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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
Regional Methylation Analysis
Genome-wide CpG coverage for regional methylation discovery
Native 5mC, 5hmC, and 6mA methylation profiling
Sequence Variation Analysis
SNP and sequence variant analysis from the same dataset
Integrated genomic and methylation outputs in one workflow
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
Download panel showing four files for specimen 250409 with names, sizes, dates, and download options.
  • 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.
Renew combines platform flexibility, nanopore expertise, and operational excellence to resolve areas
of the genome that standard approaches cannot.
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