Today we take a pretty comprehensive look at genomic testing in practice with Damon Hostin, Head of Market Access, Clinical Solutions at Illumina. Damon brings a rare perspective to this conversation. He’s been in the field since the Celera era, when sequencing was helping define modern genomics, and he’s also worked on the front lines in a large community health system, CommonSpirit Health. At Illumina, he speaks regularly with payers and other stakeholders.

Across oncology, rare disease, reproductive health, and pharmacogenomics, Damon describes a field that has clearly moved into standard of care in key areas—but is still very much in the phase of identifying the “eligible but under-tested.” Adoption is real, but it’s incomplete.

Chapters:

0:00 Genomic medicine arrives4:51 Genomics, imaging, and the EMR11:23 Oncology—from diagnostics to decision-making18:16 Rare disease and reproductive genetics28:51 The lifetime value of a genome36:03 Cost, quality, and what a genome is

A central idea running through the podcast is that the genome is no longer a one-time diagnostic. Its value compounds over time as databases grow, variants are reinterpreted, and new therapies emerge.

At the same time, even the basic notion of what a “genome” is, is beginning to shift. With the rise of multi-omic data—transcriptomics, proteomics, methylation—the question is no longer just cost per genome, but what kind of biological insight we’re actually measuring. “A genome isn’t a genome isn’t a genome,” Damon says.

He ends with a line that neatly reframes the entire debate around cost: “When you look at the cost of healthcare . . . the cost of the genomics is almost nothing.”

Genomic medicine is here. We’re now wrestling with how to scale it, how to use it earlier, and how to make it part of the everyday infrastructure of care.

Note: For more discussion and analysis on this topic, check out this upcoming Virtual Roundtable Discussion at GenomeWeb.

In this conversation, Fei walks us through how Slide-tags—now commercialized as Takara Bio Trekker technology—set out to close that gap. Instead of mapping gene expression onto a grid, his team flipped the problem: barcoding the cells in place, then reading them out with single-cell sequencing. The result is something closer to a GPS system for cells.

What this unlocks is not just better maps, but better biology. Better questions. In cancer, Fei describes the discovery of local immune “circuits” that determine whether tumors respond to immunotherapy. And more broadly, spatial data turns tissue itself into a kind of experiment itself. Is this the biology of the future? “The spatial context is a natural experiment that has happened.”

Chapters:

0:00 The problem: structure vs gene expression1:36 A GPS for cells8:59 Immune circuits and cancer response20:04 Tissue as experiment26:24 New questions for biology

Across applications, Fei emphasizes that the real shift is conceptual. Spatial biology is not just about adding location to sequencing. It’s about learning how to ask new questions—ones that treat cells not as isolated units, but as participants in research.

But beneath the market excitement and the GLP-1 headlines, something more interesting is going on. A field that for years seemed technically promising but perpetually constrained is becoming wide open.

To see into that open terrain, we’re joined by Charlie Johannes, founder of EPOC Scientific and president of the Peptide Drug Hunting Consortium, along with Tomi Sawyer, a founder of the Consortium and founder of Maestro Therapeutics. We asked them for a high-level look at a field being reshaped by advances in chemistry, screening, delivery, and by a growing sense that peptides may be uniquely positioned to open up biology that other modalities have only partly been able to reach.

And yet both are clear: the field is not mature. AI is accelerating biology, which still depends on existing knowledge. Prediction remains limited, especially with non-natural chemistry. And the core challenge may now be human—how to turn an overwhelming amount of data into real innovation. As Johannes puts it, “Turning knowledge into innovation is the real challenge.”

Chapters:

1:31 Why peptides are suddenly hot again6:10 Between small molecules and biologics10:14 Oral delivery, screening15:45 AI, automation, and the limits of prediction32:17 The Consortium and where the field is heading

This is not a finished revolution—it’s a launch. The field, Sawyer says, is “in the Artemis II rocket right now heading towards the moon.” The peptide story is now much bigger than obesity drugs. Where does the field stand today? What has changed, and what remains difficult?

This episode is the first in a new partnership between Mendelspod and Peptide and Protein News, a media platform covering peptide and protein drug development. You can see what they’re up to at peptideandprotein.com.

* 0:00 A long journey inspired by PCR

* 7:20 What is sequencing by expansion?

* 14:00 On scale and accuracy

* 19:40 Multi-omics vision?

* 24:40 What will be the killer app?

* 30:00 Biggest challenge for launch

Kokoris recounts the long path from co-founding Stratos Genomics in 2007 to Roche’s acquisition in 2020, when his team’s “wildly ambitious chemistry” finally found its match in Genia’s high-density nanopore platform. “Our approach to efficiently sequencing DNA,” he explains, “is to not sequence DNA. We rescale the problem—expand the molecule about 50-fold—so we can read it with much higher signal-to-noise.”

The result is astonishing speed. Working with the Broad Institute and Boston Children’s Hospital, SBX delivered whole-genome results in under four hours, with the sequencing step itself taking only about 15 minutes. Kokoris attributes the achievement to a confluence of chemistry and compute.

SBX’s duplex mode achieves Illumina-level accuracy (F1 > 99.8 %) while maintaining single-molecule simplicity. Its tunable flexibility lets small labs run a handful of samples in hours or large centers run thousands per day. Kokoris describes it as a technology built on impatience and rule-breaking, designed to give scientists options they’ve never had.

Looking ahead to the 2026 research-use launch, he’s characteristically bold:

“For me, success means SBX becoming the new standard in sequencing. Innovation can’t stop—it has to keep evolving, because biology is complex and we’ve got a lot more to do.”

This show was originally published Nov 11, 2025.

That question opens today’s interview with Steve Austad, Distinguished Professor at the University of Alabama at Birmingham and one of the leading thinkers in the biology of aging. It quickly becomes clear why he’s been such an important voice in bringing aging research from the margins into the center of science. As he puts it, the field was once “where scientists went to die,” but with modern genetic and molecular tools, it has become one of the most active areas in biomedicine.

Steve’s approach, laid out in his book for the empiricist (I’m an amateur), Methuselah’s Zoo, is deceptively simple: look at the animals. From birds and bats to clams that live for centuries, he shows that lifespan follows a clear evolutionary logic. Safer, more stable environments favor slower aging. “If it’s unstable and unsafe… it makes sense… to reproduce fast,” he explains, while protected environments allow organisms to invest in long-term maintenance. It’s a framework that turns curiosity into theory—and theory into something testable.

Chapters:

1:31 Where scientists went to die4:11 The opossum problem8:00 Air, land, sea14:23 The longevity quotient33:30 Not forever, just longer

What makes Steve such a compelling guide is his tone. He’s low-key, almost amused at times, but unwavering on the science. Aging, he reminds us, isn’t programmed for our benefit—“evolution does not care how long you live.” That doesn’t mean we can’t intervene. The field is now moving into human trials, even if key tools like aging clocks are still imperfect. He has little patience for talk of immortality—calling it “completely delusional.” Still, he’s optimistic. Adding a decade or two of healthy life—not forever—is the goal today.

Joining us on the program are Chris Hourigan, Director of the Fralin Biomedical Research Institute Cancer Research Center (DC) at Virginia Tech, bringing the academic and clinical AML lens, and Gary Pestano, Chief Scientific Officer at Biodesix, offering the industry and diagnostic development perspective.

Hourigan reminds us that MRD itself isn’t new. What was missing were the tools. From counting cells under a microscope to flow cytometry and now highly sensitive molecular techniques including droplet digital PCR, MRD has evolved into a quantitative, actionable signal.

Coming from the side of commercializing and scaling assays, Pestano underscores the central challenge of distinguishing meaningful signal from background noise. “There is a lot circulating in our blood. The key is what is meaningful, what is not meaningful,” he explains. Sensitivity alone isn’t enough. Target selection, bioinformatic filtering, validation at scale, and real-world reproducibility all determine whether MRD can truly guide care.

The field is very much still work in progress, say both.

Looking ahead, they point toward quantification as the next frontier. MRD is no longer just about detecting what remains. It’s about deciding what happens next.

“We’ve been talking about MRD as if it’s a binary concept” says Hourigan. “I can imagine in the future, there’s going to be windows, and we will tune therapy to what comes next.”

Thank you to Bio-Rad for sponsoring today’s show. Bio-Rad is your trusted partner for absolute quantification and reproducible results in oncology research. Bio-Rad helps you move from data to confident decisions. Learn more at bio-rad.com/oncology.

For two decades, tests like Oncotype DX have helped oncologists decide which early-stage breast cancer patients should receive chemotherapy. But those tools were designed mainly to predict early recurrence, leaving physicians with far less clarity about the risk that cancer might return years later.

For today’s program, George Sledge, Chief Medical Officer at Caris Life Sciences, discusses new findings from the TAILORx trial showing how multimodal AI—combining molecular sequencing, digital pathology, and clinical data—can improve long-term prediction of breast cancer recurrence.

Sledge explains that breast cancer recurrence may actually reflect two different biological processes unfolding over time. Molecular signals captured through RNA analysis appear most informative for predicting recurrence in the first five years, while computational analysis of digital pathology images becomes especially powerful for predicting recurrence later in the disease course.

“The best results come from looking at multiple omic levels,” Sledge says, describing a shift away from single biomarker tests toward integrated biological analysis.

Theral speaks with Sudhakaran Prabakaran, computational biologist at Northeastern University and founder of NonExomics, about his provocative new book, “Eclipsed Horizons: Unveiling the Dark Genome.” Drawing on his lab’s work cataloging more than 250,000 non-canonical proteins, Prabakaran argues that regions outside traditional gene definitions are constantly generating novel open reading frames—previously unrecognized proteins that may shape adaptation, speciation, and disease.

Chapters:

(00:00) Identical Genomes, Wildly Different Fish

(04:00) The Dark Proteome Wakes Up

(10:00) Protein Pop-Up Shops

(20:00) Homo Minimus and the Space Thought Experiment

(30:00) Precision Medicine Beyond the Exome

From rapidly diversifying cichlid fishes to human accelerated regions (HARs) of the human genome linked to schizophrenia, he makes the case that protein birth and death is continuous, cheap, and exploratory. In his framing, the “dark genome” functions less like debris and more like a flexible evolutionary sandbox—capable of producing latent biological parts that can be deployed under stress or even extreme environments like spaceflight.

The book goes beyond ENCODE’s demonstration of activity and asks what that activity is for, crossing into that taboo in biology, teleonomic analysis. Weaving together proteomics, evolutionary biology, information theory, and even speculative extensions into space biology, Prabakaran suggests that genomes may be structured not just to preserve past adaptations, but to enable future ones.

For those of you staying put on the ground, the implications are very tangible for precision medicine. His company NonExomics is using non-canonical protein signatures to stratify cancer patients and refine difficult diagnoses, arguing that the next wave of biomarkers may lie outside the exome.

Provocative? Certainly. Grounded in emerging proteomics tools and real clinical cases? Also yes. This conversation probes directly into that mysterious future of biology.

That’s Stephen Kingsmore, president and CEO of Rady Children’s Hospital (he just announced his retirement), explaining the impact of a new genome mapping technology from Illumina.

Whole-genome sequencing has transformed diagnosis, but some of the hardest pediatric cases persist because the structure of the genome has remained difficult to resolve. Today on Mendelspod, we cover Illumina’s newly launched proximity mapped reads, showing how long-range genomic context can be captured directly on existing Illumina sequencers and integrated into the lab workflow. The conversation traces how this added structural clarity is already improving diagnostic confidence and, critically, enabling highly precise n-of-1 therapies such as antisense oligonucleotides (ASOs).

Olivia Kim-MacManus, a pediatric neurologist and ASO trial leader, shows how the new diagnostic precision directly feeds therapeutic design.

“All of these genetic therapy approaches hinge on precise diagnostics,” she notes, emphasizing that allele-specific and haplotype-aware targeting is essential for ASOs and other emerging gene-based interventions.

From the product and workflow side, Ali Crawford joins us as Senior Director of Science Research at Illumina, detailing how the technology works without requiring new instruments or complex workflows, eliminating the need for separate library preparation steps.

“You just order the kit and go,” she says, highlighting how preserving spatial information on the flow cell unlocks variant calls and structural insight that were previously inaccessible with their standard short-read sequencing.

When genome structure comes into better focus, treatments are no longer theoretical.

CareDx is a company on the move. For years, they have been a bellwether in molecular diagnostics. Their early bet on gene expression testing in transplant medicine, their bruising fight over Medicare coverage, and their pivot into cell-free DNA monitoring have all reflected the growing pains of precision medicine itself.

Now, under CEO John Hanna, the company looks less like a single-test diagnostics firm and more like a clinical ecosystem.

Hanna brings an unusual vantage point. He began his career in health insurance before moving into molecular diagnostics—giving him insight into both innovation and reimbursement. That dual perspective shaped CareDx’s recent evolution: focus tightly on a defined clinical niche—transplantation—while expanding horizontally into the tools, software, and services that surround it.

