Understanding Transcriptional Regulatory Redundancy by Learnable Global Subset Perturbations.

ABSTRACT: Transcriptional regulation through cis-regulatory elements (CREs) is crucial for numerous biological functions, with its disruption potentially leading to various diseases. It is well-known that these CREs often exhibit redundancy, allowing them to compensate for each other in response to external disturbances, highlighting the need for methods to identify CRE sets that collaboratively regulate gene expression effectively. To address this, we introduce GRIDS, an in silico computational method that approaches the task as a global feature explanation challenge to dissect combinatorial CRE effects in two phases. First, GRIDS constructs a differentiable surrogate function to mirror the complex gene regulatory process, facilitating cross-translations in single-cell modalities. It then employs l

SUBMITTER: Liu J 

PROVIDER: S-EPMC12694376 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature