Identification of endocrine-disrupting chemicals targeting key DCM-associated genes via bioinformatics and machine learning

小桶 基因 计算生物学 毒理基因组学 生物信息学 生物 全基因组关联研究 单核苷酸多态性 遗传学 转录组 基因表达 基因型
作者
Shu Li,Shuice Liu,Xuefei Sun,Liying Hao,Qinghua Gao
出处
期刊:Ecotoxicology and Environmental Safety [Elsevier]
卷期号:274: 116168-116168
标识
DOI:10.1016/j.ecoenv.2024.116168
摘要

Dilated cardiomyopathy (DCM) is a primary cause of heart failure (HF), with the incidence of HF increasing consistently in recent years. DCM pathogenesis involves a combination of inherited predisposition and environmental factors. Endocrine-disrupting chemicals (EDCs) are exogenous chemicals that interfere with endogenous hormone action and are capable of targeting various organs, including the heart. However, the impact of these disruptors on heart disease through their effects on genes remains underexplored. In this study, we aimed to explore key DCM-related genes using machine learning (ML) and the construction of a predictive model. Using the Gene Expression Omnibus (GEO) database, we screened differentially expressed genes (DEGs) and performed enrichment analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to DCM. Through ML techniques combining maximum relevance minimum redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) logistic regression, we identified key genes for predicting DCM (IL1RL1, SEZ6L, SFRP4, COL22A1, RNASE2, HB). Based on these key genes, 79 EDCs with the potential to affect DCM were identified, among which 4 (3,4-dichloroaniline, fenitrothion, pyrene, and isoproturon) have not been previously associated with DCM. These findings establish a novel relationship between the EDCs mediated by key genes and the development of DCM.
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