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Preserved in Portico This version is not peer-reviewed
Underexplored Molecular Mechanisms of Toxicity
Version 1
: Received: 31 May 2024 / Approved: 31 May 2024 / Online: 3 June 2024 (08:37:12 CEST)
A peer-reviewed article of this Preprint also exists.
Arowolo, O.; Suvorov, A. Underexplored Molecular Mechanisms of Toxicity. J. Xenobiot. 2024, 14, 939-949. Arowolo, O.; Suvorov, A. Underexplored Molecular Mechanisms of Toxicity. J. Xenobiot. 2024, 14, 939-949.
Abstract
Social biases may concentrate attention of researchers on a small number of well-known molecules/mechanisms leaving others underexplored. In accordance with this view, central to mechanistic toxicology is a narrow range of molecular pathways that are assumed to be involved in significant part of responses to toxicity. It is unclear, however, if there are other molecular mechanisms which play important role in toxicity events but are overlooked by toxicology. To identify overlooked genes sensitive to chemical exposures we used publicly available databases. First, we used data on published chemical-gene interactions for 17,338 genes to estimate their sensitivity to chemical exposures. Next, we extracted data on publication numbers per gene for 19,243 human genes from Find My Understudied Genes database. Threshold were applied to both datasets using our algorithm to identify chemically sensitive and chemically insensitive genes and well-studied and underexplored genes. 1,110 underexplored genes highly sensitive to chemical exposures were used in GSEA and Shiny GO analyses to identify enriched biological categories. Metabolism of fatty acids, amino acids, and glucose were identified as underexplored molecular mechanisms sensitive to chemical exposures. These findings suggest that future effort is needed to uncover the role of xenobiotics in the current epidemics of metabolic diseases.
Keywords
publication bias; underexplored pathways; toxicity mechanisms
Subject
Biology and Life Sciences, Toxicology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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