Author, as appears in the article.: Suriyalaksh, Manusnan; Raimondi, Celia; Mains, Abraham; Segonds-Pichon, Anne; Mukhtar, Shahzabe; Murdoch, Sharlene; Aldunate, Rebeca; Krueger, Felix; Guimera, Roger; Andrews, Simon; Sales-Pardo, Marta; Casanueva, Olivia
Department: Enginyeria Química
URV's Author/s: Guimera Manrique, Roger / Sales Pardo, Marta
Keywords: Life-span Genomics Genetics Bioinformatics metabolism longevity insulin/igf-1 identification expression evolution drosophila daf-16 bow-ties
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.
Thematic Areas: Multidisciplinary sciences Multidisciplinary
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: roger.guimera@urv.cat marta.sales@urv.cat
Author identifier: 0000-0002-3597-4310 0000-0002-8140-6525
Record's date: 2024-10-19
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.cell.com/iscience/fulltext/S2589-0042(21)01633-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2589004221016333%3Fshowall%3Dtrue
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Iscience. 25 (1): 103663-
APA: Suriyalaksh, Manusnan; Raimondi, Celia; Mains, Abraham; Segonds-Pichon, Anne; Mukhtar, Shahzabe; Murdoch, Sharlene; Aldunate, Rebeca; Krueger, Felix; (2022). Gene regulatory network inference in long-lived C. elegans reveals modular properties that are predictive of novel aging genes. Iscience, 25(1), 103663-. DOI: 10.1016/j.isci.2021.103663
Article's DOI: 10.1016/j.isci.2021.103663
Entity: Universitat Rovira i Virgili
Journal publication year: 2022
Publication Type: Journal Publications
Repositori URV