Mapping the functional impact of non-coding regulatory elements in primary T cells through single-cell CRISPR screens.

ABSTRACT:

Background

Drug targets with genetic evidence are expected to increase clinical success by at least twofold. Yet, translating disease-associated genetic variants into functional knowledge remains a fundamental challenge of drug discovery. A key issue is that the vast majority of complex disease associations cannot be cleanly mapped to a gene. Immune disease-associated variants are enriched within regulatory elements found in T-cell-specific open chromatin regions.

Results

To identify genes and molecular programs modulated by these regulatory elements, we develop a CRISPRi-based single-cell functional screening approach in primary human T cells. Our pipeline enables the interrogation of transcriptomic changes induced by the perturbation of regulatory elements at scale. We fir

SUBMITTER: Alda-Catalinas C 

PROVIDER: S-EPMC10835965 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature