Mendelspod Podcast

For decades, biology has been driven by the powerful notion that if we could sequence enough genomes, transcriptomes, epigenomes, then we could finally explain the cell. On today’s show, Gary Schroth, the Chief Scientific Officer at Cellanome, argues that something essential was still missing.
Schroth spent nearly two decades at Illumina helping build the sequencing revolution. He has now joined Cellanome to pursue an expanded vision of biology that connects transcriptomics with live-cell imaging. Our conversation centers around two newly released preprints describing the company’s platform and its application to CRISPR screening, where imaging and transcriptomic data are explicitly linked in the very same cells.
“What we show in a few examples in both papers,” Schroth explains, “is that it’s the combination of transcriptome information and imaging information that really gives us the complete story of what that cell is doing.”
That idea—linking what researchers literally see under the microscope with the molecular state of the exact same cell—emerges as the core concept of the interview. Rather than treating imaging and transcriptomics as separate measurements, Cellanome brings them together in a longitudinal workflow where cells can be observed alive over time and then profiled at the transcriptomic level.
“Sequencing has certainly taught us a lot about cells and sort of the parts list inside cells,” he says. “But it doesn’t really explain biology.”
Will this be the next phase of post-genomic biology where the field moves beyond static snapshots toward directly observing cellular function as it unfolds?


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Today on the show, we’re discussing a new study just presented at ASCO 2026 that could change how chemotherapy decisions are made for a large group of breast cancer patients.
During ASCO we spoke with Phil Febbo, Chief Scientific and Medical Officer at Veracyte, and John Leite, the company’s Chief Commercial Officer, looking at the results from the OPTIMA study, a large prospective trial involving roughly 4,500 patients with clinically high-risk ER-positive, HER2-negative breast cancer. The study found that about two-thirds of these patients could safely avoid chemotherapy when treatment decisions were guided by the Prosigna test.
“What the Optima study shows definitively is that those women with low Prosigna score do not benefit from chemotherapy,” Febbo explains. “They get all the side effects… without any benefit.”
The data generated favorable attention at ASCO. The study produced prospective level 1A evidence, the highest standard for predictive testing, and addressed one of the central problems in breast cancer care: determining which patients actually benefit from chemotherapy and which patients may be exposed to toxic treatment unnecessarily.
Our show also looks at the broader evolution of molecular diagnostics in oncology. Prosigna runs on whole transcriptome sequencing, creating opportunities not only for current clinical decision-making, but also for future translational research into tumor biology and treatment response.
“We need the full complement of the transcriptome to understand what is the faulty circuitry and how do we shut it off therapeutically,” Leite says.
Veracyte has moved quickly from clinical validation to rollout. The company already has the assay prepared for U.S. launch immediately following the ASCO presentation. If only it worked out this way every time. It’s the kind of direct through-line between biology, clinical evidence, and improvement of human life that molecular diagnostics companies strive for each year.
Note: For more in-depth discussion on the OPTIMA study and the launch of Prosigna, sign up for an upcoming webinar at GenomeWeb here.


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For years, precision oncology has largely been discussed through the lens of breakthrough drugs. But there’s another story running underneath modern cancer care: the quiet rise of companion diagnostics. These tests are increasingly deciding who receives those therapies in the first place. In many cases, the real bottleneck is no longer discovering a drug target. It’s building a reliable system for identifying the right patient at the right moment in the disease. That challenge sits at the center of this conversation with Rita Shaknovich, Chief Medical Officer for Life Sciences and Diagnostis, and Karina Kulangara, Associate Vice President of R&D in Companion Diagnostics at Agilent Technologies.
Agilent has always had a major role in this field. Rita and Karina explain how companion diagnostics evolved from the original Herceptin test into a vision for a much broader ecosystem spanning pathology, automation, regulation, and global clinical deployment.
We dive into Agilent’s recent FDA approval expanding PD-L1 IHC 22C3 PharmDx into ovarian cancer, a development both guests describe as particularly meaningful given the historically poor outcomes associated with the disease. As Rita puts it: “Precision medicine is based fundamentally on scientific truth . . . it brought real results for patients. It brings better survival for patients, fewer side effects from the medication.”
Karina offers one of the clearest explanations we’ve heard for why immunohistochemistry or IHC has endured so long in modern oncology. “It’s the ability to detect protein biomarker in the spatial context of the tissue,” she explains, emphasizing that location and cellular context can fundamentally shape how therapies work.
What emerges is a picture of precision oncology that is becoming less exotic and more routine. We’re talking not just new drugs, but an entire clinical and technological infrastructure which is designed to match therapies to biology more effectively and over time.


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Dr. Eric Green returns to Mendelspod in a new role: Chief Medical Officer of Illumina. After more than three decades at the National Human Genome Research Institute, where he helped guide genomics from research initiatives to clinical reality, he now joins one of the industry’s most influential companies at a moment when the field is expanding beyond DNA alone.
Green takes us on a tour around the world of multi-omics, which he says is not a branding exercise but a practical response to the limits of sequence data by itself. Genomics remains foundational, but many clinical questions require additional layers of biology, including RNA, epigenomics, proteomics, and single-cell analysis. As he puts it, “DNA sequence alone may not reveal it.”
The discussion highlights rare disease as one of the clearest examples. Genome sequencing can solve roughly half of suspected cases, Green notes, but many patients remain undiagnosed because the relevant signal may lie in RNA splicing, epigenetic regulation, structural variation, or downstream protein effects. In those settings, multi-omic approaches can provide the missing evidence needed to move from uncertainty to diagnosis.
In oncology, the challenge is different. Cancer genomes can be highly complex and heterogeneous, making it difficult to distinguish driver events from background noise. That is one reason why researchers and clinicians are increasingly incorporating methylation markers, transcriptomic data, and proteomic signals into early detection, disease sub typing, and monitoring strategies.
Green also emphasizes that the next bottleneck may be less about generating data than interpreting it. “The human brain is not going to be the thing that’s going to crack this nut,” he says. “It’s going to be AI and computational biology.”
The result is an overall picture of where the field may be headed as we go from genomic medicine to a broader molecular medicine with multiple data types that will improve diagnosis, stratify disease, and guide care worldwide.


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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…