Separating Epigenetic Signals Improves Early Cancer Detection with Rob Osborne, Biomodal

We’ve gotten very good at reading DNA. We’re just beginning to understand how to read its state.On today’s show, Rob Osborne, Senior Vice President of R&D at Biomodal, discusses new evidence that separating two epigenetic marks—5-methylcytosine and 5-hydroxymethylcytosine—can improve early cancer detection from liquid biopsy. In a recent Nature Communications Medicine study, his team showed that analyzing these signals independently in circulating DNA significantly enhanced detection of Stage I colorectal cancer compared with approaches that combine them.The advance does not require new sequencing hardware. Biomodal’s approach uses a sample preparation kit compatible with existing platforms, paired with bioinformatics tools, potentially lowering the barrier to adoption while expanding the information content of standard sequencing workflows.The underlying insight is biological as much as technical. Most methylation assays collapse 5mC and 5hmC into a single signal, masking early transitions in gene regulation. Osborne describes this as “squishing them into one output,” a simplification that can obscure meaningful changes in disease onset and progression.By separating the signals, the study identified patterns that emerge earlier in tumor development, offering a more sensitive window into disease biology.But the deeper message of the interview is that this work may only scratch the surface. “I think that we’re just at the beginnings of really understanding this biology,” Osborne says. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe