Fig. 2: Gene set enrichment analysis of deleterious gDNMs in BD.

a Gene ontology (GO) terms enriched among the genes hit by deleterious (LoF or damaging missense/inframe indel) gDNMs in BD at a false discovery rate (FDR) <0.1. FDR adjustment was performed based on the number of terms in the corresponding GO category (biological process, cellular component, or molecular function). Uncorrected P values for our observations (the red dotted lines) were calculated by DNENRCIH that considers confounding factors, such as gene sizes and local sequence contexts (“Methods”). The histograms indicate the distributions of the expected number of gDNMs hitting the corresponding GO term (the x axis), which was generated by one million random permutations by DNENRCIH. Top, BD; bottom, controls. b Network visualization of the GO terms enriched among the genes hit by deleterious gDNMs in BD at uncorrected P < 0.05. The node colors and label sizes indicate the statistical significance of enrichment (deep red indicates the most significant terms). The node sizes indicate the number of genes included in a term. The edge width is proportional to the overlap coefficient. The full list of GO terms with uncorrected P < 0.05 is shown in Supplementary Data 2. c Enrichment analysis of the genes hit by deleterious gDNMs in BD for the top 2% of the genes with the highest expression in each of the 54 human tissues in the GTEx dataset. Uncorrected P values calculated by DNENRICH are shown as bar plots. The dotted and solid lines indicate the nominal (P = 0.05) and the Bonferroni-corrected (P = 0.00093 = 0.05/54) significance threshold, respectively. Bars are color coded as shown on the lower right of the plot. d Enrichment analysis of the genes hit by deleterious gDNMs in BD for the top 2% of the genes with the highest expression in each developmental period of a brain region in the BrainSpan Human Developmental Transcriptome dataset. Cells are color coded by uncorrected P values calculated by DNENRICH as shown on the right of the grid cells.