Today, CareDx operates across three segments: lab products (including high-resolution HLA typing kits using PCR, NGS, and nanopore), a growing software and patient solutions business, and its flagship genomics portfolio led by AlloSure, its donor-derived cell-free DNA assay. What distinguishes the company now is its “solution selling” approach—engaging transplant centers not just with a test, but with workflow software, quality reporting tools, specialty pharmacy, and EMR integration.

“Our solution selling strategy is working,” he says today.

At the scientific core remains the effort to replace invasive biopsies with molecular monitoring. AlloSure’s innovation—detecting donor-derived cell-free DNA without requiring donor genotyping—made routine blood-based rejection monitoring scalable. Yet adoption is not purely technical.

“The biggest challenge with our space is building belief that molecular testing can replace tissue biopsy.”

Clinician education, clinical trials, and guideline inclusion remain central to shifting standards of care. CareDx has leaned heavily into this, hiring medical leadership specifically to translate data into practice. The company is also layering AI on top of its molecular assays. AlloSure Plus integrates genomic results with EMR-derived clinical variables to generate a rejection risk score. CareDx’s operational mantra has been to put the burden of complexity on the company, not the clinician.

In this episode of Mendelspod, we return to the kind of ambitious, shared genomics project that helped define the field a decade ago. The Global Parkinson’s Genetics Program (GP2) has now genotyped more than 100,000 participants worldwide, with roughly one third of samples coming from historically underrepresented populations. That scale and diversity are already reshaping how Parkinson’s disease is studied — and how it may eventually be treated.

My guests are Andrew Singleton, co-lead of GP2, and Ignacio (Nacho) Mata, a geneticist at Cleveland Clinic and founder of the Latin American Research Consortium on the Genetics of Parkinson’s Disease (LARGE-PD). Together, they describe how globally representative datasets are not a political aspiration, but a scientific necessity — especially in an era of precision medicine.

Singleton explains that studying Parkinson’s across populations doesn’t just broaden participation; it increases scientific power.

“The more we learn about individual populations, the more we understand about disease as a whole — and the more chances we have to come up with treatments for disease as a whole,” he says.

Mata brings a complementary perspective from years of building Parkinson’s genetics infrastructure in Latin America. He emphasizes that without inclusion in genetic and biomarker research, entire populations risk being excluded from the next generation of molecularly targeted therapies.

“If we don’t have our patients studied for genetics or biomarkers, then those patients will not have access to the new treatments,” he notes, adding that GP2 is designed to narrow rather than widen existing health disparities.

We explores how GP2’s open-science structure has been key to its success and could serve as a model for other global research projects. GP2 has invested heavily in training and infrastructure so that researchers around the world can lead analyses locally, rather than simply contributing samples.

As both guests make clear, this is only the beginning. With hundreds of thousands of samples committed and a new generation of globally distributed investigators, GP2 is laying the groundwork for biologically defined subtypes of Parkinson’s and for more precise diagnostics and disease-modifying therapies.

When genomics gets big enough — and inclusive enough — scale itself becomes a discovery.

On today’s show, Theral speaks with Yev Brudno, Associate Professor in the School of Pharmacy and also the Department of Biomedical Engineering at the University of North Carolina at Chapel Hill, about a deceptively simple technology that could dramatically accelerate manufacturing and lower the cost of cell therapies. Brudno’s lab works at the intersection of chemistry, biomaterials, and cell biology, with a focus on removing the manufacturing and scalability barriers that have kept powerful therapies like CAR-T out of reach for most patients.

At the center of the conversation is a dry, porous biomaterial sponge—developed initially by accident—that boosts viral transduction efficiency from roughly 10% to as high as 90% by forcing cells and viral vectors into intense, highly efficient contact. The sponge works across multiple delivery systems, including retroviruses, lentiviruses, AAVs, and even lipid nanoparticles, effectively functioning as a low-cost, scalable alternative to complex microfluidic systems. Brudno explains how this discovery reframes genetic modification as a physical- and materials-science problem rather than a purely biological one.

The discussion goes beyond mechanism into real-world impact. Brudno describes how these sponges—now commercialized for research use by Takara Bio USA—could compress weeks-long CAR-T manufacturing workflows into hours, enabling bedside or community-hospital cell engineering without the need for $100-million cleanroom facilities. The episode closes with a broader reflection on the future of cell therapy.

Once again, some of the most transformative advances might come from curious bench science and happy accidents rather than prediction alone.

0:00 From static snapshots to observing cell function in real time

4:45 Pairing phenotype with function like we never could before

7:30 Can see cell-cell interaction

19:40 Early applications

Rather than relying on static single-cell snapshots, the Cellanome platform enables longitudinal observation of live cells—tracking division, interaction, and function over time—before pairing those behaviors with transcriptomic and molecular readouts. As Gherardini explains, “This creates essentially a new data type where you observe cells over time… and then you can pair all of that functional information with the molecular readouts that you get from sequencing.”

For Spitzer, that shift fundamentally changes what can be known. Traditional approaches often force scientists to infer function indirectly, correlating phenotype measured in one experiment with behavior measured in another. With CellCage, his lab can finally measure both in the same individual cell.

“Now we have measured the function of the cell and the phenotype for the same exact individual cell,” Spitzer says, “and this allows us to really understand how those core characteristics are linked in a much more detailed way.”

For Spitzer, a major advance comes from observing cell–cell interactions as they unfold. Where previous methods could show proximity in a tissue section, they could not reveal outcomes. Using Cellanome, Spitzer’s team can now watch whether a T cell activated by a dendritic cell actually proliferates, produces effector molecules, or kills a tumor cell—and then trace those outcomes back to specific molecular programs. This has already revealed surprising heterogeneity within supposedly uniform cell populations, identifying rare but highly potent immune cells that would have been invisible in bulk assays.

Looking ahead, both guests see immediate applications in cell therapy development, target discovery, and functional CRISPR screening—areas where measuring what cells actually do matters more than what they merely express. We close with a sense that cell biology is entering a new phase—one where function, interaction, and time are no longer inferred, but directly observed, measured, and modeled.

In this episode, we talk with ElNaggar about the rapid rise of ctDNA-based monitoring and how it’s changing the very rhythm of cancer care. From Natera’s “tumor-informed” SignateraTM assay to its new “tissue-free” LatitudeTM test, the company is reshaping oncology around the molecular traces that cancer leaves behind.

“ctDNA-negative patients have an extremely low likelihood of showing disease on imaging,” he explains. “So rather than scanning every few months, we can tailor follow-up to when it’s actually needed—and spare the anxiety and cost that come with it.”

The conversation also covers Natera’s EmpowerTM hereditary cancer panel, which has expanded testing to all patients with ovarian and endometrial cancer, and a new Hereditary Cancer Alert program that nearly doubled testing rates among eligible patients. ElNaggar describes how hereditary and MRD testing now reinforce one another, helping clinicians catch missed cases and close the loop for families.

We finish with a look ahead: a future where ctDNA status becomes a staging element, where clinical trials are shortened by molecular endpoints, and where multi-omic assays—combining DNA, methylation, and protein—push oncology toward truly personalized medicine.

“We’re reaching the point,” says ElNaggar, “where staging won’t just be about pathology—it’ll be about biology.”

Note about trials mentioned:

IMvigor010 compared adjuvant atezolizumab to observation (surveillance) in an unselected muscle-invasive bladder cancer (MIBC) population

IMvigor011 prospectively randomized only ctDNA-positive MIBC patients to atezolizumab versus placebo

See all SignateraTM Publications here.

In this wide-ranging and genuinely mind-bending conversation, Alan Landay and Tom Blackwell make a compelling case that aging itself is finally becoming a legitimate—and testable—target of medicine.

For Landay, the path into aging biology began decades ago through HIV. Antiretroviral therapy transformed HIV from a fatal disease into a chronic one—but something didn’t add up. Patients were surviving, yet developing cardiovascular disease, neurocognitive decline, and metabolic disorders years earlier than expected. The immune system recovered on paper, but inflammation never fully resolved. That realization led Landay to view HIV as a model of accelerated aging, and to ask whether the same inflammatory processes drive aging in the broader population.

As he explains, “we realized that persistent inflammation was the driver—pushing comorbidities forward in time. That’s when HIV stopped being just an infectious disease and became a window into aging itself.”

Over the past decade, Landay has brought the full toolkit of systems biology to that question—proteomics, metabolomics, glycomics, microbiome analysis, and epigenetic clocks—to understand why some bodies grow frail while others remain resilient. A central theme is the gut: age-related changes in the microbiome weaken the intestinal barrier, allowing inflammatory signals to leak into circulation and quietly accelerate biological aging.

Blackwell approaches the same problem from the clinic. As a geriatrician, he sees that most people ultimately die from one of three conditions—heart disease, cancer, or dementia—and that aging is the common denominator behind them all. His bold question is not whether we can treat these diseases individually, but whether we can slow the biological aging process that gives rise to them. That question underpins his ongoing clinical trial testing tirzepatide, a GLP-1–based therapy, not for weight loss, but for its potential to slow aging itself. “

“There is no drug in the world proven to slow aging,” Blackwell says. “We haven’t proven this one either—but we’re finally running the experiment that can give us a real answer.”

At the heart of the discussion is a shared fascination—and healthy skepticism—around aging clocks and biomarkers. Both researchers are using advanced epigenetic and proteomic clocks, including the DunedinPACE measure, to track whether interventions truly change the rate at which people age biologically. The clocks are powerful, but not yet definitive.

The episode also explores how geroscience has moved from the fringe to the mainstream: NIH-wide initiatives, ARPA-H funding, repurposed drugs, and growing FDA openness to aging as a trial framework. Rather than chasing immortality, both guests emphasize healthspan—more years of mobility, cognition, and social engagement.

“Our vision isn’t to live longer in a nursing home. It’s having a lot more 98-year-olds who drive themselves to clinic, go on dates, and still love their lives,” says Blackwell.

The RNA revolution didn’t end with COVID. It’s only just beginning.

Today Theral is joined by Andrew Geall, co-founder and Chief Development Officer of Replicate Bioscience, to explore why self-replicating RNA may represent the next major leap in vaccines and therapeutics. While first-generation mRNA proved what was possible in a pandemic, Andrew argues …

Theral speaks with Aqib Hasnain, Product Lead at Mithrl, and Cheng Hu, co-founder and CEO of Technetium Therapeutics, about how scientists can go from AI generated insights to AI generated assets, from AI-driven fast science, to AI-driven fast drug discovery.

Aqib describes Mithrl as a virtual lab partner focused on shrinking the time between experiments by letting scientists interrogate their own data directly. One of the biggest lessons in building Mithrl, he says, was how much transparency matters. Biologists need to understand the methodology through and through, and this translates directly to how Mithrl works.

“Scientists need to be able to scrutinize and trace everything—because it’s their responsibility to make the next decision.”

Cheng explains Technetium’s vision of an “AI-driven hatchery of novel medicines,” using design-based, physics-guided approaches to move from target discovery to small-molecule hits in weeks rather than years as has been the case screening libraries of millions of compounds. Reflecting on the promise of AI co-scientists, he points to the industry’s biggest unmet need.

“There’s a very serious deficit of novel therapeutic targets and also a very serious deficit of novel chemicals.”

Together, the conversation explores how these two AI tools for target discovery and hit generation are beginning to reshape drug discovery workflows—and how a new ecosystem of services is developing that is redefining the field.

Ellman shares the deeply personal origin story behind Certis and explains why their models have changed lives. He discusses the company’s AI-driven predictive platform, now patented, that aims to double drug success rates and usher in truly personalized oncology.

Happy New Year 2026!

Udayan says the scale of adoption surprised even the team. “We said we wanted to be the front end of every sequencing technology. We’ve actually done that,” he notes, adding that more than ten applications now support short- and long-read sequencing.

What’s driving the momentum? Three things keep coming up from customers: true walk-away automation, the ability to run any chemistry on any sequencer, and major improvements in quality and cost. Labs without automation engineers can now “simply buy a kit and run software…without having to learn sample prep,” Udayan explains.

A standout story this year has been pediatric oncology, where whole-genome sequencing and hybrid-capture workflows have shown strong performance on Callisto. Customers such as Prinses Máxima Center and UMC Utrecht are using the platform across Illumina, Oxford Nanopore, Ultima, and other chemistries, achieving the sequencer-agnostic vision Volta set out from the start.

Looking ahead, Udayan sees sequencing as still early in its evolution and believes sample prep has vast room for innovation. “One platform to do Illumina, one platform to do Oxford Nanopore, one platform to do Ultima… long read, short read—we do it all,” he says.

In this debut conversation, Cellanome CEO Omead Ostadan traces his path from the early days of Applied Biosystems and Solexa to what he calls “the multi-omics of the cell.” He describes a breakthrough platform capable of observing living cells in real time, combining imaging, molecular analysis, and computation in ways that bring biology closer than ever to its native state.

“Our hypothesis,” says Ostadan, “is that you are now creating an environment that most resembles the natural environment in which these cells operate. Anything you’re measuring is much more likely to resemble what you’re going to see in real biology.”

