Deep learning predicts DNA methylation regulatory variants in specific brain cell types and enhances fine mapping for brain disorders.

ABSTRACT: DNA methylation (DNAm) is essential for brain development and function and potentially mediates the effects of genetic risk variants underlying brain disorders. We present INTERACT, a transformer-based deep learning model to predict regulatory variants affecting DNAm levels in specific brain cell types, leveraging existing single-nucleus DNAm data from the human brain. We show that INTERACT accurately predicts cell type-specific DNAm profiles, achieving an average area under the receiver operating characteristic curve of 0.99 across cell types. Furthermore, INTERACT predicts cell type-specific DNAm regulatory variants, which reflect cellular context and enrich the heritability of brain-related traits in relevant cell types. We demonstrate that incorporating predicted variant effects and DN

SUBMITTER: Zhou J 

PROVIDER: S-EPMC11691643 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature