Tissue-specific RNA methylation prediction from gene expression data using sparse regression models

N6-methyladenosine (m⁶A) is a highly prevalent and conserved post-transcriptional modification observed in mRNA and long non-coding RNA (lncRNA). Identifying potential m⁶A sites within RNA sequences is crucial for unraveling the potential influence of the epitranscriptome on biological processes. In this study, we introduce Exp2RM, a novel approach that formulates single-site-based tissue-specific elastic net models for predicting tissue-specific methylation levels utilizing gene expression data. The resulting ensemble model demonstrates robust predictive performance for tissue-specific methylation levels, with an average R-squared value of 0.496 and a median R-squared value of 0.482 across all 22 human tissues. Since methylation distribution varies among tissues, we trained the model to incorporate similar patterns, significantly improves accuracy with the median R-squared value increasing to 0.728. Additonally, functional analysis reveals Exp2RM's ability to capture coefficient genes in relevant biological processes. This study emphasizes the importance of tissue-specific methylation distribution in enhancing prediction accuracy and provides insights into the functional implications of methylation sites.