Using what the company calls CellCage technology, the Cellanome R3200 system can isolate and sustain thousands of living cells or co-cultures—neurons with microglia, for instance—allowing researchers to track interactions, responses, and phenotypic changes over time. Ostadan believes this kind of structured, longitudinal, multimodal data will be foundational for the next generation of AI-driven biological models.

“The next leap in biology,” he says, “requires a fundamentally different mode of data. That has been our focus from the start—to generate data that most closely resembles what’s happening at the foundational basis of biology across all organisms.”

Now in full commercialization, Cellanome has multiple units installed in the U.S. and preparing for expansion into Europe and Asia. For Ostadan, who has helped bring multiple life-science platforms to market, this moment feels singular:

“I’ve never been as excited about the potential of a technology as I am about what we have at Cellanome,” he says.

Yet alongside this institutional upheaval, Green describes a scientific landscape moving at astonishing speed—from the maturation of genome editing and long-read sequencing to the rise of multi-omics and the accelerating push toward routine healthy newborn genome sequencing. He believes widespread newborn sequencing is no longer a distant vision but “within striking distance,” driven by global studies, new U.S. programs, and rapidly falling costs.

The conversation also explores the political pressures shaping genomics today, especially around the collection of heterogeneous genomic data and the cultivation of a diverse workforce. Green argues that scientists must learn to explain their work in human terms—as stories about patients and cures, not grants and budgets. He says it might also be a good idea to not use the “d” word (for example, “assortment” rather than “diversity”) in grants for now, silly as that is.

Despite the personal and institutional losses of the past year, Green remains committed to the future of U.S. biomedical science which continues to surge in the headlines each day. In a reference to Dickens, he says it is literally the best and worst of times.

Now entering what he calls “version 3.0,” Green sees his role as genomics evangelist, educator, and advocate—helping ensure that the momentum of genomic medicine continues even as the nation’s scientific infrastructure undergoes profound stress.

“I am officially on call to help rebuild the NIH… It’s very easy to destroy a place, and very hard to rebuild it.”

Catching a cancer relapse before any scan could see it is the ultimate goal for minimal residual disease or MRD testing. And it’s the promise behind Foresight Diagnostics, a Stanford spin-out co-founded by scientist Jake Chabon and oncologist David Kurtz who say they have arrived at “next gen” MRD testing. In this debut interview, Jake and Dave walk us through their journey from academic research to launching one of the most sensitive MRD tests on the market—one that’s already shaped new NCCN guidelines.

* 0:00 Origin story

* 4:45 What makes this “next gen?”

* 10:15 How do you get the leap in sensitivity

* 15:45 Already had an impact on NCCN guidelines

* 23:00 Launching lymphoma texting next year, then on to solid tumors

* 28:00 How will this change standard of care?

Jake explains how their novel PhasED-Seq technology, which tracks “phased variants”—usually two or three mutations on the same DNA molecule—enables unprecedented sensitivity, detecting cancer cells at levels as low as one part in 10 million. “It’s extremely unlikely to have two concurrent sequencing errors,” says Jake. “That’s functionally the core insight here.”

For Dave, who still treats lymphoma patients, the clinical need is personal. “Our goal is to treat patients until there are no more cancer cells in the body. So having a tool that tells you when there are no more cancer cells left is kind of our holy grail.”

Their MRD test, called Foresight CLARITY, launches first for lymphoma next year, with solid tumor applications in development. As their data have already begun to reshape the standard of care, Jake and Dave discuss a future in which MRD testing could come before PET scans—or even replace them.

“We want MRD testing to become the standard of care across all cancers treated with curative intent,” says Jake. With Foresight CLARITY already in three prospective trials and in NCCN guidelines, and a clear clinical need, that vision may not be far off.

Petter shares how a single lecture on natural killer cells pulled him into immunology, and how early twin studies convinced him that “our immune systems are shaped predominantly by non-heritable factors.” That insight drove him to study the earliest stages of immune development—when newborns leave a sterile environment for a microbial world that imprints their immune trajectories for life.

A major theme of the conversation is Petter’s insistence that immune responses cannot be understood by looking at cells one by one. As he puts it: “Cells don’t ever work in isolation, but historically we’ve always been studying them in isolation—and I think that’s fundamentally problematic.”

This systems view is now being partly enabled by Pixelgen’s spatial interactomics. Using their Proximity Network Assay, Petter’s group is finding that lupus B cells don’t just differ in protein expression—they differ in protein distribution, revealing organization patterns that classical flow cytometry cannot capture.

These spatial signatures may point directly to new, more precise therapies. Petter explains: “If there is a difference in protein–protein interaction or protein distribution that characterizes disease, then surely that indicates a dysregulation—and that is something we can target.” Instead of broad immunosuppression or depleting whole cell populations, future treatments could focus on the exact cell states driving autoimmunity.

Petter ends on an optimistic note: spatial interactomics won’t just help treat autoimmune disease—it may allow us to intervene earlier, even preventatively, as we learn how early-life immune disturbances set the stage for disease decades later.

To guide us, we welcomed two leaders at the center of this emerging field: Chirag Patel of Harvard and Gary Miller of Columbia University, fresh off organizing Genomics Meets Exposomics, a landmark meeting held at the Mendel Museum in Brno—the birthplace of modern genetics. In the same abbey where Mendel tended pea plants, genomics and exposomics researchers from Europe and the U.S. gathered for the first time to build a shared roadmap for understanding how genes and environment interact to drive disease.

In our conversation, Chirag and Gary explain why the genome alone can’t answer the biggest questions in human health. While genomics accounts for roughly 20% of complex disease risk, the remaining 80% lies in our exposures—pollutants, diet, geography, stress, microbes, medications, and more—and the fingerprints these exposures leave on our biology. Exposomics, as Gary notes, is about moving from studying one factor at a time to systematically measuring the thousands of signals that accumulate in our tissues and blood.

A major theme of the discussion—and the inspiration for our episode title—is Chirag Patel’s call for exposomics to follow the same playbook that transformed genomics in the early 2000s. Just as genome-wide association studies (GWAS) revolutionized how we identify genetic contributors to disease by moving beyond one-gene-at-a-time thinking, Patel argues that the field now needs exposome-wide association studies (EWAS) to systematically search for environmental drivers. “If we are to do an exposome-wide association study… we can now discover things that were missing,” he explains, shifting from narrow, candidate-factor approaches to broad, data-driven discovery.

Both guests describe a field gaining momentum thanks to better measurement technologies, large biobanks, geospatial data, and new analytic frameworks inspired by genome-wide association studies. They also speak frankly about the remaining hurdles. As Chirag puts it, one of the major challenges is not just correlating exposures with disease but determining what these findings mean for people: “There’s a number of questions that come after that…how do you modify it? Is it causal? How do we remove it from the population if it’s adverse?”

Gary, who has spent decades studying Parkinson’s and Alzheimer’s, explains how high-resolution mass spectrometry now allows researchers to see exposure signals that were invisible before—sometimes even in decades-old blood samples. And looking ahead, he offers a clear note of optimism about exposomics’ readiness for scale: “We can do this now. It’s a reality.”

For long-time Mendelspod listeners, the episode marks an inflection point. After fifteen years covering genomics and the multi-omic revolution, this conversation shines a light on the other half of human biology—the environment—and what may become the next major frontier in disease prevention, drug development, and precision health.

* 0:00 Long read sequencing changing clinical landscape

* 7:00 Long reads replacing older technologies

* 13:15 Agilent/PacBio partnership – speeding up adoption

* 16:00 Panels designed for short reads can be used for long reads

* 24:25 Democratizing access

Long-read sequencing—once prized mainly by researchers for its ability to resolve structural variants, repeat expansions, and complex genomic regions—has reached a point of technical and economic maturity that now makes it viable in the clinical setting.

“We can now see regions of the genome that were long considered dark matter,” says Shakhnovich. “That’s leading to improved diagnostic yield and, most importantly, better outcomes for patients.”

Agilent brings to this collaboration a long-standing foothold in laboratory testing. Its automated platforms and target enrichment chemistries are already embedded in many diagnostic laboratories worldwide. PacBio, of course, brings the power of HiFi long-read sequencing to the table. Together, the companies are demonstrating that technologies originally designed for short-read sequencing can be seamlessly adapted to long-read workflows.

“Panels that were designed for short reads can be used for long reads—essentially right out of the box,” explains Kingan. “It really just opens up a whole world of clinical applications immediately.”

By combining Agilent’s infrastructure and expertise with PacBio’s long-read innovation, the partnership is accelerating the integration of comprehensive, single-platform sequencing into patient testing. The result is a streamlined, cost-effective approach that reduces the need for multiple assays while providing richer genomic insight.

Adarsh began his career at Nvidia, long before the company became synonymous with AI. “What I learned there,” he recalls, “was that when you build a team around exceptional talent, deep passion, and empathy—especially empathy for your customers—everything else flows from that.” That lesson guides how Mithrl now builds tools for scientists drowning in data.

At the heart of Mithrl is a platform that takes scientists from raw data to biological insight in minutes, complete with automatic data cleaning, literature integration, and a conversational interface. Adarsh describes how one pharma team identified new biomarkers in 15 minutes—a process that would normally take months—and how another user avoided a costly error when Mithrl’s reasoning layer caught an incorrectly labeled sample.

Asked about the risk of losing “happy accidents” in a world of faster science, Adarsh pushed back:

“AI doesn’t eliminate the happy accident—it multiplies the opportunities for it. You can’t control luck, but you can create the conditions for it to appear more often.”

In closing, he offered a glimpse of what drives him:

“If we can accelerate the path from raw data to real discovery—from sequencing files to the next therapy—then we’ve done something far bigger than building software. We’ve built a partner for science itself.”

* 0:00 A long journey inspired by PCR

* 7:20 What is sequencing by expansion?

* 14:00 On scale and accuracy

* 19:40 Multi-omics vision?

* 24:40 What will be the killer app?

* 30:00 Biggest challenge for launch

Kokoris recounts the long path from co-founding Stratos Genomics in 2007 to Roche’s acquisition in 2020, when his team’s “wildly ambitious chemistry” finally found its match in Genia’s high-density nanopore platform. “Our approach to efficiently sequencing DNA,” he explains, “is to not sequence DNA. We rescale the problem—expand the molecule about 50-fold—so we can read it with much higher signal-to-noise.”

The result is astonishing speed. Working with the Broad Institute and Boston Children’s Hospital, SBX delivered whole-genome results in under four hours, with the sequencing step itself taking only about 15 minutes. Kokoris attributes the achievement to a confluence of chemistry and compute.

SBX’s duplex mode achieves Illumina-level accuracy (F1 > 99.8 %) while maintaining single-molecule simplicity. Its tunable flexibility lets small labs run a handful of samples in hours or large centers run thousands per day. Kokoris describes it as a technology built on impatience and rule-breaking, designed to give scientists options they’ve never had.

Looking ahead to the 2026 research-use launch, he’s characteristically bold:

“For me, success means SBX becoming the new standard in sequencing. Innovation can’t stop—it has to keep evolving, because biology is complex and we’ve got a lot more to do.”

In this episode, we talk with Dr. Andrew Farmer, Chief Scientific Officer and Head of R&D at Takara Bio USA, about the company’s remarkable evolution from a Japanese enzyme maker to a global innovator in single-cell and spatial biology. Farmer recalls, “We go way, way back to being a sake manufacturer a hundred years ago. And it’s through that business—realizing that sake is basically fermentation—that we could use that to do other interesting things in biology.”

* 0:00 Began as a sake manufacturer over 100 years ago

* 5:25 First kit for single-cell sequencing

* 11:10 Bought Curio Bioscience to bring in spatial omics

* 15:00 Returning to the level of the cell

* 26:40 The new “T-cell sponge”

He describes how Takara Bio introduced the first commercial single-cell reagent kit long before the current explosion of single-cell technologies: “The first single-cell reagent kit on the market was actually from us. That was in 2011, and even the Fluidigm C1 system was driven by our chemistry.”

The conversation then moves through Takara’s acquisition of Curio Bioscience, adding the Trekker and Seeker spatial platforms, which—remarkably—require no specialized instruments. Farmer explains how this simplicity could democratize access to spatial data and accelerate multiomic studies in cancer and drug discovery.

And for an ending twist, he introduces the “T-cell Sponge,” a porous hydrogel matrix that activates and transduces T cells in a single step—an innovation recently named one of The Scientist’s Top Innovations of 2025.

Dr. David Braxton, Chief of Molecular Pathology at Hoag Memorial Hospital in Southern California, has built a system where the answer is simple: the pathologist decides. At Hoag, reflex testing protocols automatically trigger genomic tests when certain cancers appear under the microscope—embedding precision medicine directly into the biopsy workflow.

* 0:00 How did you become an advocate for precision medicine?

* 5:50 What triggers the ordering of a genetic test?

* 12:00 Using national lab vs in-house

* 19:03 Which areas show most progress?

* 24:32 A fan of early cancer testing?

* 29:42 How digitized is your lab?

