Machine Learning-Based Prediction of Autism Spectrum Disorder and Discovery of Related Metagenomic Biomarkers with Explainable AI

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social communication deficits and repetitive behaviors. Recent studies have suggested that gut microbiota may play a role in the pathophysiology of ASD. This study aims to develop a classification model for ASD diagnosis and to identify ASD-associated biomarkers by analyzing metagenomic data at the taxonomic level. Methods: The performances of five different methods were tested in this study. These methods are (i) SVM-RCE, (ii) RCE-IFE, (iii) microBiomeGSM, (iv) different feature selection methods, and (v) a union method. The last method is based on creating a union feature set consisting of the features with importance scores greater than 0.5, identified using the best-performing feature selection methods. Results: In our 10-fold Monte Carlo cross-validation experiments on ASD-associated metagenomic data, the most effective performance metric (an AUC of 0.99) was obtained using the union feature set (17 features) and the AdaBoost classifier. In other words, we achieve superior machine learning performance with a few features. Additionally, the SHAP method, which is an explainable artificial intelligence method, is applied to the union feature set, and Prevotella sp. 109 is identified as the most important microorganism for ASD development. Conclusions: These findings suggest that the proposed method may be a promising approach for uncovering microbial patterns associated with ASD and may inform future research in this area. This study should be regarded as exploratory, based on preliminary findings and hypothesis generation.