserved processes transfer reliably to distant references whereas taxon-specific processes do not, a pattern consistent across all six focal species tested. Whole-genome duplication degrades transfer only when ohnolog retention is high, showing up as sensitivity to the orthology method rather than a steeper decline. An independent, GO-free measure of expression conservation supports the curves in vertebrates. We condense these results into a focal-species × distance reliability guide and a step-by-step decision protocol that let researchers judge, before analysis, whether borrowed-GO enrichment can be trusted for their species and question.PMID:43002602 | DOI:10.1093/bib/bbag622