* 42:45 Moonshot? Treat CHIP

“We developed standardized operating procedures where if a pathologist sees certain types of cancers in certain states, they automatically order the genomic testing,” Braxton explains. “It’s all very formalized. We call it pathologist-initiated reflex testing—and it gets results into the medical record before the oncologist even sees the patient.”

Braxton talks about making genomic profiling routine in a community setting, the barriers that still slow precision medicine—education, reimbursement, regulation—and how digital pathology and AI are reshaping what pathologists can see and do. “The real value of digital pathology and AI,” he says, “isn’t necessarily helping pathologists do their jobs quicker or better—it’s going beyond what the human eye can see.”

Braxton offers a pragmatic, hopeful look at how community hospitals can lead the next phase of precision oncology. We discuss the increasingly used MRD testing and get Braxton’s thought’s on early cancer detection tests. In the end, he shares his “moonshot:” using molecular diagnostics to detect clonal hematopoiesis, a precursor state that silently increases risk for leukemia, heart disease, and other inflammatory conditions. “If you want to talk about the role of diagnostics in decreasing chronic conditions like heart attacks and cancer,” he says, “this is the moonshot—catching that silent killer early with molecular techniques.”

In this episode of Mendelspod, Krishna Morampudi, Associate Director for Product Management at Illumina, joins Theral to talk about the company’s recent definitive agreement to acquire SomaLogic and the new launch of Illumina Protein Prep, their new end-to-end proteomics solution.

0:00 On the acquisition of SomaLogic

4:30 Scoop: Illuminated Protein Prep just launched

8:00 Competitive edge

14:15 The larger multi-omics vision

Illumina’s new product can screen for 9,500 proteins using SomaLogic’s SOMAmer technology, with sequencing on NovaSeq and data processed through Illumina’s existing connected analysis platforms. According to Morampudi, the integration with Illumina’s NGS workflows gives researchers a competitive edge and lowers the barrier to proteomics adoption.

The product has already launched with early access customers, including large biobank studies such as UK Biobank through partnerships with Decode Genetics. Krishna notes that “the motivation to buy the company was really coming from working with those early access customers.”

With a vision to make large-scale quantitative proteomics standard in discovery research, Illumina is betting that SomaLogic’s scalable, high-throughput tech can eventually outpace long-established competitors.

“We’re starting with 9,500 proteins with lower CVs than Olink. Our ability to scale faster to the entire native proteome gives us a real advantage,” Morampudi says.

In the final segment, Morampudi connects the proteomics launch with Illumina’s broader multi-omics vision and outlines the potential for new biomarker discovery, PQTL analysis, and phenotypic insights.

On today’s debut interview with Truvian Health, CEO Jay Srinivasan lays out the company’s bold but grounded plan to radically decentralize blood testing. With over $150 million raised and a benchtop instrument already in FDA review, Truvian aims to run 34 lab-quality tests from just eight drops of blood—in under 30 minutes.

“Why does your blood have to t…

Premal Shah says that many companies in personal genomics have emphasized quantity over quality. Premal is the CEO of Myome, a company offering whole-genome interpretation built for the clinic rather than the consumer.

Shah says Myome was founded on the belief that more data isn’t better data. “Physicians don’t want a laundry list of genes,” he told us …

Dr. Stefan Green, who directs the Genomics and Microbiome Core Facility at Rush University, has been putting the instrument through its paces on challenging projects ranging from pathogen surveillance in Chicago to ultra-low biomass cleanroom samples for NASA. “PCR is both the greatest and worst invention of all time,” he says. “It’s empowered everything in molecular biology, but it introduces biases and artifacts. With iconPCR we finally have adaptive cycling that lets us stop at the right point for each sample.”

Joining him is Yann Jouvenot, Senior Director of Product at n6, who explains how the company designed iconPCR’s AutoNorm technology to take the guesswork out of amplification. “PCR is to genomics what the printing press was to knowledge,” he says. “But unlike a press, PCR doesn’t produce identical copies at cycle two and cycle twenty-five. With iconPCR we’re helping scientists cut cycles before artifacts creep in, which means more accurate data and a better chance for every molecule to be represented.”

* 0:00 “I wanted a device like this a decade ago.”

* 6:41 PCR, the greatest and worst invention

* 10:20 The “slope” method

* 18:00 Protecting small samples

* 28:45 Impact on research?

Together they paint a picture of a deceptively simple but transformative innovation: a thermocycler that adapts in real time, reduces artifacts, saves time and labor, and improves the quality of genomic data.

* 0:00 Squarely in the long read age

* 6:10 When short reads, when long?

* 9:20 Whole genome testing

* 15:00 Targeted long reads

* 19:40 Roche’s new technology

* 23:00 Multiomics: the bigger picter

* 26:50 “I love MRD!”

Our focus today is the economics of short reads versus long reads, the unexpected dominance of liquid biopsy, and why long reads are proving indispensable in cancer and rare disease diagnostics. He uses an illuminative metaphor.

“The genome is like a jigsaw puzzle. With short reads, you’re stuck with thousands of tiny sky-blue pieces—it’s ambiguous. With long reads, you get bigger chunks, and suddenly you can see where the pieces belong. That’s how you detect the real structural changes in cancer,” he explains.

Alex also dives into the new technology from Roche, weighing their disruptive potential. Beyond sequencing, he highlights the surge in multi-omics, particularly proteomics, and the gap between fast-moving diagnostics and available therapies.

“Diagnostics is now ahead in many ways. In MRD especially, we can double progression-free survival if we catch cancer’s return early. The question is, do we have enough therapies to act on all this new information?”

* 0:00 Success coming from a focus on rare disease

* 5:20 Why whole genome testing?

* 13:30 “No margin, no mission”

* 15:50 Acquiring Fabric Genomics

* 26:10 Bullish on healthy newborn screening

“We’ve been focused on solving the fact that it still takes, on average, five years for a child with a rare genetic disease to get a genetic test and an accurate diagnosis. That’s something we can now provide within weeks, if not days, if not 48 hours.”

On newborn screening, Stueland points to the GUARDIAN study at Columbia as a model: “What we’ve been able to find is a diagnosis in 3.2% of these otherwise healthy newborns. And the average age of diagnosis for those same conditions, in GeneDx’s 25-year history, had been 7 to 11 years. We’re now able to find them at birth.”

From shortening the time to diagnosis to embedding genetic testing in general pediatrics, GeneDx is showing what it looks like to deliver on the promise of genomics in everyday medicine.

Few founders get to build the future of genomics twice—Moran Snir is doing it a fourth time. After founding Clear Genetics and helping Invitae scale genetic services, she’s back with a new venture: Nest Genomics, a software platform aiming to make genomic care routine across U.S. health systems.

* 0:00 Founder of four genomic medical companies

* 6:55 When sho…

* Chapters:

* 0:00 What are PDx models?

* 6:30 Orthotopic experts

* 10:45 Success stories

* 18:45 Winning an AI patent

* 23:40 Business model

* 27:40 The future will be so different

Since then, Certis has become the orthotopic experts—placing patient tumors in the “correct place” inside mice to create more faithful cancer models. These avatars don’t just support research, they’ve helped extend lives. Peter tells the story of one patient who came to him simply hoping to live long enough to dance with his daughter at her wedding. Thanks to Certis’s avatars, he did.

Today, the company is pushing further. They’ve built a tumor bank nearly as large as the NCI’s and, most strikingly, just won a patent for their AI platform. “Patents in AI are rare,” Peter told me. “To us, this one isn’t just a legal win—it’s recognition that our predictive platform is novel and fundamental to how oncology will be done in the future.”

Ellman imagines a not-so-distant future where drug success rates could rise from 10% to 50%, creating a world where “standard of care gives way to truly personalized medicine.”

Sponsor:

* 0:00 New MRD and HRD testing

* 5:30 What has you excited?

* 9:32 Great numbers year after year - what’s your secret sauce?

* 16:00 “A long way to go” on physician education

* 20:15 Thoughts on DTC?

* 23:40 First test using AI

* 27:00 The decade ahead

Myriad has announced strong financials and a robust pipeline, including its first AI-powered test for prostate cancer launching in early 2026 and a proprietary minimal residual disease (MRD) test slated for mid-2026. “We’re still in the early innings of the golden age of genomics,” Raha said. “What excites me is taking a brand that’s well-known in our space and really having the company live up to its potential.”

In this wide-ranging conversation, Raha discussed what he sees as Myriad’s “secret sauce” for steady growth, the need for greater physician education—“we have a long way to go”—and his vision of combining genomics with imaging, proteins, and AI over the next decade.

“Success is not just the numbers,” he emphasized. “We can grow in the low double digits profitably, while being a company that patients, providers, and employees are proud to work with.”

* 0:00 Origin story

* 4:45 What makes this “next gen?”

* 10:15 How do you get the leap in sensitivity

* 15:45 Already had an impact on NCCN guidelines

* 23:00 Launching lymphoma texting next year, then on to solid tumors

* 28:00 How will this change standard of care?

Jake explains how their novel PhasED-Seq technology, which tracks “phased variants”—usually two or three mutations on the same DNA molecule—enables unprecedented sensitivity, detecting cancer cells at levels as low as one part in 10 million. “It’s extremely unlikely to have two concurrent sequencing errors,” says Jake. “That’s functionally the core insight here.”

For Dave, who still treats lymphoma patients, the clinical need is personal. “Our goal is to treat patients until there are no more cancer cells in the body. So having a tool that tells you when there are no more cancer cells left is kind of our holy grail.”

Their MRD test, called Foresight CLARITY, launches first for lymphoma next year, with solid tumor applications in development. As their data have already begun to reshape the standard of care, Jake and Dave discuss a future in which MRD testing could come before PET scans—or even replace them.

“We want MRD testing to become the standard of care across all cancers treated with curative intent,” says Jake. With Foresight CLARITY already in three prospective trials and in NCCN guidelines, and a clear clinical need, that vision may not be far off.

In this episode of Mendelspod, we explore Illumina’s new 5-base solution with Dr. Bodour Salhia, a cancer epigenetics researcher at USC’s Keck School of Medicine, and Danielle Goldberg, senior product manager at Illumina. The conversation brings together the researcher’s perspective and the technology developer’s vision on how this advance could reshape cancer research.

Dr. Salhia explains why DNA methylation is such a powerful lens into cancer biology:

“DNA methylation is fundamental for regulating gene expression and maintaining genome integrity. It’s also one of the earliest tumorigenic events that often precedes genetic mutation.”

She details the challenges of older methods like whole-genome bisulfite sequencing and why her lab was eager to test the new workflow.

Goldberg describes what makes Illumina’s 5-base solution a leap forward:

“It’s a single assay that gives you dual insights—one library prep, one sequencing run, and an analysis pipeline that enables the detection of both genomic variants and methylation with high accuracy.”

Together, they discuss how combining genetic and epigenetic information in one streamlined workflow not only increases efficiency and reduces cost but also eliminates biases introduced by multiple assays. The result, they say, is a more integrated view of cancer biology and more accessible research at a time when budgets are tightening.

Looking ahead, both Salhia and Goldberg envision deeper integration of genomic and epigenomic data accelerating discovery and biomarker development.

To learn more about Illumina’s 5-base solution, tune into an upcoming webinar here.

Turns out, not at all.

Patel — a veteran of PacBio, 10x Genomics, and founder of 2D Genomics — is back with a bold rethink of thermocycling itself. His new platform, IconPCR, isn’t just another black box with 96 wells. It’s the first of its kind to feature independently controlled wells, enabling real-time amplification, quantification, and normalization — all in a single run. If PCR was once just about making more DNA, IconPCR is about making just the right amount, at just the right time — and eliminating the variability that can quietly wreck your sequencing before it even starts.

“Instead of me telling it how many cycles, I can tell it how much DNA I want — and it will determine the cycles by itself. That’s the fundamental shift,” he says.

But maybe the bigger shift is cultural — a refusal to treat sample prep as solved, and a willingness to build new tools for today’s applications, not yesterday’s.

“It gets branded as a PCR machine. But honestly, the capability of it is so much more. It does what would otherwise take multiple instruments — and it does it from day one.”

With a blend of unaffected humor and technical rigor, Pranav walks us through the frustration that led to this innovation, the simplicity of the idea, and the engineering feat that makes it possible.

Funded through Florida’s landmark Sunshine Act, the new institute is part of a broader vision to create a statewide pediatric genetics network and pilot universal newborn whole genome screening. Ledbetter walks us through how this model could reshape not only early diagnosis but the entire standard of care for children with rare genetic conditions.

* 0:00 From 5 to 50% rare disease diagnosis

* 4:00 The MyCode story at Geisinger

* 7:00 Leading the new pediatric rare disease institute at FSA

* 11:20 Moving closer to universal newborn screening

* 20:20 More information is better

* 34:00 WGS as universal platform

Ledbetter is bullish on whole genome sequencing (WGS) as the foundation for future genetic testing:

“Whole genome sequencing is becoming the universal platform for genetic testing. That greatly simplifies testing—physicians no longer need to know dozens of platforms. They just need to provide good clinical info, and we’ll handle the rest.”

