Mendelspod Podcast

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For years, proteomics was described as the missing layer of biology. Why missing? Because measuring proteins at scale turned out to be vastly harder than sequencing DNA.
That may finally be changing.
In today’s episode Theral speaks with Dr. Yan Zhang, President of Proteomic Sciences at Thermo Fisher Scientific, about the rapid evolution of large-scale p…

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

This is a free preview of a paid episode. To hear more, visit www.mendelspod.com

On today’s show, a fascinating discussion about digital twins for medical research— leading to the 64 million dollar question of how much of the current AI wave in healthcare may eventually prove real.
Drawing on her background in cancer research and now as CEO of Concr, Dr. Irina Babina joins us to argue that the future of oncology may depend less on g…

An inventor of Solexa sequencing by synthesis has a new idea.
On today’s show, Sir Shankar Balasubramanian revisits the accidental origins of Solexa sequencing, born not from a sequencing project at all, but from curiosity-driven experiments watching DNA polymerase at work. What followed helped transform DNA sequencing from a specialized pursuit into a routine engine of modern biology. But as Shankar makes clear, the biggest surprise may not have been genomics itself—it was how next-generation sequencing became a universal readout for biology, powering everything from single-cell and spatial biology to entirely new ways of probing molecules and mechanisms.
Our conversation then turns to his latest venture, Biomodal, and the emerging world of 6-base sequencing. Shankar explains why distinguishing 5mC and 5hmC matters, and how six-base sequencing may improve early cancer detection. 6-base sequencing could also aid researchers in the exciting frontier of neurobiology.
As always with great scientists, the story widens beyond any single technology. Shankar closes by reminding us that discovery follows better measurement. As our tools improve, biology will continue to surprise us.
“That is what research is. It’s stepping into the unknown,” he 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

You’ve heard of 5-base genomics. How about 6-base? It turns out that separating 5-methylcytosine (mC) and 5-hydroxymethylcytosine (hmC) is pretty important.
Peter Fromen has had a front-row seat to the evolution of sequencing, from the rise of high-throughput genomics at Illumina to long-read technologies at PacBio. Now, as CEO of Biomodal, he’s focused on integrating genetics and epigenetics into a single workflow—and showing that the regulatory layer of the genome may be where the next breakthroughs lie.
Chapters:
0:00: Why epigenetics needed a reset12:07 The colorectal cancer study and early detection signal16:41 Building the 6-base ecosystem21:23 Commercial traction and the road to the clinic
In today’s program, Fromen explains why distinguishing between mC and hmC changes how we read biology. Biomodal’s recent colorectal cancer study begins to demonstrate that value in practice.
“We ultimately ended up generating an AUC of 95%,” he says, describing early-stage detection results that point to the power of combining both signals.
More broadly, he frames hydroxymethylation as an early indicator of disease.
“hmC is essentially the canary in the coal mine for early disease detection.”
We also discuss the practical side—what a 6-base workflow looks like in the lab and where the company sits commercially as it pushes toward clinical validation.
Will this be the new standard for how we read biology?


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