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. Author manuscript; available in PMC: 2022 Mar 11.
Published in final edited form as: Sci Transl Med. 2021 May 19;13(594):eabc1739. doi: 10.1126/scitranslmed.abc1739

Figure 2. Prioritization of de novo missense variants using variant impact on pathways.

Figure 2.

(A) Hierarchical clustering of the 23 prioritized pathways is shown. For the 398 genes with missense variants that were associated with at least one relevant pathway, a matrix was created to denote whether the gene was (red) or was not (grey) a component of the pathway. Pathways were then grouped according to their patterns of affected genes via hierarchical clustering performed by GENE-E. (B) Evolutionary action score distribution for the synaptic transmission pathway is shown. Evolutionary action scores for the proband variants (red) and matched sibling variants (black) in this pathway were binned in deciles and represented as histograms. (C) Significance of all tested pathways in cohorts of patients with ASD and their matched siblings is presented. Each point represents one of the 368 tested pathways and is connected with a line to the same pathway in the matched cohort. The q = 0.1 significance threshold after False Discovery Rate (FDR) correction is represented as a dashed red line.