Beyond 850K: Accessing the Full Methylome with dWMS

As multi-omics trial designs become standard, dWMS provides the methylome layer required to complement transcriptomic and proteomic data without the technical debt or revalidation demands of legacy platforms.

The Post-Array Era of Epigenomic Discovery

For over a decade, Illumina’s high-density methylation arrays have defined the landscape of clinical epigenomics. The EPIC 850K Array, often considered the gold standard, enabled large methylation studies at scale, generating data that built today’s methylation knowledge base¹.

But that foundation came with a ceiling. Arrays capture fewer than 3% of the 28 million CpG sites in the human genome, largely biased toward promoter regions and previously characterized regulatory elements^2,3. This design inherently limits discovery, leaving extra-array areas like enhancer regions, long non-coding RNAs, and subtelomeric sites largely invisible to array-based profiling⁴.

To unlock the remaining 97% of the methylome, clinical epigenomics needs to move beyond probe panels toward native, base-resolution sequencing.

Renew's Direct Whole Methylome Sequencing (dWMS) service breaks through that limitation. Built on Oxford Nanopore’s long-read technology, dWMS sequences DNA in its native state, without bisulfite conversion, amplification, or information loss^5,6.

By reading methylation directly from native DNA strands, dWMS captures more than 97% of CpG sites genome-wide, encompassing enhancers, intragenic regions, long non-coding RNAs, and regulatory hotspots that arrays cannot access. The result is a single-assay workflow that delivers both genetic and epigenetic data with true single-base resolution.

Because dWMS is panel-free, the same data can be re-queried as new biology emerges, making it a future-proof foundation for discovery and translational research.

What the Data Show

Nanopore sequencing enables direct, chemical-free mapping of methylation and other base modifications that array chemistries often miss⁷. Whole-methylome studies have demonstrated base-resolution calls at ~26–28 million CpG sites, representing >92% of all CpGs, with the added ability to resolve allele- and haplotype-specific methylation^6,8.

Comparative studies show that even the highest-density arrays fail to capture more than half of the genome’s methylation signals, particularly in enhancer regions influencing transcriptional regulation⁹. Nanopore-derived methylation estimates not only align more closely with bisulfite benchmarks but also deliver broader coverage and finer resolution¹⁰.

These long-read approaches are already connecting methylation dynamics with gene expression in cancer and neurological disease, linking molecular mechanisms directly to phenotype^7,11.

Strategic Advantages Across the Clinical Pipeline

Discovery Without Boundaries
‍In exploratory trials and early-phase research, dWMS empowers discovery of methylation biomarkers far beyond canonical promoter regions. It enables comprehensive analysis of enhancer networks, chromatin modifiers, and intergenic regulatory loci that often drive disease heterogeneity and therapy resistance¹².

‍Validation and Companion Diagnostics
‍For biomarker validation, dWMS produces reproducible, quantitative methylation data suitable for integration with machine-learning classifiers and genomic risk models. Because the workflow is independent of predefined probes, evolving biomarker panels can be expanded without re-engineering the assay, accelerating companion diagnostic development and regulatory readiness¹³.

‍Precision Stratification
‍Comprehensive methylome data strengthen molecular stratification within heterogeneous patient cohorts. Even in the absence of canonical promoter methylation changes, dWMS can detect subtle subgroup signatures that inform enrollment and therapeutic targeting in trials.

Technical Edge: From Subtlety to Specificity

Arrays infer while dWMS resolves. These capabilities extend beyond research-use assays into the emerging domain of sequencing-based diagnostics and regulatory-grade analytics. That shift enables insights unreachable by any probe-based method.

Eliminated panel biases
Every genomic region, coding or non-coding, proximal or distal, is measurable.

‍Allele- and haplotype-specific detection
Reveals imprinting, mosaicism, and cis-regulatory variation influencing disease risk or drug response⁶.

Single-base precision
‍Captures subtle methylation shifts within enhancer-driven gene-regulatory networks.

The Market Shift Is Already Underway

Demand for sequencing-based methylation analysis is accelerating. Market projections indicate the methylation sequencing sector will exceed $1.3 billion by 2025, driven by ~17% compound annual growth in clinical and translational applications^14,15.

Regulators across North America, Europe, and Asia-Pacific are increasingly recognizing sequencing-based methylation biomarkers as viable components of in vitro diagnostic submissions¹⁶.

As multi-omics trial designs become standard, dWMS provides the methylome layer required to complement transcriptomic and proteomic data without the technical debt or revalidation demands of legacy platforms.

Renew Biotechnologies: Powering the Next Wave of Epigenomic Insight

Renew combines proprietary wet-lab optimization, Oxford Nanopore technology, and tailored bioinformatics pipelines to deliver end-to-end, direct whole methylome sequencing.

Our dWMS platform supports translational research, biomarker discovery, and clinical trial enablement., helping teams uncover the 97% of the methylome that arrays can’t see with scalable coverage to match your research and discovery. Whether you’re validating a biomarker, stratifying patients, or designing next-generation diagnostics, dWMS provides a scalable, future-ready foundation for precision epigenomics.