Gene regulatory network inference in long-lived C. elegans reveals modular properties that are predictive of novel aging genes.

ABSTRACT: We design a "wisdom-of-the-crowds" GRN inference pipeline and couple it to complex network analysis to understand the organizational principles governing gene regulation in long-lived glp-1/Notch Caenorhabditis elegans. The GRN has three layers (input, core, and output) and is topologically equivalent to bow-tie/hourglass structures prevalent among metabolic networks. To assess the functional importance of structural layers, we screened 80% of regulators and discovered 50 new aging genes, 86% with human orthologues. Genes essential for longevity-including ones involved in insulin-like signaling (ILS)-are at the core, indicating that GRN's structure is predictive of functionality. We used in vivo reporters and a novel functional network covering 5,497 genetic interactio

SUBMITTER: Suriyalaksh M 

PROVIDER: S-EPMC8753122 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature