Direct Whole Methylome Sequencing

dWMS: A Paradigm Shift in Methylation Research

Wasatch BioLabs' Direct Whole Methylome Sequencing (dWMS) overcomes key limitations in traditional methylation methods, offering:

  • High-Throughput Multiplexing: Enables cost-effective, low-pass sequencing ideal for large-scale methylation studies and biomarker discovery.
  • Native DNA Sequencing: Avoids conversion and amplification errors, enhancing data quality by preserving native methylation patterns.
  • Ease of Use: Integrates seamlessly with MethylSeqR for streamlined transition from arrays, with compatible formats and analysis pipelines.
  • Comprehensive Genome Coverage: Offers complete methylome access (>27 M CpG sites) beyond predefined regions.

Output - Comparison

In addition to DNA sequence, WBL’s dWMS technology simultaneously captures the following features*: 

  • Short Tandem Repeat Expansions (STRs, dependent on read length & depth)
  • Copy Number Variants (CNVs, dependent on read length & depth)
  • Phasing Data (dependent on read length and depth)
  • Modified Bases (5mC, 5hmC; and bacterial 6mA)
  • Single Nucleotide Polymorphisms (SNPs)
  • Large Structural Variants

*Subject to variation depending on sample quality and the complexity of target regions.

Direct-
Application

Wasatch BioLabs' dWMS broadens horizons in biomarker discovery, multi-omics research, and clinical applications. Providing richer insights across the genome without the limitations of traditional methylation profiling technologies, dWMS facilitates:

Expanded Biomarker Discovery ¬

Capturing up to 99% of CpG methylation sites across the human genome, dWMS enables the detection of methylation signatures with potential regulatory roles in gene expression and disease mechanisms. Applications include:

Autoimmune Disorders
Neurological Conditions
Other Disease Areas
Oncology

Accessible Multi-Omics Research ¬

Designed for projects requiring both genomic and epigenomic data, dWMS integrates seamlessly into multi-omics pipelines. Researchers can capture and analyze native genome-wide methylation patterns and sequence variations in single runs, offering a comprehensive view for studies focused on:

Systems Biology
Environmental Epigenetics
Disease Mechanisms
Other Applications Requiring Integrated Genomic Insights

Clinical Utility ¬

For researchers focused on translating genomic and epigenomic discoveries into clinical applications, Wasatch BioLabs offers tailored assay development pathways.

Begin with dWMS for genome-wide biomarker discovery and validation, then transition smoothly into clinical assay development using WBL’s bisulfite-free protocols. This streamlined pipeline provides an efficient path from discovery to clinical application, maximizing research value at each stage.

CpG Coverage:
dWMS vs Methylation Microarray

dWMS offers broader methylome coverage, capturing 2.4 times more differentially methylated CpG islands (CGIs) between blood and sperm than traditional arrays.

dWMS identifies significantly more differentially methylated CpG islands (CGIs) than traditional microarrays. DNA was extracted from blood (n=4) and sperm (n=4) and analyzed using both methylation arrays and dWMS. The dWMS method captured 2.4 times more CGIs with significant differential methylation, including 91% of those detected by the array.

Minimal Batch Effectsaa

dWMS displays minimal batch effects—high intra-group similarity and low inter-group similarity between blood and sperm-derived DNA, underscoring dWMS’s reliability for scalable epigenetic research and clinical assay development.

Minimal Batch Effectsb

WBL’s dWMS demonstrates high reproducibility with minimal inter-sample variance within each group. DNA from blood (n = 4) and sperm (n = 4) samples was sequenced on two different machines. The correlation matrix (A) and principal component analysis (PCA) plot display high similarity within the blood and sperm groups, underscoring the platform's consistency.

Clinical Utility: Cell-Of-Origin Analysis

dWMS enables the precise identification of cell-type-specific methylation signatures with single-molecule resolution. This approach allows for the bioinformatic determination of cell-of-origin, leveraging complex, multi-CpG methylation patterns.

dWMS identifies cell-type-specific methylation signatures, tracing DNA back to its cell of origin. DNA was extracted from blood (n=1) and purified neurons (cortical, n=1; spinal motor, n=1), then sequenced with dWMS. A representative 101 bp differentially methylated region highlights methylation patterns unique to cortical neurons, with each ONT track showing single reads: red marks methylated sites, blue unmethylated.

MethylSeqR Package Highlights ¬

  • High-Speed Performance: The entire pipeline from raw data to differential methylation p-values across 27 million+ CpGs completes in about 80 seconds on a laptop (4 cores, 8 GB RAM). Sliding window calculations (approx. 3 billion) finish in 15 minutes.
  • Simple and Powerful Workflow: Wrapper scripts enable a complete analysis with just three function calls: import data, run QC, and execute analysis.
  • Efficient Storage: Reduces 20 GB modkit outputs to 1 GB, streamlining data transfer and storage.
  • Optimized Memory: Utilizes an on-disk database to handle tasks larger than system memory.

(A) Positional Summary

(B) Summaries By Region

MethylSeqR converts ONT methylation data to array-like formats.
Representative examples of MethylSeqR outputs by positional (A) and regional (B) summaries.

Within seconds, researchers can access familiar data views:

Methylation summs by base position
Sliding window analysis
Quality control functions
CpG Islands
Differential expression by region, read, position

Making Direct Methylation Accessible

Wasatch BioLabs introduces MethylSeqR, a user-friendly R package that simplifies the transition from methylation arrays to dWMS. This powerful bioinformatics tool integrates seamlessly into existing array-based workflows, enabling researchers to unlock the full potential of native whole-genome methylation data with streamlined analysis and enhanced insights.

WBL: Your Competitive Edge

Maximize your sequencing output with WBL’s leading technology, streamlined bioinformatics pipelines, and expert guidance. WBL’s team of researchers are pioneers in Oxford Nanopore Technologies sequencing with decades of experience in genomics and bioinformatics research.

Speak To a Specialist
Speak To A Specialist

Robust Data

NGS 3.0 data with fully streamlined bioinformatics pipelines.

Fast Turnarounds

Results within 14-21 days of your sample’s arrival at the lab.

Expert Guidance

Teams of dedicated researchers and project managers to support your research and development.

Full Visibility

Direct access to an online portal for sample information and batch status at each step of the sequencing process.

Specialized Offerings In Our
Next-Generation BioLab

Explore our other NGS services

whole genome sequencing
whole genome sequencing
Biomarker Discovery
Biomarker Discovery
Clinical Services
Clinical Services
Bisulfite-Free Targeted Methylation Sequencing
Bisulfite-Free Targeted Methylation Sequencing
cfDNA Whole Genome Methylation Sequencing
cfDNA Whole Genome Methylation Sequencing

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