Thursday, February 14, 2019

Abstract for keynote talk at MCBIOS '19, Birmingham, AL Mar 28-30th (* i0mcbios *)

Talk Title:

Brain Genomics


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 the 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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