Gene regulatory network inference from CRISPR perturbations in primary CD4⁺ T cells elucidates the genomic basis of immune disease.

ABSTRACT: The effects of genetic variation on complex traits act mainly through changes in gene regulation. Although many genetic variants have been linked to target genes in cis, the trans-regulatory cascade mediating their effects remains largely uncharacterized. Mapping trans-regulators based on natural genetic variation has been challenging due to small effects, but experimental perturbations offer a complementary approach. Using CRISPR, we knocked out 84 genes in primary CD4⁺ T cells, targeting inborn error of immunity (IEI) disease transcription factors (TFs) and TFs without immune disease association. We developed a novel gene network inference method called linear latent causal Bayes (LLCB) to estimate the network from perturbation data and observed 211 regulatory connections betw

SUBMITTER: Weinstock JS 

PROVIDER: S-EPMC11605694 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature