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Comprehensive functional genomic resource and integrative model for the human brain.

Publication ,  Journal Article
Wang, D; Liu, S; Warrell, J; Won, H; Shi, X; Navarro, FCP; Clarke, D; Gu, M; Emani, P; Yang, YT; Xu, M; Gandal, MJ; Lou, S; Zhang, J ...
Published in: Science
December 14, 2018

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.

Duke Scholars

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Published In

Science

DOI

EISSN

1095-9203

Publication Date

December 14, 2018

Volume

362

Issue

6420

Location

United States

Related Subject Headings

  • Transcriptome
  • Single-Cell Analysis
  • Quantitative Trait Loci
  • Mental Disorders
  • Humans
  • Genome-Wide Association Study
  • General Science & Technology
  • Gene Regulatory Networks
  • Gene Expression Regulation
  • Epigenomics
 

Citation

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Wang, D., Liu, S., Warrell, J., Won, H., Shi, X., Navarro, F. C. P., … Gerstein, M. B. (2018). Comprehensive functional genomic resource and integrative model for the human brain. Science, 362(6420). https://doi.org/10.1126/science.aat8464
Wang, Daifeng, Shuang Liu, Jonathan Warrell, Hyejung Won, Xu Shi, Fabio C. P. Navarro, Declan Clarke, et al. “Comprehensive functional genomic resource and integrative model for the human brain.Science 362, no. 6420 (December 14, 2018). https://doi.org/10.1126/science.aat8464.
Wang D, Liu S, Warrell J, Won H, Shi X, Navarro FCP, et al. Comprehensive functional genomic resource and integrative model for the human brain. Science. 2018 Dec 14;362(6420).
Wang, Daifeng, et al. “Comprehensive functional genomic resource and integrative model for the human brain.Science, vol. 362, no. 6420, Dec. 2018. Pubmed, doi:10.1126/science.aat8464.
Wang D, Liu S, Warrell J, Won H, Shi X, Navarro FCP, Clarke D, Gu M, Emani P, Yang YT, Xu M, Gandal MJ, Lou S, Zhang J, Park JJ, Yan C, Rhie SK, Manakongtreecheep K, Zhou H, Nathan A, Peters M, Mattei E, Fitzgerald D, Brunetti T, Moore J, Jiang Y, Girdhar K, Hoffman GE, Kalayci S, Gümüş ZH, Crawford GE, PsychENCODE Consortium, Roussos P, Akbarian S, Jaffe AE, White KP, Weng Z, Sestan N, Geschwind DH, Knowles JA, Gerstein MB. Comprehensive functional genomic resource and integrative model for the human brain. Science. 2018 Dec 14;362(6420).
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

December 14, 2018

Volume

362

Issue

6420

Location

United States

Related Subject Headings

  • Transcriptome
  • Single-Cell Analysis
  • Quantitative Trait Loci
  • Mental Disorders
  • Humans
  • Genome-Wide Association Study
  • General Science & Technology
  • Gene Regulatory Networks
  • Gene Expression Regulation
  • Epigenomics