Work

Effects of chlorpyrifos exposure on autism-associated genes: an integrative analysis using network toxicology, transcriptomics, and molecular dynamics simulations

Year: 2026

Type: article

Abstract: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by deficits in social communication and restricted, repetitive behaviors or interests. The development of ASD involves complex interactions between genetic and environmental factors. This study aims to investigate potential molecular links between target genes of chlorpyrifos and ASD, thereby elucidating potential mechanisms by which environmental exposures contribute to ASD development and exploring candidate biomarkers. We analyzed the ASD dataset GSE18123, autism-related genes (ARGs), and chlorpyrifos target-related genes (CRGs). A total of 206 autism and chlorpyrifos target-related genes (ACRGs) were identified. Through protein-protein interaction (PPI) network analysis, six hub genes ( MYC , HIF1A , SP1 , CXCL8 , IFNG , and IL10 ) were screened. Functional enrichment analyses indicated that these ACRGs are primarily involved in energy metabolism and immune/inflammatory regulation. Using least absolute shrinkage and selection operator (LASSO) penalized logistic regression, an exploratory four-gene signature ( CXCL8 , IFNG , MYC , and SP1 ) was identified, which showed discriminatory ability in the current dataset. Moreover, immune cell infiltration analysis via single-sample gene set enrichment analysis (ssGSEA) indicated significant differences in 10 immune cell types, which were correlated with key genes. Molecular docking and dynamics simulations suggested potential binding interactions of MYC with methylprednisolone and SP1 with terameprocol, providing preliminary computational clues for further experimental validation. Our findings revealed an exploratory four-gene signature linked to chlorpyrifos exposure and ASD, and suggested that MYC and SP1 may represent candidate molecules for future validation in therapeutic studies. These results provide new insights into the interaction between environmental exposures and genetic factors in ASD, offering novel clues for future research in precision diagnosis and potential therapeutic exploration.

Source: Brain Informatics

DOI: 10.1186/s40708-026-00329-7

Authors: Boli Cheng, Enyu Wan, Xiaoqin Wei, Si Wang, Yun He, Xiaojiang Lyu

Institutions: North Sichuan Medical University, Affiliated Hospital of North Sichuan Medical College

Language: English

Topic: Autism Spectrum Disorder Research

Subfield: Cognitive Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,090