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Close-up of a multi-channel pipette dispensing green liquid into a multi-well plate in a lab.

Overview

Direct Methylation Sequencing (dMS) combines proprietary library preparation protocols with native Oxford Nanopore cfDNA sequencing to support cfDNA methylome profiling and liquid biopsy biomarker development without bisulfite conversion or PCR amplification.

Native cfDNA sequencing optimized for methylation analysis
Native 5mC, 5hmC, and 6mA profiling without bisulfite conversion
Integrated sequence and methylation analysis in a single workflow

Multiomic Liquid Biopsy

Integrated genomic and epigenetic analysis from one dataset
Expanded CpG coverage beyond traditional methylation arrays

Broad Sample Compatibility

Compatible with plasma, serum, CSF, and seminal fluid
Flexible support for research and biomarker development

Tissue-of-Origin Analysis

Native methylation profiling of circulating cfDNA fragments
Cell- and tissue-of-origin inference and characterization

Technology and Compatibility

dMS applies native ONT sequencing to cell-free DNA, enabling cfDNA methylome analysis and liquid biopsy biomarker discovery across diverse biofluids and research applications.

Download White Paper

Compatible with
Human and animal cfDNA samples
Plasma, serum, CSF, and seminal fluid biofluids
Research, translational, and biomarker development workflows

Component
Technology
Sequencing Chemistry
Native Oxford Nanopore cfDNA Sequencing
Preparation
Renew dMS library preparation
Sequencing Platform
Oxford Nanopore PromethION

1. cfDNA Extraction
High-quality cfDNA is isolated from samples.
2. Library Preparation
Proprietary dMS library preparation and adapter ligation.
3. cfDNA Sequencing
Native cfDNA is sequenced via 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.

Metric
Typical Performance (Human Samples)
Samples per Flow Cell
Up to 24
Average Coverage
0.1x-1.0x
Average Read Length
~500 bp N50
Available 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.

Download White Paper

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

Recommended Bioinformatics Packages
General ONT Analysis
Epi2Me
Epigenetic Analysis
ModSeqR, ModKit
SNV Calling
Clair3
STR Detection
LongTR, Straglr
Taxonomic Classification
Kraken
Long Read Genome Assembly
Flye, Hifiasm
Basecalling and Aligning
Dorado, MiniMap
Bam File Manipulation
Samtools
FASTQ Manipulation
SeqTK

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.

With each project, you’ll receive the following:
Experimental design consultation
Standardized QC protocols for data quality review
Live project updates through the customer portal
Access to open-source variant and methylation analysis pipelines
Flexible data delivery options
Post-project consultation and technical review
Access to data analysis and regulatory experts as needed

Questions & Answers

What is Direct Methylation Sequencing (dMS) for cell-free DNA?

Direct Methylation Sequencing (dMS) is a bisulfite-free, Oxford Nanopore–based whole-genome sequencing service for cell-free DNA (cfDNA). It uses unbiased nanopore sequencing with proprietary library preparation optimized for short cfDNA fragments to preserve native DNA methylation and other base modifications.

Can dMS for cfDNA be used for liquid biopsy research?

Yes. dMS can be used to analyze genome-wide methylation patterns in circulating DNA fragments from blood or other fluids. It is well suited for tissue-of-origin analysis and liquid biopsy research without the need for targeted panels or prior assumptions.

What makes Renew’s cfDNA methylation technology different from traditional methods?

dMS uniquely combines bisulfite-free, native Oxford Nanopore sequencing with proprietary cfDNA-optimized library preparation to preserve native epigenetic context. Unlike bisulfite- and PCR-based workflows, it analyzes methylation directly from fragmented cfDNA, enabling unbiased, genome-wide detection of methylation and other base modifications for discovery-driven liquid biopsy research.

How does Renew’s dMS for cfDNA improve sensitivity?

By avoiding chemical conversion and amplification, dMS minimizes DNA damage and representation bias. This preserves more cfDNA molecules and their methylation signals, enabling sensitive, single-molecule methylation analysis even from low-input or low-abundance samples.

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

Direct Methylation Sequencing (cfDNA)