无需甲基化输入的全基因组 DNA 甲基化预测新范式

ICLR 2026 Poster accepted paper at ICLR 2026. DNA methylation (DNAm) is a key epigenetic modification that regulates gene expression and is pivotal in development and disease. However, profiling DNAm at genome scale is challenging: of $\textasciitilde$28 million CpG sites in the human genome, only about 1–3\% are typically assayed in common datasets due to technological limitations and cost. Recent deep learning approaches, including masking-based generative Transformer models, have shown promise in capturing DNAm–gene expression relationships, but they rely on partially observed DNAm values for unmeasured CpGs and cannot be applied to completely unmeasured samples. To overcome this barrier, we introduce MethylProphet, a gene-guided, context-aware Transformer model for whole-genome DNAm inference without any measured DNAm input.