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DTSTAMP:20210916T132450Z
LOCATION:Jean-Jacques Rousseau
DTSTART;TZID=Europe/Stockholm:20210706T153000
DTEND;TZID=Europe/Stockholm:20210706T160000
UID:submissions.pasc-conference.org_PASC21_sess139_msa356@linklings.com
SUMMARY:Predicting Genotype-Specific Gene Regulatory Networks
DESCRIPTION:Minisymposium\n\nPredicting Genotype-Specific Gene Regulatory 
 Networks\n\nWeighill, Ben Guebila, Glass, Quackenbush, Platig\n\nThe major
 ity of disease-associated genetic variants are thought to have regulatory 
 effects, including disruption of transcription factor (TF) binding and alt
 eration of downstream gene expression. Identifying the way in which each p
 erson’s genotype affects their individual gene regulatory network wo
 uld provide important insight into disease etiology and enable improved ge
 notype-specific disease risk assessments and treatments. We developed EGRE
 T (Estimating the Genetic Regulatory Effect on TFs) which infers a genotyp
 e-specific gene regulatory network (GRN) for each individual in a study po
 pulation. EGRET begins by constructing a genotype-informed TF-gene prior n
 etwork derived using TF motif predictions, eQTL data, individual genotypes
 , and the predicted effects of genetic variants on TF binding. It then use
 s message passing to integrate this prior network with gene expression and
  TF protein-protein interaction data to produce a refined, genotype-specif
 ic regulatory network. We used EGRET to infer GRNs for two blood-derived c
 ell lines and identified genotype-associated, cell-line specific regulator
 y differences that we subsequently validated using allele-specific express
 ion, chromatin accessibility QTLs, and differential ChIP-seq TF binding. W
 e also inferred EGRET GRNs for three cell types from each of 119 individua
 ls and identified cell type-specific regulatory differences associated wit
 h diseases related to those cell types. Because genotypes are the only ind
 ividual-level data required, EGRET can be readily applied to disease cohor
 ts where only genetic information is available. <br />EGRET is available t
 hrough the Network Zoo R package (netZooR v0.9; netzoo.github.io).\n\nDoma
 in: CS and Math, Emerging Applications, Chemistry and Materials, Climate a
 nd Weather, Life Sciences
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