He also makes the ethical case for early diagnosis as a matter of patient rights:

“If you really have a genetic technology that can identify every rare genetic disease individual at birth, that child has the right to be found.”

From the cost and logistics of trio testing to the promise of AI in variant interpretation, this conversation offers a powerful glimpse into where rare disease diagnosis is headed—and why Florida may be leading the way.

Joining the conversation are three scientists who worked closely with him and continue to carry forward his vision:

* Dr. Marina Sirota, UCSF professor and acting director of the Bakar Computational Health Sciences Institute,

* Dr. Chirag Patel, associate professor at Harvard’s Department of Biomedical Informatics,

* Dr. Mike Snyder, chair of genetics at Stanford and longtime collaborator.

Together, they reflect on Atul’s energy, his fearlessness, and his talent for getting to the right question. “Nearly everything I know about doing science I learned from Atul,” says Marina. “He taught us how to ask the right questions—and how to tell the story so others would care.”

Chirag speaks to the connective tissue of Atul’s thinking: “He helped us link previously disconnected fields—gene expression, hospital systems, exposures—and showed us that the real frontier is in the integration.”

Mike recalls Atul’s blunt honesty and unmatched creative force: “He was a fire hydrant of ideas. When others were cautious, he just said it like it was. And often, he was right.”

The episode traces Atul’s influence from his early work mining public gene expression data at Stanford, to building the UCSF clinical data warehouse and leading data-sharing efforts across the entire University of California system. In each role, he remained committed to one core belief: that data should not sit idle—it should lead to insights, tools, and ultimately, better health for patients.

From early exposomics to the new AI-enhanced diagnostics, his legacy stretches across the most urgent frontiers in biomedical research today. As Mike puts it, “There were no boundaries in Atul’s science. He just moved—quickly—into what mattered.”

Most cancer biomarkers aren’t found in your DNA—they’re found on a microscope slide. And according to Dr. Andy Beck, CEO and co-founder of PathAI, that slide is undergoing a digital transformation.

In this episode, Andy takes us behind the scenes of modern pathology to reveal how AI is reshaping not only cancer diagnostics but also drug development. From…

* 0:00 How has AI changed regulatory informatics?

* 4:15 KISS

* 12:50 On standards

* 25:00 So nothing new about AI? The juicy question of the interview

* 32:45 Raju’s life: good days and bad nights

Despite the buzz around AI, Raju insists the fundamentals haven’t changed much. “It still essentially follows the same patterns,” he says. “Here's data that needs to be analyzed in order to help make a safety and efficacy decision.” What has changed is scale: more data, more submissions, more complexity. But also more tools.

On that note, Raju makes a strong case for keeping it simple. “It's a really strange choice to do something like a complex language model when all you really need is a string search,” he says. Simpler tools not only reduce costs and computing overhead, they’re more transparent—an essential trait in a regulatory environment where explainability is everything.

Oh, come on, Raju . . . what’s really different about AI? He warns against blind trust in black-box models, especially when trained on biased datasets.

We also explore cloud adoption, standardization, and the global regulatory landscape. Raju explains how DNAnexus is working behind the scenes with agencies around the world to implement trusted environments and validate evolving standards.

“Genomics works. Don’t be scared of it.” That’s the message from Mike Kreitzinger, a longtime Illumina leader now advising the Institute for Pediatric Rare Disease at Florida State University and stepping into a broader role as a genomics advocate.

In this episode, Mike gives us an inside look at Florida’s newly funded Sunshine Genetics Act, which includ…

“We’ve moved from offering modular tools to building full-stack solutions,” Jing explains. “Connected Insights is about taking raw genomic data and delivering meaningful answers—quickly and consistently.”

* 0:00 With Connected Insights, Illumina now has end-to-end support

* 4:30 What’s your niche in oncology?

* 10:40 Can software really interpret biology?

* 14:45 What’s new and updated?

* 17:00 The future of genomic interpretation in oncology

From variant annotation to case summaries aligned with clinical guidelines, Connected Insights integrates more than 55 curated databases, AI-driven tools like SpliceAI and PrimateAI-3D, and a design philosophy that emphasizes both comprehensiveness and human-centered transparency.

Gao previews upcoming innovations—such as integration with Illumina’s MRD and Constellation technologies—and paints a future where interpretation is more automated, collaborative, and expansive.

“Our goal,” says Gao, “is not to replace scientists, but to scale their expertise. Connected Insights is an intelligent assistant that amplifies what experts do best.”

🎧 Also, don’t miss the GenomeWeb Webinar on July 9 at 10 AM EDT, where Jing Gao and team go deeper into real-world use cases and the future of variant interpretation in precision oncology.

Can we finally replace animal testing in drug development—and still know a drug is safe and effective?

That’s the provocative question at the heart of this episode, as we sit down with Andrei Georgescu, co-founder and CEO of Vivodyne. The company is developing robotic, AI-enabled systems for growing living, biopsy-like human tissues that can be used to t…

With her background in hematopathology and molecular diagnostics, Rita brings clarity to a field that has long promised transformation—and is now delivering. “It’s not the future anymore. It’s actually here,” she says. Liquid biopsy has moved beyond the buzzword phase and is increasingly integrated into both clinical trials and standard care for cancers like non-small cell lung cancer.

We talk about why fluids are such a powerful source for diagnostics, with Rita reminding us, “Sixty percent of our body is water.” Sampling these accessible fluids not only makes for less invasive testing but also captures the heterogeneity and clonal evolution of diseases like cancer better than traditional biopsies.

Rita also offers a tour through the latest technology advances, from target enrichment chemistry to the rise of multiomic platforms, including Agilent’s Avida portfolio. “There are 30 million CpG sites in the genome that can be methylated,” she explains, highlighting why DNA methylation is such a rich source of diagnostic information.

She discusses the operational hurdles labs face in adopting liquid biopsy—chief among them being assay complexity and staffing—and how automation and customizable panels are easing the way.

The show concludes with a call to action: "We are very slow often as a medical community adopting new tools. I hope we will democratize access as the clinical evidence grows.”

Bonus: To go deeper, listeners are invited to attend a GenomeWeb webinar on July 8th, presented by Dr. Nicola Normanno, a leading voice in the liquid biopsy space.

What’s at stake? In Europe, labeling GMOs is not just a policy—it’s the law. Debode emphasizes that public trust hinges on scientific transparency: “Thanks to correct labeling, people can choose if they decide to eat or not food that is coming from GMOs.”

* 0:00 What led you to GMO detection?

* 4:00 How has your approach evolved?

* 11:00 NGS plus target enrichment

* 16:10 What are you testing?

* 21:00 The future of GMO detection

The conversation dives into the challenges posed by CRISPR and other new genomic techniques (NGTs), which can make single-base edits indistinguishable from natural mutations. “With CRISPR,” Debode explains, “you are not obliged to introduce a large fragment into the genome. You can just modify one base… and in fact, you will have a big effect.”

Debode outlines how CRA-W is adapting its toolkit to these challenges, turning to high-throughput sequencing with target enrichment technology to screen for even subtle genetic changes. He also shares how Belgium and the EU are investing in collaborative efforts like the DETECTIVE project to establish viable detection protocols across a broad diversity of organisms.

The work isn’t just regulatory. CRA-W is partnering with farmers and industry to improve diagnostics, ensure safety in bio-based fungicides, and support sustainability through gene mapping. “We’re not doing this alone,” says Debode. “There’s a strong European network working together to make these tools applicable and enforceable in the field.”

For more from Debode on GMO detection, tune into an upcoming GenomeWeb Webinar here.

In this compelling reunion with spatial biology pioneer Joe Beechem and a first-time visit from Oliver Braubach, we explore the rapid evolution of spatial technologies at Bruker, a legacy instrumentation company newly resurgent in the spatial space. Following Bruker’s acquisition of Nanostring and Canopy, the company has emerged as a unifying platform where whole-transcriptome discovery meets translational assay development—under one roof.

* 0:00 Red alert: we don’t yet understand how tissue biology works, and don’t let anyone tell you we do.

* 5:12 Customer of spatial turned toolmaker

* 10:00 What do you want researchers to know about Bruker Spatial?

* 14:24 How do you go from discovery to assay?

* 18:09 How has AI impacted spatial?

* 22:41 The ongoing question of reductionism

* 31:00 What’s your biggest challenge?

Beechem, known for launching the first high-plex spatial platform at Nanostring, returns to Mendelspod to declare that spatial biology may be more consequential than genomics itself. “If somebody tells you they understand how tissue biology works, you can just cut them off. They don’t,” he says, describing the dramatic leaps from 84-plex in 2019 to 20,000-plex subcellular imaging today.

Braubach, a neuroscientist turned toolmaker, shares his journey from early customer to R&D leader, developing user-friendly platforms that empower researchers with flexibility and speed. “We want researchers to assume again a degree of power over their assays,” he says, outlining Bruker Spatial’s mission to integrate discovery and translation.

Together, the two leaders discuss how AI is accelerating the power of spatial, with foundational models that can identify patterns humans can’t. Beechem recounts feeding high-plex images into a GPT model: “It came back and told me where to look. And it was right.”

They also reflect on the philosophical shift spatial enables—moving beyond genomics' reductionist lens toward a more holistic view of biology in situ. “The hype around spatial is not hype,” says Beechem. “It’s real.”

In this episode of Mendelspod, Theral sits down with Rob Neely, co-founder and CSO at Tagomics, to discuss how his company is fusing genomics, epigenomics, and fragmentomics into a single, assumption-free assay for early cancer detection. The conversation begins with breaking news: Tagomics has just received a new grant from the UK’s Innovation Agency a…

In this premium episode of Mendelspod, we’re joined by one of the few people speaking clearly and globally about biosecurity in the era of synthetic biology and AI: Sophie Peresson.

A consultant and leader in responsible innovation, Sophie brings an unusually broad and grounded perspective. With experience spanning international law and governance, she p…

As artificial intelligence continues to influence the life sciences, some researchers are questioning not just what it can predict, but what it can explain. On this episode, Mike Kiebish, VP of Platform and Translational Sciences at BPGbio, discusses the company’s “biology-first” approach to drug discovery—one that begins not with models or literature, …

Knott introduces the listener to RNA not just as code, but as living language. He discusses how AI now allows scientists to see molecules in 3D at the beginning of a project rather than years into it: “You can take that protein sequence, run it through something like AlphaFold, and there it is, looking at you.”

* 0:00 RNA - the shapeshifting paradox of a molecule

* 4:05 Using AI: here’s an idea—maybe we know enough about biology

* 6:50 The ARC Institute, and that one paper

* 9:05 Structural biology at everyone’s fingertips

* 18:10 Why are gene therapy companies going so slow?

* 23:40 The grammar of RNA

With infectious curiosity, Knott explains how protein design is entering an era of intent, not just discovery. “Maybe we understand enough about the rules of biology,” he posits, “that we can design the proteins we need.” He describes his lab’s twin tracks: mining microbial genomes for novel RNA-guided machines and using generative AI tools like RosettaFold and BindSpace to build bespoke editors of DNA and RNA.

The conversation touches on emerging efforts to mitigate off-target effects in gene editing using AI, the data limitations holding back RNA-protein modeling, and a powerful metaphor comparing static protein images to photos of horses.

Knott makes a striking point: “We’ve known the spelling of RNA for a while, but now we’re trying to learn its grammar.” This, he explains, means understanding not just RNA’s sequence but its shape, movement, and silent punctuation marks—an effort he sees as the next frontier.

For decades, drug discovery has followed two main roads: small molecules that can slip into cells but often lack precision, and biologics that offer specificity but struggle with delivery and manufacturing. In this episode, Christian Schafmeister introduces us to a third path: spiroligomers—synthetic, fused-ring molecules designed to combine the best of…

In this episode of Mendelspod, Theral sits down with Aridni Shah, co-founder and CEO of Immunito AI, a Bengaluru-based biotech startup reinventing how we develop antibody therapies. Shah and her team are using artificial intelligence to design antibodies from scratch, bypassing traditional animal-based and data-heavy methods. “We no longer need to rely on pre-existing data,” she explains. “We’ve gone to the fundamental atomic level and learned basic physics, chemistry, and maths—why do two proteins interact?”

* 0:00 Discovering new antibodies without relying on biological processes

* 4:45 The platform - a structure first approach

* 10:00 The business model

* 15:05 Bringing mathematics and physics to biology

At the heart of Immunito’s innovation is a proprietary mathematical transformation that translates raw 3D structural data into rich, generative models capable of designing antibodies for even “undruggable” targets. It’s an ambitious approach to rational drug design that prioritizes data efficiency, leveraging physics-based complementarity rather than brute-force sequence matching.

Still early in development, Immunito is already seeing promising lab results and aims to partner with pharma while building its own pipeline. “We should have signed a few multimillion-dollar multi-target deals,” Shah says of their goals over the next few years, “and be looking to progress towards IND.” This conversation opens a compelling window into how AI, when grounded in mathematical and physical intuition, may radically transform biology.

Yes, the Trump economy has been tough on life science tools—but according to today’s guest, the business model was failing us anyway. It’s time to go back to rethinking the basics.

Today we’re joined by Stephane Budel, founding partner at DeciBio, one of the leading market research and consulting firms focused on life science tools and precision medicine…

On today’s episode of Mendelspod, Theral sits down with Giovanna Prout, CEO of Scale Biosciences, to explore a how the company is achieving new orders of magnitude of scale in the single cell space.

"In the past, single cell was one cell per well—maybe 96 cells per experiment," Prout explains. "Now, with our Quantum Scale platform, we can scale from 85,…

* 0:00 The ultimate science app

* 2:15 A use case

* 7:15 How does VR interaction change things?

* 12:47 Intuition at the nanoscale

* 23:10 Can VR redefine biological models and become the norm?

* 35:15 Hard to give career advice now with rapid rise of tech

Nanome’s VR platform enables researchers to grab, rotate, and manipulate proteins, explore molecular dynamics, and even collaborate remotely inside a shared molecular environment. Built with both scientific rigor and the playful spirit of a 3D gamer, Nanome is already being used from classrooms to major pharmaceutical firms.

One of the most compelling ideas discussed today is the possibility that VR can help biologists build intuition at the nanoscale, much like space exploration and science fiction helped earlier generations develop intuition about the cosmos. "Ninety-nine percent of people have no intuition for the nanoscale," McCloskey says. "You look at molecules on a 2D screen, and it's like a ball of spaghetti. But in VR, you pretty much instantaneously get it."​

This new kind of "nano-intuition" could, McCloskey argues, open doors for faster discovery, better communication, and broader scientific literacy. As he puts it, "Space is fascinating because it's so vast and mysterious. But the nanoscale is even denser with phenomena—and we’re just beginning to explore it."​

Looking ahead, Steve sees VR as becoming a normal part of the scientific workflow. Though today's headsets are still bulky, future versions could be as light as eyeglasses, embedding a whole new layer of spatial computing into everyday research.

As Steve says: "If we can give scientists—and even the general public—intuition for the nanoscale, it might radically change how we approach biology, drug development, and science education itself."​

Wait! What? Sequencing as a service?

That was the reaction when Mark Budde first set out to upend a basic ritual in molecular biology—confirmation Sanger sequencing—with his company Plasmidsaurus. You’ve heard it many times: Illumina machines sequence around 80% of the bases in the world. But as Mark points out in today’s interview, it’s not 80% of th…

Today we talk with Sarah Overton, Senior Director of Revenue Cycle Management at Velsera, whose team helps clinical labs with everything from validation to reimbursement strategy. She walks us through the practical implications of the ruling. “It came just in time. Even meeting stage one was going to be incredibly burdensome,” she says in today’s interview. (Link to a webinar with Sarah on this topic here.)

* 0:00 Impact of recent court decision on LDTs

* 5:15 Supports an in-between regulation

* 15:15 How are your clients choosing between LDT and IVD?

* 20:00 Topic goes hand-in-hand with reimbursement

* 25:20 Every test is different

Instead of scrapping oversight altogether, Overton argues for a middle ground — more robust than the current CLIA framework, but less rigid than the FDA’s approach. “We need something in between,” she says. “There are already mechanisms in place — like MolDX’s technical assessment — that address analytic validity, clinical validity, and clinical utility. That could be a model to build on.”

We explore how Velsera’s clients are choosing between launching LDTs or IVDs, and what factors drive that decision. Overton emphasizes that reimbursement strategy must be integrated from the beginning — not bolted on at the end. “The test might be clinically excellent, but if it’s not reimbursable, it won’t sustain a lab,” she warns.

“We need standards that ensure quality without crushing innovation,” she says. “There are ways to do that now. Let’s build on what’s working.”

Calling this the "tinkering phase" of AI, Chris likens the current moment to the early days of the web—when best practices were still forming and every developer had to invent their own solutions. “It’s one of the most exciting times to be a software developer,” he says, describing how AI has enabled a leap forward in productivity across the board—from writing code to streamlining negotiations and customer service. One internal tool, Elisa, functions like a fine-tuned ChatGPT within Slack, answering employee and customer queries on the fly.

AI, he says, is speeding up nearly every part of the business. "There are all of these problems that were impossible to solve a year and a half ago. And now you can solve them. One of the hardest things… is your old preconceptions of what you're capable of? You have to let some of that go because you're capable of so much more now."

Petersen also talks risk: while AI promises a democratizing effect, making outsourcing more accessible to small players, he warns of the dangers of consolidation—where just a few massive models hold everyone’s data. To avoid that future, Scientist.com is building its own internal LLMs, training and fine-tuning models like Mistral and DeepSeek on proprietary data, all under an evolving platform they call Benchmate.

Scientist is betting that AI will not only enhance their marketplace but change how science itself is organized and conducted. Stay tuned for more in this new series on AI.

Klco and his team have identified twelve novel molecular subtypes of pediatric AML—some driven by genetic alterations that had long gone undetected by standard computational tools. Chief among these is the UBTF tandem duplication, a complex mutation previously overlooked but now shown to be a distinct disease subtype that accounts for up to 10% of pediatric AML cases and is associated with relapse and poor outcomes.

“We’ve been misclassifying childhood AML for years,” says Klco. “It’s the same disease as in adults—but it behaves very differently. And we’ve been using an adult framework to treat kids.”

* 0:00 We’ve been misclassifying childhood AML

* 7:25 Challenges with current treatment paradigm

* 11:05 Doing clinical whole genome and RNA sequencing

* 17:25 How might this new approach work for other pediatric cancers?

The conversation delves into how St. Jude’s use of whole genome and RNA sequencing, paired with advanced analytics, has enabled more precise subtyping. In response, Klco’s team is already developing targeted therapies, including the use of menin inhibitors, which have shown early promise.

But discovery is just one side of the coin. Implementation is another. Klco discusses the development of a new 357-gene panel—specifically designed for pediatric cancers and incorporating structural variants—that is now in clinical use at St. Jude. It fills key gaps in diagnosis, risk stratification, and minimal residual disease monitoring, especially in complex cases such as post-transplant patients or those whose tissue samples are incompatible with full genome sequencing.

Asked about future potential, Klco notes that while most pediatric cancers may now be genomically defined, new methods such as long-read sequencing and methylation profiling still hold promise for sharpening diagnostic tools and stratifying risk.

“Pediatric cancers are driven by different genomic forces than adult cancers,” he explains. “Even within the first 18 years of life, we see distinct subtypes emerge at different ages. If a child under three comes in with AML, I already have a good idea what subtype it might be.”

It’s a compelling example of how detailed genomic subtyping is not only advancing our understanding of pediatric disease—but directly shaping the next generation of therapies.

Dr. Viny’s research focuses on the epigenetic architecture of hematologic malignancies, exploring how errors in chromatin structure—not just mutations in DNA—can lead to cancer. “Cancer, at its root, is often a disease of dysregulated identity,” he says. “Cells that have lost their ability to regulate their own gene expression are primed for malignant transformation.” This breakdown in regulation becomes a doorway to cancer—a perspective that reshapes how we think about both origin and treatment.

* Chapters:

* 0:00 Leukemia free for 21 years

* 5:25 Life as a researcher at Columbia University today

* 8:30 Epigenetics and cancer etiology

* 17:03 Impact of new spatial and single cell tech

* 25:00 What is hypomethylating treatment?

* 28:40 Using type and proximity of cell surface proteins to understand immune regulation

* 34:15 What next?

Dr. Viny discusses how emerging spatial and single-cell technologies are giving researchers a new kind of lens into these processes. The tools allow him and others to study not just what genes are expressed, but where in the tissue and in what context—something that’s proving crucial for understanding the complexity of the tumor microenvironment. He highlights the use of Pixelgen's platform for analyzing cell surface proteins, which offers fine-grained insights into how immune cells interact with cancer cells. “The type and proximity of cell surface proteins,” he notes, “tell us an entirely new story about immune regulation.”

He also speaks candidly about the realities of doing science today, especially within a strained academic system. Despite recent threats to research funding at Columbia, Dr. Viny remains resolute: “If we’re not investing in understanding cancer, what are we doing?”

"We’re no longer in a world where we’re doing genomics or imaging or proteomics," he explains. "These things are all coming together, and it’s important that they do. The UK Biobank will soon have 80 million images."

Busby highlights the UK Biobank’s leading role in this transformation, with its extensive genomic, imaging, and clinical data available to researchers worldwide. He emphasizes the importance of enabling scientists to access and analyze vast datasets collaboratively while ensuring participant privacy, and points to the role of DNAnexus in providing a trusted research environment where multiple stakeholders, from pharma to academia, can work with data efficiently and securely.

The episode also explores the impact of AI in bioinformatics, particularly in hypothesis generation. "AI is helping us think beyond single-cause events," Busby notes, referencing its ability to generate novel insights from complex biological data. He underscores the need for proper alignment between AI systems and scientific goals, stressing that human intuition remains essential in guiding these technologies toward meaningful discoveries.

As the field moves forward, Busby calls for more equitable data sharing practices, ensuring credit for data generators and benefits for study participants. "We need to figure out how to incentivize data generation in a way that’s fair and equitable," he says.

While synthetic biology is full of exciting opportunities in this new age of AI, the field is not without its macro-economic challenges. The current political climate has many wondering if we have failed in our science communication. Cumbers says synthetic biology has yet to experience its "ChatGPT moment" — a breakthrough that not only advances the science but brings it into public awareness, making it as familiar and accessible as AI has suddenly become. When will biology become democratized, when will more people participate directly in shaping it, or even just understand it? That question lingers at the heart of this year’s meeting.

We also discuss themes from the conference program, including the focus on longevity, organ replacement, non-canonical amino acids, and the tight coupling between biology and computation emerging across the field.

As always, John brings insight into a field that, for all its progress, still feels like the early days — we’re just seeing the first bands on the gel.

* Mendelspod listeners receive 10% off SynBioBeta registration. Use the code Mendelspod when registering.

Chris Mason shares new insights from his work on the Space Omics and Medical Atlas (SOMA), the largest collection of astronaut health data to date. His latest findings confirm that space is more than a hostile environment—it’s a revealing one. Space is a kind of alternate reality that lets us test fundamental questions about biology and human health. Mason says changes in telomere length, immune system behavior, and skin inflammation during spaceflight are offering a new window into how the body responds to stress—whether in orbit or in disease states like cancer on Earth.

Enter Pixelgen’s breakthrough technology, the proximity network assay, which allows researchers to map how proteins are organized on the surface of immune cells with nanoscale precision. As Fredriksson explains, “Cells don't operate only by parts lists, but by how they're organized to do all their functions.” Their approach enables the first large-scale spatial mapping of protein-protein interactions in three dimensions using DNA sequencing—unlocking insights not possible through traditional single-cell or bulk assays.

In a collaborative effort, Mason’s lab and Pixelgen are applying this technology to study T-cell dynamics during spaceflight and in acute myeloid leukemia (AML). The results are striking: specific protein markers cluster together only during spaceflight and only at relapse in leukemia, offering clean, quantifiable signatures with clinical potential.

As Mason puts it, “This is a new modality of data—it forces you to ask, ‘Well, what does this mean?’ And you’re like, ‘Well, we’ve never seen it before.’ So we’re figuring it out.” Whether predicting relapse in cancer or designing better drugs for space and Earth, cell surface proteomics is opening a new frontier in biomedical science.

2024 marks a “watershed year” for PacBio, with the launch of the Vega system—a benchtop long-read sequencer at an unprecedented $169,000 price point—alongside major advancements in automation, bioinformatics, and sample prep. According to Henry, this is the first time in PacBio’s history that they have “the full product,” allowing researchers to access long-read sequencing more easily than ever before. The response has been overwhelming, with demand outpacing supply and 70% of Vega inquiries coming from new customers.

But the conversation wasn’t just about technology. Henry voiced deep concerns over the current political and funding landscape, particularly regarding NIH uncertainty. He strongly defended the past 50 years of biological progress, warning: “It would be a shame to undo that.” Despite economic pressures, he remains optimistic about the future of genomics, noting how long reads are not only competing with short reads on cost but unlocking new areas of discovery—from the dark regions of the genome to phased haplotypes and epigenetics.

Henry is always a great discussion partner. Join in this interview about the evolving sequencing market, PacBio’s competitive strategy, and what’s at stake for the future of genomics.

It’s time for our annual deep dive into sequencing—no, wait—multi-omics! Back on the show is our resident sequencing guru, Keith Robison, scientist at Ginkgo Bioworks and author of the OmicsOmics blog. Keith is our all time return champion, and as always, he brings technical experience alongside the storytelling instincts of a seasoned journalist.

Keith …

Originally from Lebanon, Ghemrawi’s path to forensic science began in the medical field before she earned a Fulbright scholarship to study in the U.S. and ultimately pursued a PhD in forensic genetics. “I always knew I had a passion for forensics,” she says. “There weren’t many opportunities back home, but I knew that any science-related field would help me get there.”

