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Overview

Direct Whole Methylome Sequencing (dWMS) combines proprietary library preparation protocols with native Oxford Nanopore 5X whole-genome sequencing to support scalable genome-wide methylation profiling without bisulfite conversion or PCR amplification.
  • Low-pass whole-genome sequencing optimized for native methylation analysis
  • Native 5mC, 5hmC, and 6mA profiling without bisulfite conversion
  • Integrated sequence and methylation analysis in a single workflow
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Regional Methylation Analysis
Genome-wide CpG coverage for regional methylation discovery
Native 5mC, 5hmC, and 6mA methylation profiling
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Sequence Variation Analysis
SNP and sequence variant analysis from the same dataset
Integrated genomic and methylation outputs in one workflow
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Array-Compatible Workflows
ModSeqR conversion for array-like methylation analysis
Compatibility with minfi, DMRcate, and chAMP workflows
Technology
Workflow
Performance
Data Outputs

Technology and Compatibility

dWMS applies shallow native ONT long-read sequencing to genomic DNA from diverse organisms and sample types, enabling scalable genome-wide methylation analysis across a wide range of species.
  • Compatible with
  • DNA from human, animal, plant, microbial, and non-model organisms
  • Fresh, frozen, cultured, and extracted DNA sample types
  • Research, translational, and methylome characterization workflows
  • Component
    Technology
  • Sequencing Chemistry
    Native Oxford Nanopore DNA Sequencing
  • Preparation
    Renew dWMS library preparation
  • Sequencing Platform
    Oxford Nanopore PromethION

Workflow

Direct Whole Methylome Sequencing uses Renew’s optimized native long-read DNA sequencing workflow for low-pass methylome analysis. Renew provides full-service support from gDNA extraction through library preparation, sequencing, analysis, and data delivery.
  • 1. gDNA Extraction
    High-quality genomic DNA is isolated from samples
  • 2. Library Preparation
    Proprietary dWMS library preparation and adapter ligation
  • 3. Long-Read Sequencing
    Native RNA sequencing is performed on the PromethION platform.
  • 4. Data Analysis
    Sequencing data are processed through automated analysis pipelines.
  • 5. Data Delivery
    Results are delivered through the customer portal or AWS S3.

Sequencing Performance

Coverage and yield vary by genome size, input quality, multiplexing strategy, and study goals. Representative performance metrics for low-pass human dWMS are shown below.
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  • Metric
    Typical Performance (Human Samples)
  • Samples per Flow Cell
    Dependent on genome size
  • Average Coverage
    ~5X
  • Average Read Length
    ~1 kb N50
  • CpG Coverage
    > 95% CpG Coverage
  • Available Epigenetic Signals
    5mC, 5hmC, 6mA, non-CpG methylation

Bioinformatics and Data Outputs

Data outputs are designed to optimize data storage, transfer, and analysis. Methylation data is provided in a unique CH3 file format which reduces data size by up to 95%. This memory-efficient format stores data in an on-disk database, enabling larger-than-memory tasks.
Renew developed the ModSeqR R package, which converts ONT methylation data into array-like formats compatible with tools such as minfi, DMRcate, and chAMP. This solution empowers researchers to efficiently leverage dWMS data within familiar frameworks, facilitating advanced epigenetic insights.
Get ModSeqR on GitHub
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  • Data Outputs
  • QC Report
    Sequencing metrics and run statistics
  • BAM
    Aligned reads
  • CH3
    Base modifications
  • POD5
    Raw sequencing data (available for an additional fee)
  • Data Delivery Options
  • Client Web Portal
    Manual download | Mac, Linux, Windows
  • AWS S3 Transfer
    Automated process | AWS to AWS
  • Command Line Script
    Manual download | Mac, Linux

Service Inclusions

Each project is supported by dedicated project management and cross-functional expertise across assay development, bioinformatics, and regulatory strategy. Renew provides proactive communication, transparent project tracking, and technical support from study design through data delivery.

Questions & Answers

What is Direct Whole Methylome Sequencing (dWMS) for gDNA, and how can it help my research?

dWMS is Renew’s long-read, Oxford Nanopore–based whole-genome sequencing service for integrated genomic and epigenomic profiling. By sequencing native DNA directly, dWMS captures genome-wide methylation without bisulfite conversion while preserving full genomic context. In the human genome, this corresponds to coverage of more than 27 million CpG sites. With scalable coverage, dWMS supports unbiased discovery, biomarker development, translational research, and clinical assay development.

How is this sequencing method different from traditional methylation sequencing techniques?

dWMS uses long-read Oxford Nanopore sequencing to directly measure methylation from native DNA, eliminating bisulfite conversion and associated bias. It enables base-resolution detection of multiple DNA modifications and captures ~30× more CpG sites and ~2× more CpG islands than arrays for comprehensive, genome-wide methylation profiling.

How does Renew process and analyze nanopore sequencing data?

Renew converts raw nanopore data into CH3 files, an analysis-ready format that preserves native-read information. These files can be analyzed by Renew or by clients using ModSeqR, our R package for accessible summary, visualization, and interpretation of whole genome methylation data. For projects with more specialized requirements, Renew also offers custom bioinformatics pipeline development tailored to specific research and clinical objectives.

What are the sample requirements and how do I submit my samples?

Sample requirements vary by sample type and project goals. dWMS has been validated across 15+ sample types, including human tissue, whole blood, saliva, and plant and animal samples. Coverage can be tailored (from ~5× to 50×+) depending on whether your project's goals.

To submit samples or confirm requirements, contact Renew to connect with our technical team.

How do I begin a dWMS project with Renew?

Getting started is easy. Contact the Renew team to discuss your project goals in a one-on-one consultation. Our experts in genomics, epigenomics, and long-read sequencing will help design a tailored workflow and guide your project from study design through data delivery.

What are the benefits of a whole-genome dWMS approach?

A whole-genome dWMS approach provides an unbiased, comprehensive view of DNA methylation across the entire genome, including regulatory, repetitive, and noncoding regions that targeted methods and arrays often miss. By capturing methylation alongside sequence variation and structural context in a single assay, dWMS supports biological insight, biomarker discovery, and scalable translational and clinical study designs.

Renew combines platform flexibility, nanopore expertise, and operational excellence to resolve areas
of the genome that standard approaches cannot.
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