UMBS-seq preserves DNA integrity while maintaining accuracy for cancer biomarker detection in liquid biopsies and tissue samples.
A novel methylation analysis method called Ultra-Mild Bisulfite Sequencing (UMBS-seq) has been developed to overcome long-standing limitations in cancer DNA methylation testing, according to research published in Nature Communications.
The method, initially developed by researchers at The University of Chicago and exclusively licensed to Ellis Bio Inc, addresses key problems with existing methylation sequencing technologies that either damage DNA samples or produce inconsistent results.
Traditional bisulfite sequencing has served as the gold standard for studying DNA methylation patterns, which are critical for cancer detection and treatment monitoring. However, the harsh bisulfite reaction often fragments DNA, leading to bias, poor recovery, and inaccurate methylation estimates. These limitations particularly affect analysis of short, delicate DNA fragments found in liquid biopsies or formalin-fixed tumor samples.
Newer enzyme-based approaches like enzymatic methyl-seq (EM-seq) avoid DNA damage but tend to have complex workflows and produce higher false positives, especially with low DNA inputs.
Re-engineered Chemistry Preserves Sample Integrity
The University of Chicago research team, led by professor Chuan He, re-engineered the bisulfite chemistry by fine-tuning the bisulfite formulation and reaction conditions. This approach achieved nearly complete cytosine conversion under ultra-mild conditions while preserving DNA integrity.
In comparative evaluations, UMBS-seq outperformed both conventional bisulfite and enzymatic sequencing methods across major performance metrics:
- Higher library yield and integrity
- Improved library complexity and better genomic coverage
- Exceptional conversion efficiency and highly accurate DNA methylation calls
- Streamlined workflow that is simpler and faster than enzyme-based conversion methods
When applied to human cell-free DNA samples used for non-invasive cancer diagnostics, UMBS-seq preserved DNA integrity and generated more complete coverage of cancer-related methylation sites than leading commercial kits, according to researchers.
“With UMBS-seq and the SuperMethyl Max kit that Ellis Bio developed based on UMBS, we can now read cancer’s epigenetic code without destroying the very few and precious molecules we need to study,” says Ruitu Lyu, incoming chief technology officer at Ellis Bio and co-author of the UMBS-seq study, in a release. “It’s a practical, scalable solution that could accelerate the clinical use of methylation biomarkers for early detection and personalized therapy.”
Commercial Availability Planned
Ellis Bio plans to make the method commercially available to cancer diagnostic test developers early next year through its SuperMethyl Max kit. The company currently operates an early-access program for the UMBS-based product.
DNA methylation analysis is crucial for cancer research and diagnostics because abnormal methylation patterns are a hallmark of cancer. These patterns can turn tumor suppressor genes off or activate cancer-promoting oncogenes in tumor cells. They also show promise for early cancer detection, monitoring treatment response, and matching patients to precision therapies.
The researchers envision UMBS-seq becoming a new standard for DNA methylation sequencing in both research and diagnostic settings, enabling more sensitive, reproducible, accurate, and cost-effective analysis of epigenetic changes in cancer applications.
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