Fig. 4. Histone acetylation differences in ASD.

a Top gene ontology enrichments when linking ASD hyperacetylated regions to proximal genes using GREAT²⁸. P-values were adjusted for multiple testing by FDR correction. b Top gene ontology enrichments when linking ASD hypoacetylated regions to proximal genes using GREAT²⁸. P-values were adjusted for multiple testing by FDR correction. c Schema to link H3K27ac regions with their cognate genes. H3K27ac peaks within promoters were directly assigned to the proximal gene. Distal H3K27ac peaks were assigned to genes using eQTL and Hi-C datasets. d Correlation between expression and acetylation changes for genes that have a differentially acetylated region within their promoter and are differentially expressed. P-value is from a linear model used to correlate differential expression with differential acetylation. The four separate quadrants are marked. e Cell type enrichments for the four quadrants in d. Enrichments were calculated using a logistic regression model and p-values, which are shown in parentheses, were adjusted for multiple testing using FDR correction. Only those enrichments with odds ratio >1 and FDR corrected p-value < 0.05 are shown. f Enrichment of cognate genes linked to differentially acetylated regions within mRNA co-expression modules. Modules with a significant relationship to diagnosis are marked along the y axes (red: increased expression in ASD; blue: decreased expression in ASD). Enrichments were calculated using a logistic regression model and p-values, which are shown in parentheses, were adjusted for multiple testing using FDR correction. Only those enrichments with odds ratio >1 and FDR corrected p-value < 0.05 are shown. g Relationship between expression and acetylation changes for differentially acetylated peaks linked to gene co-expression modules. The functional annotation for each module is represented in the top left corner. The association of each module to ASD diagnosis is represented in the top right corner as well as whether acetylation changes are contributory or compensatory to changes in expression.