Direct Whole Methylome Sequencing (CFDNA)

A Paradigm Shift in Liquid Biopsy

Liquid biopsies are transforming precision medicine by providing non-invasive insights into health and disease. Wasatch BioLabs’ Direct Methylation Sequencing (dMS) for cfDNA addresses traditional methods limitations with optimized protocols and native nanopore sequencing, delivering precision, data with unmatched resolution and reliability.

• Comprehensive Insights

Capture the cfDNA methylome with single-molecule resolution, analyzing millions of CpG sites beyond the limits of traditional arrays.

• Ensure Reliable Results

Coherent data & optimized workflows preventing bisulfite damage & location-based batch effects fragmented cfDNA.

Protocols Optimized For Damaged DNA

Accurately analyzing methylation from fragmented, low-concentration cfDNA is one of the greatest challenges of liquid biopsies. Traditional workflows introduce biases, damage DNA, and compromise the integrity of critical methylation signals. 

With advanced DNA repair techniques, Wasatch BioLabs’ proprietary library preparation methods preserve native cfDNA methylation integrity, enabling:

  • Unbiased insights free from bisulfite damage & amplification artifacts.
  • Accurate, comprehensive methylation analysis.

Preserving Native Methylation

Traditional
Methylation Array

Traditional Bisulfite
Sequencing

Direct Methylation
Sequencing

Methylation

Hydroxy-
methylation

Additional Base Modifications

Bisulfite
Conversion-Free

Approximate CpG Coverage

Additional Highlights

High-Throughput Multiplexing:

Analyze up to 24 samples per flow cell for scalable research and clinical applications.

Integrated Genomic Sequencing:

Simultaneously capture cfDNA methylation patterns and high-resolution genomic data for comprehensive insights.

Cell-of-Origin Precision:

Detect analyze complex cfDNA methylation signatures to optimize sensitivity and specificity.

Optimized Workflow:

Leverage streamlined protocols tailored for fragmented and degraded cfDNA.

Robust, Single-Molecule-Resolution Outputs

Designed to meet the needs of research and clinical assay development, dMS for cfDNA delivers customizable and scalable multi-omic solutions that advance biomarker discovery, epigenetic studies, and precision medicine. Additional highlights include:

A Paradigm Shift in Liquid Biopsy

Wasatch BioLabs’ dMS for cfDNA expands opportunities in biomarker discovery, multi-omics research, and clinical development by delivering comprehensive cfDNA insights without the limitations of traditional methylation technologies.

Expanded Biomarker Discovery
Optimized to maximize CpG coverage within the cell-free methylome, dMS enables the identification of methylation signatures that uncover cell-of-origin, regulatory roles, and disease mechanisms.
Accessible Multi-Omics Research
dMS seamlessly integrates into multi-omics workflows, simultaneously capturing methylation patterns and sequence variations in single runs for comprehensive insights into cfDNA biology.
Clinical Utility
dMS for cfDNA provides a powerful foundation for biomarker discovery and validation, supporting seamless transition to clinical assay development with Wasatch BioLabs’ targeted sequencing protocols.
Conservation Biology
Monitor methylation changes to assess health, adaptability, and stress responses in endangered species.
Precision Agriculture
Identify epigenetic markers to enhance crop resilience, yield, and stress resistance.
Developmental Biology
Investigate genome-wide methylation and sequence variations to uncover regulatory networks in cellular differentiation.
Epigenomic Aging Studies
Correlate methylation changes with genetic variations to refine biological aging models across species.
Sequencing purified cortical neuron-derived DNA with dMS enables precise quantification of cell-of-origin-specific DNA. Genomic DNA was extracted from primary motor neurons, fragmented to replicate cfDNA size profiles, and sequenced with dMS. Bioinformatic targeting of 4,152,224 CpG sites with cortical neuron-specific methylation signatures achieved >96% assignment accuracy.
Elevated levels of cortical neuron-derived cfDNA in blood correlate with Alzheimer’s disease (AD). cfDNA was extracted from blood samples from controls (n = 80) and AD patients (n = 61). Targeting cortical neuron-specific loci revealed significantly higher percentages of cortical neuron-derived cfDNA in patients with AD compared to controls.

WLB Case Study

cfDNA Cell Of Origin in Alzheimer’s Disease

This client case study demonstrates how dMS can precisely identify cfDNA cell of origin by analyzing unique, cell-specific methylation signatures. In neurodegenerative disorders like Alzheimer’s disease, dying neurons release cfDNA into circulation. Identifying the cell of origin may provide critical insights into disease mechanisms and progression. To learn more:

Making Direct Methylation Accessible

Wasatch BioLabs introduces MethylSeqR, a user-friendly R package that simplifies the transition from methylation arrays to dWMS. MethylSeqR utilizes proprietary .CH3 files, which compress data by up to 95%, streamlining both analysis and storage.

Seamlessly integrating with familiar pipelines, MethylSeqR makes advanced methylation analysis accessible to both newcomers and experienced users of nanopore sequencing, accelerating research and clinical applications.

MethylSeq Package Highlights

High Speed Performance:

Perform genome-wide methylation analyses in record time.

Simple, Powerful Workflow

Analyses in just three steps: Import Data, Run QC, and Analyze.

Efficient Storage

Compress 20 GB outputs to 1 GB, optimizing storage and transfer.

Optimized Memory

Process large-scale tasks seamlessly with on-disk database support.

(A) Positional Summary

(B) Summaries By Region

Accessing Familiar Data Views, In Seconds

Methylation summs by position, CpG Island
Differential methylation by region, read, position
Sliding window methylation analysis
Multiple quality control functions

Specialized offerings in our next-generation Biolab

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