A network-based method for associating genes with autism spectrum disorder

Front Bioinform. 2024 Mar 8:4:1295600. doi: 10.3389/fbinf.2024.1295600. eCollection 2024.

Abstract

Autism spectrum disorder (ASD) is a highly heritable complex disease that affects 1% of the population, yet its underlying molecular mechanisms are largely unknown. Here we study the problem of predicting causal genes for ASD by combining genome-scale data with a network propagation approach. We construct a predictor that integrates multiple omic data sets that assess genomic, transcriptomic, proteomic, and phosphoproteomic associations with ASD. In cross validation our predictor yields mean area under the ROC curve of 0.87 and area under the precision-recall curve of 0.89. We further show that it outperforms previous gene-level predictors of autism association. Finally, we show that we can use the model to predict genes associated with Schizophrenia which is known to share genetic components with ASD.

Keywords: ASD genes; autism spectrum disorder (ASD); machine learning; network propagation; random forest.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by a research grant from the Israel Science Foundation (IPMP grant no. 2417/20).