Single Cell Sequencing and Integrative Analysis of Epigenetic and Transcriptomic Profiling in ASD

Despite ASD’s etiological heterogeneity, previous studies have shown patterns of molecular convergence in post-mortem brain tissue from autistic subjects. Here, I describe our new unpublished work using two approaches: 1) similarity network fusion (SNF) to integrate genome-wide measures of mRNA expression, miRNA expression, DNA methylation, and histone acetylation to identify a convergent molecular subtype of ASD and 2) single cell sequencing in control and ASD brain to identify cell type specific changes and pathways. Using the SNF approach, we identify a core subtype of ASD, and substantially expand the repertoire of differentially expressed genes in ASD and identify a component of upregulated immune processes that are associated with hypomethylation. We utilize eQTL and chromosome conformation datasets to link differentially acetylated regions with their cognate genes and find an enrichment of ASD genetic risk in hyperacetylated noncoding regulatory regions linked to neuronal genes. Similarly, single cell sequencing appears to substantially refine signals obtained from whole tissue. These findings help elucidate how diverse genetic risk factors converge onto specific molecular processes in ASD.