Blood-based DNA methylation markers for autism spectrum disorder identification using machine learning

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder lacking objective biomarkers for early diagnosis. DNA methylation is a promising epigenetic marker, and machine learning offers a data-driven classification approach. However, few studies have examined whole-blood, genome-wide DNA methylation profiles for ASD diagnosis in school-aged children. We analyzed genome-wide DNA methylation data from GEO dataset GSE113967, including 52 children with ASD and 48 typically developing (TD) controls. Differentially methylated positions (DMPs) were identified, and feature selection was performed using support vector machine-recursive feature elimination with cross-validation (SVM-RFECV). Classification models were developed using random forest (RF), extreme gradient boosting (XGBoost), and decision tree (DT) classifiers. A nomogram visualized feature contributions. A total of 138 DMPs differentiated ASD from TD children. Eleven CpG sites selected by SVM-RFECV formed the basis for model construction. RF and XGBoost achieved the highest accuracy (75%), with DT reaching 70%. Functional annotation indicated enrichment in cell adhesion and immune-related pathways. This exploratory study demonstrates the feasibility of integrating peripheral blood DNA methylation data with machine learning to distinguish children with ASD. While limited by sample size and moderate accuracy, this study provides methodological insights into the feasibility of integrating epigenetic and computational approaches for ASD-related biomarker exploration. Autism spectrum disorder (ASD) is a condition that affects how children communicate, interact with others, and behave. Right now, doctors diagnose ASD by watching a child’s behavior, which can take time and delay early help. In this study, we looked at small chemical changes in the blood that may affect how genes work. These changes can sometimes show if a child has ASD. We used computer programs to find patterns in these changes that could help tell children with ASD apart from those without it. While the study included a small number of children and more research is needed, our results suggest that a simple blood test could one day help doctors detect ASD earlier and more accurately.