Fig. 3
Performance of disease gene prioritization compared to random permutation. a OMIM disease genes and provisional disease genes have significantly stronger prioritization Z-scores compared to permuted disease genes (T-test p-values: 2.16 × 10−532 and 5.38 × 10−80, respectively). We also observe that the predictions of the provisional OMIM genes are, on average, weaker than the other OMIM disease genes (T-test p-value: 1.89 × 10−7). Because we use a leave-one-out strategy when calculating prioritization Z-scores for genes that have already been associated to an HPO term, there is no prediction bias towards known associations. Therefore, this benchmark is informative of the power to predict novel associations (see methods). b We observe a significant relation (Spearman p-value: 1.01 × 10−4) between the burden of evidence that a gene is associated to a disease and the GADO prioritization Z-score. Most genes are scored by13 some additional refuted genes, denotated as squares or diamonds, are reported by ref. 8 and ref. 12 c We observe a clear relation between the prioritization Z-scores and the gene predictability scores (Pearson r = 0.54). We do not observe this relation in the permuted results. d Our gene prioritization Z-scores are significantly correlated (Pearson p-value: 1.67 × 10−23) to the number of likely pathogenic (LP) and pathogenic (P) variants reported for a gene in ClinVar
