Predicting the effect of non-coding mutations on single-cell DNA methylation using deep learning
Liu, Z.; Gu, A.; Bao, Y.; Lin, G. N.
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Predicting the effects of non-coding mutations on DNA methylation is crucial for advancing our understanding of gene expression, epigenetic inheritance, and its role in disease mechanisms. Current methods lack the capability to predict the impact of non-coding mutations on DNA methylation at single-cell resolution and long range, while remain challenges in tracking SNP influences throughout disease progression. Here, we introduce Methven, a deep learning-based framework designed to predict the effects of non-coding mutations on DNA methylation at single-cell resolution, to overcome the challenges. Methven integrates DNA sequences and ATAC-seq data, employing a divide-and-conquer approach to handle varying scales of SNP-CpG interactions. By leveraging a pretrained DNA language model, Methven accurately predicts both the direction and magnitude of methylation changes across a 100kbp range with a lightweight architecture. The evaluation results demonstrate the superior performance of Methven in prioritizing functional non-coding mutation, model interpretability, and its potential for revealing personalized mutation-disease associations.
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