CAMBRIDGE, England — biomodal, an omics-based life sciences technology and analytics company, has published a study in Nature Communications Medicine demonstrating that combining methylation and hydroxymethylation biomarkers can significantly improve the early detection of colorectal cancer through liquid biopsy.
The research highlights the performance of biomodal’s proprietary duet multiomic technology, delivered through its duet evoC solution, which enables 6-base genome sequencing. Unlike conventional approaches that collapse epigenetic signals into a single “modified cytosine” readout, the platform distinguishes between two functionally distinct markers, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), in cell-free DNA.
In the study, cell-free DNA samples from treatment-naïve colorectal cancer patients were analyzed and compared with samples from healthy controls. By integrating separate measurements of 5mC and 5hmC, biomodal’s models achieved a diagnostic accuracy of 95% for stage I colorectal cancer, with an area under the curve of 0.95. This performance substantially exceeded that of conventional methods, which produced an AUC of 0.66 using a conflated modified cytosine signal.
The analysis also revealed that nearly half of the genomic regions studied showed activation during disease progression. Early-stage cancers exhibited increased levels of 5hmC, while late-stage cancers showed decreased 5mC, underscoring the potential of hydroxymethylation as a sensitive biomarker for tracking disease development and progression.
“We know that earlier cancer detection is critical to improving patient survival, yet most of today’s methods fall short,” said Robert Osborne, biomodal’s Senior Vice President, Research and Development and lead author of the paper. “With our 6-base approach, we have demonstrated that by separately measuring and integrating both methylcytosine with hydroxymethylcytosine changes, we can capture biological signals that were previously hidden, opening the door to more sensitive, accurate, and informative liquid biopsy testing.”
Colorectal cancer is the second-leading cause of cancer-related deaths worldwide. While survival rates can exceed 90% when the disease is detected at stage I, most patients are still diagnosed at more advanced stages, when treatment options are more limited. The findings suggest that incorporating hydroxymethylation data alongside existing methylation and mutational signatures could meaningfully advance early detection and improve patient outcomes.
“Changes in DNA methylation patterns are among the earliest alterations observed in cancer cells, making them useful as biomarkers across oncology applications, from detection to monitoring treatment response,” said Prof. Sarah-Jane Dawson, clinician scientist at Peter MacCallum Cancer Centre and Centre for Cancer Research University of Melbourne. “biomodal is equipping the research community with more precise tools to interrogate biological changes at their earliest molecular stages, as well as to translate those findings into developing next-generation diagnostics and therapies in oncology and beyond.”