One of the most exciting areas of her current research involves using genetic and epigenetic markers to predict what a suspect may look like—an approach that, when combined with forensic genetic genealogy, could revolutionize investigations. “The idea is that we can not only get human identification from DNA but also predict age, eye color, hair color, and even certain phenotypic traits,” she explains. “If this works, it could help narrow down family trees in genealogical investigations.”

The conversation also touched on the evolving challenges in forensic science, particularly as DNA analysis becomes more sensitive. Questions around DNA transfer—whether genetic material was directly or indirectly placed at a crime scene—are increasingly shaping legal arguments. “We can now get a profile from an incredibly small sample,” Ghemrawi notes, “but that raises questions about how the DNA got there, and courts are having to consider these new complexities.”

Ghemrawi is passionate about mentoring the next generation, particularly encouraging young women to step into forensic science. “The only way you know you can’t do something is by trying,” she advises. “Ask questions, be persistent, and don’t be afraid to push into new territory.”

“Research is like fishing,” Greely explains. “You cast your net, and sometimes you catch something big, sometimes you don’t. But if you stop casting altogether, you’re guaranteed to catch nothing.” He argues that long-term investment in science is the only way to sustain real progress, even if individual studies don’t always yield immediate breakthroughs.

Greely also draws a stark historical comparison, warning that the current climate resembles the Communist Cultural Revolution, “except this time the war on expertise and knowledge isn’t coming just from the top down—it’s being fed from every direction.” The consequences, he suggests, could be felt for generations.

Yet, while calling for outspokenness, Greely also urges compassion for those in academia and government who feel they cannot safely speak out. “Some of the people who aren’t being as forthright as we’d like—it’s not personal cowardice,” he says. “They’re trying to protect their institutions, their labs, their students, their colleagues. And that’s something we need to understand, even as we push for change.”

At the heart of Aikium’s approach is Yotta-ML2, an AI-powered wet lab platform that searches the vast combinatorial space of proteins to create precise, bespoke binders for disease targets that have long been out of reach. “The combinatorial space for how many proteins can bind a region is very large,” Iyer explains. “Experiments are limited to 10⁹ to 10¹² possibilities, but the theoretical space exceeds 10¹⁵. We’re using AI to intelligently navigate this massive search problem and find what actually works in the body.”

Iyer is clear-eyed about the biggest challenges ahead: “AI is just hype if it can’t deliver better therapies, faster,” he says. “The biggest barrier isn’t just designing binders—it’s making sure they work in human biology, avoiding immunogenicity, and accelerating the slow feedback cycle of drug development.”

Looking to the future, Iyer envisions a major shift in the industry: “We’re living in an age of exponential technologies. Just as AI has transformed other fields, it’s going to compress the timeline and risk of therapeutic development. In five or six years, we’ll see a wave of AI-designed molecules entering the clinic.”

"What you're cutting is cancer funding. What you're cutting is Alzheimer's research. What you're cutting is funding for sick kids," Hercher warns, pushing back against the rhetoric that frames these cuts as mere "overhead reductions."

She breaks down how diversity strengthens both scientific databases and the research workforce, emphasizing that genetic studies are incomplete without diverse representation. She also addresses the political motivations behind these attacks, highlighting the broader pattern of anti-intellectualism and anti-science sentiment creeping into public policy.

Hercher closes with a powerful statement about her own institution’s commitment to DEI:"We are not changing a damn thing. We think it's right, and we're sticking to it."

Join us today and make your own voice heard if you’re concerned about the future of scientific research and equity in medicine.

Editor’s Note: Today’s show is dedicated to our late Executive Producer, Ayanna Monteverdi.

Lung cancer is the most deadly of all the cancers worldwide. Very few of those who should be— are getting screened. There is enormous medical need here, and early cancer detection through advanced liquid biopsy could be a tremendous part of the answer.

Today, as part of our series on the future of genetic testing, we welcome Susan Tousi, CEO of Delfi Diagnostics, a company pioneering next-generation liquid biopsy technology for early cancer detection. Tousi came to the post a year ago formerly serving as Illumina’s Chief Commercial Officer. Delfi has made significant strides in developing affordable, high-sensitivity blood-based tests focusing on lung cancer.

Tousi discusses the company’s groundbreaking approach, which leverages whole-genome sequencing and machine learning to detect cancer at its earliest stages.

"We believe that for early detection to make a difference and make cancer less deadly, you have to be catching it at stage one or stage two," she emphasizes.

By using a low-pass sequencing method, Delfi is able to keep costs low while maximizing sensitivity, making widespread screening more accessible. The conversation highlights the dire need for better lung cancer screening methods, given that fewer than 6% of eligible individuals undergo annual screening with low-dose CT scans.

"Lung cancer alone takes more lives annually than colorectal, breast, and cervical cancer combined," Tousi notes.

Delfi aims to change this with its simple blood test, already in commercial use and being adopted by major healthcare systems such as OSF HealthCare and Allegheny Health Network.

Beyond lung cancer, Tousi also shares insights into Delfi’s broader vision, including its work on liver and ovarian cancer detection, as well as its potential in tumor monitoring.

"Every day that goes by without better screening means lives lost that we could have saved,” she states.

In our first conversation with Deep Genomics, Theral sits down with Brendan Frey, the company's founder and Chief Innovation Officer, to explore the power of AI in RNA biology and drug discovery. Frey, a pioneer in deep learning who trained in the lab of AI luminary Geoffrey Hinton, shares how his personal experience in genetics back in 2002 led him to merge machine learning with genomic medicine. The company has a head start.

In the past year, Deep Genomics has built Big RNA, the first foundational model for RNA biology, trained on over a trillion genomic signals.

"RNA is the ideal point of intervention," says Frey. "It’s the software of biology—it takes context into account, shaping how DNA functions across different cells and conditions."

Busby reflects on his journey into the field, which was influenced by key projects and experiences during his time at the NCBI and his genomics hackathons. He outlines the current genome informatics landscape, emphasizing DNAnexus' role in fostering collaboration. Busby highlights transformative movements to refine disease subtyping based on haplotype data, underscoring their potential to reshape diagnostics and research.

As for the use of the new generative AI in bioinformatics, Busby says, "It is not super good at making data into information. And it’s not particularly good at making information into knowledge, but it does understand something about making knowledge into impact.”

Looking ahead, he envisions a future where genome informatics drives precision medicine and fosters global collaborations leveraging more diverse genomic data. He ends with a call for longitudinally resolved databases.

As 2025 begins, we are launching a new series The New Genetic Testing. To do that we’re welcoming today Dr. Ezra Cohen, Chief Medical Officer at Tempus to offer a behind-the-scenes look at how the company is transforming healthcare through cutting-edge AI. With its recent successful IPO, Tempus has firmly established itself as a leader in genomic testing and multimodal data integration and empowering providers and life sciences companies to make better decisions for patients.

"Tempus is really a tech company applying sophisticated AI to the healthcare space," explains Dr. Cohen. With tools like TempusOne, an AI-powered assistant, oncologists and other clinicians can access real-time insights, from interpreting genetic tests to exploring treatment options and clinical trials.”

Dr. Cohen highlights Tempus’ unique approach to data collection, amassing 300 petabytes of multimodal data—50 times larger than the largest public oncology database. This vast resource, paired with advanced AI, allows Tempus to provide unparalleled context for each patient.

"We’re not just saying this cancer has this gene mutated. We’re layering genetic mutations, co-mutations, expression levels, radiographs, digital pathology, and treatment outcomes to give providers a comprehensive picture," he says.

As Tempus continues to expand its offerings and impact, Dr. Cohen envisions a future where AI reshapes every aspect of healthcare, from patient interactions to drug development.

"The future is disruptive, and it's going to change incredibly fast. Fasten your seatbelts—we’re in an amazing time."

This week we welcome the innovative minds behind PredixBio, a new and groundbreaking company at the forefront of spatial biology. CEO Dusty Majumdar and co-founder Chakra Chennubhotla join us to discuss their mission to revolutionize cancer therapeutics through spatially intelligent biology. Founded in 2018 and supported by NIH grants, PredixBio focuses on unraveling the tumor microenvironment's heterogeneity using cutting-edge analytics and explainable AI. Their SpaceIQ platform integrates images and transcriptomics to predict patient responses to immunotherapy with an accuracy of over 90%.

Chakra studied under AI pioneer Geoffrey Hinton, often referred to as the "godfather" of AI. He explains the transformative potential of spatial analytics.

"Heterogeneity is not random; there is an order to it. Understanding this order allows us to uncover mechanisms hidden in the data."

Dusty highlights the company's mission, emphasizing the importance of explainability in AI for clinical trials and drug discovery.

"We don’t just provide predictions; we explain why patients respond—or don’t—to therapies. This helps redefine new targets and improves outcomes."

Join in to find out how PredxBio's new approach is setting new standards and shaping the future of spatial biology and precision medicine.

"We lack a way of training genomic AI as readily as you would for natural language processing,” says Farh. "There are vast amounts of data, but there are no labels, no supervision. One of the most powerful tools that we’ve found is using clues from natural selection.”

Farh says the company began the AI lab seven years ago when deep learning took off. Two of the team’s AI algorithms, PrimateAI-3D and SpliceAI, published in Cell and Nature Genetics, were among the first examples of deep learning algorithms in genomics to become widely used by clinical labs and researchers in interpreting variants of unknown significance.

What will be the long-term impact of AI on genomics?

Chapters:

0:00 First-of-kind studies to utilize AI to decode variation in humans

3:00 Training genomic AI on natural selection

9:10 What sets Illumina’s algorithms apart?

11:40 Insights of PrimateAI-3D and SpliceAI

21:40 How will AI impact genomics long term?

In this episode of Mendelspod, Theral sits down with Dr. Mohamad Takwa, co-founder and CEO of Epigenica, a Swedish startup revolutionizing epigenetic research. Epigenica is positioning itself at the forefront of this new and rapidly growing field with a mission to empower researchers through large-scale epigenetic profiling.

In this episode, Dr. Lewis joins Theral in our ongoing series on minimal residual disease (MRD) testing, a revolutionary blood test that is helping detect residual cancer causing a paradigm shift in patient management.

Dr. Lewis belongs to a pioneering group that allows oncologists to specialize in a single cancer type. He says MRD testing has transformed his own practice, describing how this “liquid biopsy” approach, previously common in hematology, is also advancing the detection of solid tumors.

“News flash,” he says in today’s show. “We were trained a certain way.  My training ended 12 years ago, and I had fantastic training.  I did my fellowship at the Mayo Clinic.  But if I practiced now the way I was trained then, my patients would be so underserved, almost to the point of malpractice.”  

Dr. Lewis considers MRD testing a key part of his own standard of care and anticipates its broader adoption among GI oncologists. He also highlights the recent findings from the GALAXY study, which shows improved survival rates for patients utilizing MRD testing, underscoring its potential to reshape GI oncology practices in the near future.

Ed Abrahams has led the Personalized Medicine Coalition (PMC) for twenty years. Before his retirement in December, we asked him to join us to reflect on his tenure and take stock of the field. PMC was established as a “catalyst” and organizer to bring the various stakeholders in personalized medicine together and do the human work that science and business were missing.Ed tells Theral that the political problem may be more difficult than the science. Even with the scientific breakthroughs, he says that what Biden called his Cancer Moonshot has proved more difficult than actually going to the moon!Ed traces the field’s roots back to the groundbreaking announcement of the Human Genome Project and reflects on the significant strides in personalized drug development, which now represents over a third of recent drug approvals, as well as breakthroughs and difficulties on the diagnostics side.Current challenges are regulation in the second Trump era and the persistent practice gap, but Ed ends with excitement for what’s next.The Personalized Medicine Coalition hosts its annual conference in Boston this week, Nov 13-14th.  They have just announced their new president to be Amy Nicole Nayar, formerly Vice President for U.S. Patient Advocacy & Government Affairs at Novartis Gene Therapies

Williams and Ulivi share their latest research, highlighting how microRNA’s rise in cancer diagnostics parallels the evolution of fragmentomics, which analyzes cell-free and circulating tumor DNA. We explore the key differences between using RNA and DNA in biomarker development, the advancements in tools driving these discoveries, and the timeline for microRNA-based diagnostic tests to reach clinical practice.

“There’s a lot of potential,” says Ulivi, “but the challenge in translating this into clinical practice will be the standardization and normalization of the process."

Join us as we discuss the promise, obstacles, and future of microRNA in transforming how we diagnose and treat cancer.

To learn how Single Cell Discoveries (SCD), a contract research organization in Utrecht, the Netherlands, has scaled and innovated in this field, Theral sits down with Mauro Muraro, cofounder and CEO of SCD. Muraro discusses the company's origins as a small university lab and its rapid growth due to increasing demand for single-cell and multiomic applications in biotech and pharma.

The conversation delves into the transformative potential of single-cell technologies, addressing key topics like identifying rare cell types, single-cell atlases, and the challenges of handling the enormous data generated from these analyses. Muraro explains how Single Cell Discoveries is advancing the field with cutting-edge techniques, such as spatial transcriptomics and high-throughput sequencing, to push the boundaries of biological research and drug discovery.

