data integration

Transcriptome–Methylome Integration often fails due to structural issues rather than biological absence. Key challenges include over-aggregation of CpG sites, variance mismatches, asymmetric data preprocessing, and inappropriate statistical models. Proper region mapping, variance assessment, covariate alignment, and cohort size evaluation are essential to detect true regulatory relationships. Addressing these factors before complex modeling improves interpretation and avoids false conclusions about methylation-expression associations.