Daifeng Wang, PhD – Slide of the Week

Title: Cell-type associated gene regulatory networks in the human brain

Legend: The circos plots show the linkages from gene regulatory network targeting various cell-type–specific biomarker genes in the human brain. Selected TFs for particular cell types are highlighted.

Citation: Wang D, Liu S, Warrell J, Won H, Shi X, Navarro FCP, Gerstein MB, et al. (2018). Comprehensive functional genomic resource and integrative model for the human brain. Science, 362(6420). pii: eaat8464. doi: 10.1126/science.aat8464.

Abstract: Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The PsychENCODE resource contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles for many cell types; expression quantitative-trait loci (QTLs); and further QTLs associated with chromatin, splicing, and cell-type proportions. Integration shows that varying cell-type proportions largely account for the cross-population variation in expression (with >88% reconstruction accuracy). It also allows building of a gene regulatory network, linking genome-wide association study variants to genes (e.g., 321 for schizophrenia). We embed this network into an interpretable deep-learning model, which improves disease prediction by ~6-fold versus polygenic risk scores and identifies key genes and pathways in psychiatric disorders.

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