Extended Data Fig. 4: Additional validation analyses.
From: Bayesian estimation of gene constraint from an evolutionary model with gene features
a, Precision–recall curves comparing the performance of shet estimates from GeneBayes against LOEUF from gnomAD v4.0.0 (731k exomes) or LOEUF from gnomAD v2.1.1 (125k exomes) in classifying essential genes. b, Precision–recall curves comparing the performance of shet estimates from GeneBayes against other constraint metrics in classifying nonessential genes. c, Precision–recall curves comparing the performance of shet against other constraint metrics in classifying developmental disorder genes. d, Enrichment of de novo mutations in patients with developmental disorders, calculated as the observed number of mutations over the expected number under a null mutational model (n = 31,058 parent–offspring trios). We plot the enrichment of synonymous, missense, splice and nonsense variants in the 10% of genes considered most constrained by shet (blue) and the enrichment of these variants in all other genes (gray), including (left) and excluding (right) known developmental disorder genes. Bars represent 95% confidence intervals, centered around the mean. e, Scatterplot of the enrichment of common variant heritability in the 10% of genes considered most constrained by shet (y axis) or LOEUF (x axis), normalized by the enrichment of heritability in all genes. Each point represents one trait.
