Advantages of Oxford Nanopore Technologies direct DNA/RNA sequencing for epigenetic profiling over traditional technologies

Epigenetic regulation—orchestrated by DNA methylation, histone modifications, non-coding RNAs, and emerging RNA base modifications—dictates gene expression, cell identity, and environmental responses. Yet, conventional methods like bisulfite sequencing and ChIP-seq impose critical limitations: they require harsh chemical treatments (e.g., bisulfite conversion) or artificial cross-linking that distort in vivo epigenetic states, obscure dynamic modifications, and sacrifice strand specificity. Here, Oxford Nanopore Technologies (ONT) direct sequencing is advocated as a transformative solution. By enabling native, amplification-free interrogation of DNA and RNA with ultra-long reads and real-time analysis, ONT uniquely captures the epigenome in near-physiological condition. It directly detects diverse base modifications—including 5 mC, 5 hmC, m6A, and pseudouridine, etc.—without engineered antibodies or destructive chemistry, while preserving critical strand orientation and phasing adjacent marks. Crucially, the present comparative analysis confirms ONT’s superior accuracy for modified base calling, enhanced sensitivity to low-abundance epigenetic variants, and unparalleled scalability for multi-omic integration. This fidelity to native molecular states positions ONT to redefine epigenetic research across basic, translational, and applied biology, establishing a new paradigm for resolving dynamic epigenetic landscapes in health and disease, as well as crop adaptation to internal/external cues.