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• W4200201619 endingPage "103663" @default.
• W4200201619 startingPage "103663" @default.
• W4200201619 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 interactions to make mechanistic predictions. We used genetic epistasis to test some of these predictions, uncovering a novel transcriptional regulator, sup-37, that works alongside DAF-16/FOXO. We present a framework with predictive power that can accelerate discovery in C. elegans and potentially humans." @default.
• W4200201619 created "2021-12-31" @default.
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• W4200201619 date "2022-01-01" @default.
• W4200201619 modified "2023-09-29" @default.
• W4200201619 title "Gene regulatory network inference in long-lived C. elegans reveals modular properties that are predictive of novel aging genes" @default.
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• W4200201619 doi "https://doi.org/10.1016/j.isci.2021.103663" @default.
• W4200201619 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35036864" @default.
• W4200201619 hasPublicationYear "2022" @default.
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