Fig. 7: COSMIS score improves interpretation of de novo missense mutations from neurodevelopmental disorders.
From: The 3D mutational constraint on amino acid sites in the human proteome
a COSMIS score distributions for de novo missense mutations from neurodevelopmental disorder cases (Case) and from unaffected siblings of autism spectrum disorder probands (Control). Case variants (n = 2271) have a significantly more constrained spatial neighborhoods than control variants (n = 571) (median COSMIS −0.83 vs. −0.39, \(p=3.0\times {10}^{-13}\), two-sided Mann–Whitney U test). b Case variant enrichment analysis for intra- and inter-species constraint metrics at the 10th percentile of most constrained sites. COSMIS has the highest enrichment for cases (OR 3.6, 95% confidence interval [2.3, 5.7]). Error bars are 95% confidence intervals of ORs. Results of this OR analysis are consistent across thresholds other than the 10th percentile (Supplementary Fig. 9). The values for each cell of the contingency table used for the OR calculation in each percentile bin were reported in Supplementary Data 15. OR odds ratio. Source data are provided as a Source Data file.
