Additional file 5: Figure S5. of A visual and curatorial approach to clinical variant prioritization and disease gene discovery in genome-wide diagnostics

Causal variant gene prioritization in solved clinical cohort cases and semantic algorithm score comparison. OE transitively computed a median rank of 3 (top 1 %) for host genes via maximum annotated Resnik similarity score, and 2 (top 1 %) via maximum ancestral overlap. As comparator metrics to the transitive prioritization approaches, we computed scores using direct HPO term-to-gene annotations and unions of phenotypes collapsed from the all diseases associated with each gene via the OMIM Morbidmap. The cumulative distribution curve demonstrates the quality of solutions within a given rank as the percentage of the 47 cases with variant genes correctly ranked at a given threshold. We report the median because it robustly separates the top half of a sample from the bottom half. The transitive maximum ancestral overlap method achieved the lowest median rank, while the transitive maximum OMIM catalog-weighted ancestral overlap method achieved the highest median rank percentile. (PDF 9 kb)