Comprehensive functional genomic resource and integrative model for the human brain
Program in Bioinformatics and Integrative Biology
Bioinformatics | Computational Biology | Computational Neuroscience | Genetic Phenomena | Genomics | Integrative Biology | Mental Disorders
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.
psychiatric disorders, PsychENCODE Consortium, genes, genome
DOI of Published Version
Science. 2018 Dec 14;362(6420). pii: eaat8464. doi: 10.1126/science.aat8464. Link to article on publisher's site
Science (New York, N.Y.)
Wang, Daifeng; Mattei, Eugenio; Moore, Jill E.; Weng, Zhiping; Geschwind, Daniel H.; Knowles, James A.; and Gerstein, Mark B., "Comprehensive functional genomic resource and integrative model for the human brain" (2018). Program in Bioinformatics and Integrative Biology Publications and Presentations. 146.