Why does a single cell require such a large sequencing capacity? What are the challenges in finding new higher-quality targets for pharma?  And how does SCD aim to push the boundaries of current single-cell technologies?

One of the ways SCD helps pharmaceutical companies is by stratifying tissue by cell type to better find targets that will work. Muraro tells of a client working on neurodegenerative diseases who says, "It’s like doing a clinical trial in a dish."

Bajaj explains that at Xaira, machine learning and advanced modeling enable drug development to happen almost entirely in silico. By simulating biological systems and predicting drug interactions, AI could dramatically cut the time and cost of traditional methods.

However, there are still hurdles, especially the need for more robust genomic datasets to better understand causality. Bajaj discusses how Xaira Therapeutics is addressing this gap, driven by an ambitious vision to harness AI for breakthroughs that could reshape the field.

What are the most exciting applications of AI in biotech today? And what does Bajaj see as the biggest challenges ahead? We even ask for his thoughts on unified information theory—a concept that could integrate biology, AI, and computational science for a more comprehensive approach to human health.

Join us as we take a broad look into what’s happening now in AI-driven biotech with one of the field’s leading innovators.

At AGBT earlier this year, the company unveiled its latest offering in development, the G4X Spatial Sequencer, an upgrade to the G4 that unlocks the system to perform high-throughput in situ multiomics.  The platform will be capable of simultaneous direct RNA sequencing, targeted transcriptomics, proteomics, and fluorescent H&E from FFPE tissues at subcellular resolution. The G4X positions Singular to be the only company worldwide to offer capabilities for tissue-based in situ spatial multiomics and NGS on the same instrument.Singular's CEO, Drew Spaventa, joins us to discuss the G4X platform and the latest evolution in spatial biology.Drew says the field of spatial biology is a billion-dollar market, is growing rapidly, and the platform hits a sweet spot for throughput to bring down running costs. "The biggest issue people have right now in spatial is throughput cost per sample,” says Drew.  “It’s prohibitively expensive.”What early applications does the company see in their early service work?  When will the instrument be available?  And how does Drew see research evolving in the next couple years?

Ellen will be discussing this further with a panel at the upcoming Precision Oncology and Diagnostics 2024 in Chicago.

Udayan joins us today to describe the new instrument and comment on how sample prep is evolving today. Most importantly, the company wants to develop new apps with customized settings based on the customer's particular application, such as isolating really long, high-molecular-weight DNA for long-read sequencing. 

“The vision is to have a vast set of apps, similar to an iPhone.  We will continue to provide more and more apps that cater to various customers,” says Udayan in today’s show.

What are the apps Udayan sees in the next few years?  And what is the ultimate sample prep in today’s world of sequencing?

Chris Whelan was the lead author of this project paper, and he joins the show to discuss what’s next for these kinds of studies and their results. Whelan is a director of neuroscience on the data science and digital health team at Janssen Research & Development. He’s also chair and co-founder of the Pharma Proteomics Project.

A new blood collection device offered by startup company Tasso is a blood lancet that collects whole liquid blood samples. Its ease of use for at-home collection could dramatically improve patient testing compliance and impact the scale of clinical trials.Ben Casavant is the co-founder and CEO of Tasso. He joins us to discuss the possibilities for at-home testing.  Ben and the company have raised over $100 million dollars.

Kevin says at the core of the debate is the question of “the self" and whether it can be its own cause. Through several chapters, he develops the history of “motility” in life, the ability of single cells to move around.“The environment may be so inhospitable that you need to move, especially if you’ve been dividing and dividing and using up all the food. Being able to move is a really good trick, and then you must ask, well, where?  Which way should I move?  Moving toward a food source and away from a threat becomes selectable over time,” says Kevin.Does Kevin think of this single cell that has just learned to move as an "agent?”   (The Latin root for agent is “agere,” meaning to do, to move.) As life evolved, Kevin argues, it developed purpose and meaning which will guide it in a “top-down” way. What are the broad implications of Kevin’s work on free will for further study of biology and philosophy? How might his thinking extend to robots and AI?We finish with a discussion on reductive and non-reductive biology.Note: Coincidentally, another book written by a biologist arguing the other way on free will hit shelves at the same time Kevin’s book came out. In Determined: A Science of Life Without Free Will,  Stanford neuroscientist Robert Sapolsky uses biology to argue that we do not have free will. We have invited Robert to the program.

The gene linked phenotype to the molecules of chemistry and to the more abstract and promising world of information. 

There have been many great successes, from new understanding and treatment of cancer to gene therapy for sickle cell disease. There have also been many failures. Drugs flop and are not approved; diagnostics fall short; and much about our bodies remains shrouded in mystery. Over the years, we have heard that if DNA sequencing (the way we characterize genes and the genome) was much cheaper and we just did more of it, then we would solve the hard questions. 

In the meantime, some researchers are taking a new approach to biology. Many consider themselves non-reductionists, and they are looking for answers beyond the genome.Today, we begin our 14th season with a new series exploring these alternated approaches to biology with Michael Levin, a developmental and synthetic biologist and professor at Tufts University. Mike also directs the Allen Discovery Center and the Tufts Center for Regenerative and Developmental Biology and is co-director of the Institute for Computationally Designed Organisms.   He has a Wyss Institute appointment at Harvard.

Mike’s less traveled path is focused on the innate intelligence of tissues and organs. He argues that networks of cells are goal-oriented and achieve their goals through the medium of bioelectricity, a kind of proto-brain.   He knows that terms like "intelligence” and “goal” are taboo in the field and insists on fundamental basic definitions for the terms.  The idea is to go in and “reprogram” the goals of a group of cells and let them do the work of reversing disease.  Talk about gene therapy—Mike says he can imagine biological machines that are already in our bodies finding and repairing damaged DNA, tissue, and organs. Already, he has published work of reprogramming nematode worms to have two heads or to express their head on a different part of their bodies.  You can find over 300 publications on his website where he has painstakingly laid out his ideas and detailed his successes.

We’re very excited to get Mike on the show to discuss his work and the implications.  What response is he hearing from the research community? What is his roadmap for the future? Should there be a change in priorities among funding agencies such as NIH?  "I want to get across one very simple idea from which bioelectricity and a million other things flow—and I’m not the only one saying this—and that is the idea that the need to go down to the level of chemistry for understanding and control is just an assumption.  It is not necessarily the optimal level,” he says.

“In 2020, everything shut down because of COVID-19. It was a really interesting time to take care of cancer patients. One of our top priorities was to minimize cancer patient interaction in the clinic to avoid exposure to COVID-19. And that includes getting scans,” says Jurdi at the outset of today’s program.This was precisely when Natera’s ctDNA testing came on the market. Jurdi said it looked very promising, so he “dipped his toes in the water.” He soon saw that the ctDNA test was predicting what would happen several months before the scans would show anything and decided to use it across the board with his patients. Fast forward a year, and he would join Natera to get the chance to help shape the field.And how is ctDNA testing impacting cancer, particularly colorectal cancer, today? For what applications throughout treatment are oncologists using ctDNA testing? What are the results of some extensive ongoing studies? When might major guidelines include ctDNA testing as routine care?Jurdi says that 40 percent of oncologists are now using this testing from Natera, and “we’re just scratching the surface.”

Today researchers are largely on board with the amyloid cascade hypothesis. There are several FDA-approved drugs for treating the disease, with another just around the corner. New biomarkers for Alzheimer’s enabled by a new generation of proteomics tools promise to change care by giving patients the chance to be treated early before “the neural networks are too damaged.”

Henrik Zetterberg joins us to give an inside look at the exciting developments in Alzheimer’s. Zetterberg is a professor at the University of Gothenburg and one of the world’s leading experts in the field. He has been using innovative new technologies, including Alamar’s NULISAseq CNS Disease Panel, to help detect key and difficult-to-find protein biomarkers of neurodegeneration in blood.

“In the US, there are studies ongoing with people who do not have symptoms but are biomarker positive for Alzheimer’s pathology,” he says in the interview. “These studies are going to be so exciting because they answer the question, ‘If you remove amyloid before you have clinically significant neural network breakdown, will that stop the disease or slow it down?’”

After his summary of the field, Zetterberg ends with an appeal to the European Medical Agency: approve these new drugs. They’re working.

Kian joins us today to talk about his vision for the company and why consumer genomics is still a great idea.“To know that we can potentially give someone an insight that could save their life—that’s so powerful,” he says in today’s show. I’m excited to bring genomics to a wider audience than it’s ever been delivered to.  If you look at 23andMe and the other consumer companies, we’re talking about 14 to 15 million people.  The United States has over 300 million people.  There are hundreds of millions of people who have never done a genetic test.”What does the Nucleus testing process look like?  How is the company determining which variants and PRS scores to return?  What about recent LDT regulation implementation?According to Illumina, which partners with the new company, Nucleus raised 18 million in funding in 2022, largely from Reddit founder Alexis Ohanian’s venture capital firm, Seven Seven Six, and Peter Thiel’s Founders Fund. Kian is just twenty-four years old.  He says he became highly motivated to do something when a teenage cousin died suddenly in her sleep and her doctors attributed it to long QT syndrome.   “Hundreds of millions of people in the United States are carriers for a DNA variant that they do not know about.  There’s a narrative that consumer genetics is dying, but less than .001% of the population has done a whole genome test,” he says.  “There’s so much to build here."

Avi Veidman spent over 20 years in the IDF (Israel Defense Forces), leading multi-disciplinary teams in the use of AI, machine learning, and data science.  One of his key projects involved developing systems that mapped the world with satellite images to spot adversaries from space.  Upon retirement, he co-founded Nucleai with a couple of his former defense colleagues, believing that the AI technology they had seen and developed would be useful to a pathologist in tracking cancer.

Before founding Alamar, Luo was the founder and CEO of Advanced Cell Diagnostics, which was acquired by BioTechne in 2016. He was also a co-founder of Panomics, which was scooped up by Affymetrix.

Yuling recently lost his mother to cancer and feels the compelling case that we can do better with early detection. In founding Alamar, he realized this was really a technical problem.

He says that “liquid biopsy is quite popular, but the performance is limited. Detection for stage I cancer is 25 percent. That is not good enough. We need to get to 80 to 90 percent for it to really be meaningful. Why not use proteins for markers?" he asked. "There are hundreds of thousands to millions of copies of proteins. And proteins are more specific to tissue type.”

How does the new Alamar technology work and fit in the overall proteomics tools landscape? Yuling says it is more sensitive and able to detect 90 percent of the proteins in blood plasma, up from 50 percent with other tools. The new sensitivity comes from suppressing background noise 10,000 fold.

How is Alamar’s technology impacting research in the hot areas of Alzheimer’s and inflammatory disease? What is the overall opportunity with this new sensitivity? And what is the biggest challenge for the company over the next couple of years?

One might think the pandemic would have been good for diagnostic companies.  So why the financial hangover?Mara Aspinall has 30 years of leadership in genomics and the diagnostics industry.  This has led her to her current role as a new partner at Illumina Ventures, a venture fund independent from Illumina that is focused on funding diagnostics and tools companies.Mara publishes the fantastic newsletter Sensitive and Specific and also a yearly report on industry trends, which is the topic of our show today. We discuss valuations, new regulations, and the latest science. Mara co-founded the Biomedical Diagnostics master’s degree program at Arizona State University, the only program dedicated exclusively to diagnostics, genetics, and genomics.  How is the program faring, and how are we doing as a nation in educating the next generation on a revolution in diagnostic testing?

Bret Barnes has spent his career at Illumina developing the DNA methylation Infinium arrays that have become the workhorse of epigenomic studies around the world. Barnes says he was torn as a young person between biochemistry and computer science. He fortuitously ended up at UC Santa Cruz when they launched the first bioinformatics degree. Early on, he was interested in protein structure prediction.

“There are 20 amino acids,” he said. “Way more exciting than DNA with only four bases.”

But then he discovered the fifth base.

“Methylated cystine is the fifth base. So five, not four — a little better,” he continues. At the time of the Solexa acquisition, Illumina recruited Bret to do bioinformatics work on DNA methylation.

“If the king and queen of DNA methylation at Illumina were Kevin Gunderson and Marina Bibikova, then you could think of me as the prince or maybe the joker,” he says, tongue in cheek.

Where are we at today in epigenomics? What applications does Barnes see for the actionable epigenome, and how is the field developing?

Not content to offer “me too” products, a new company in the prenatal arena, Billion to One (BTO), is reimagining prenatal testing. Last year, their new Unity Fetal Risk Screen was featured in the American Journal of Human Genomics as a top advancement in applying genomics to clinical care. Joining us today is Jennifer Hoskovec, Senior Director of Medical Affairs at BTO. She says the new Unity Screen offers two steps in testing: the first screen and, if necessary, a risk assessment for the baby. These can both be done with a single blood draw from the mother. Up until now, the father’s DNA was needed as well as the mother’s to determine risk assessment. Because a sample of the father’s DNA may not be easily attainable or can just cost more, Jennifer says that the new Unity Screen is further democratizing prenatal testing.

Ever since the pandemic broke out, scientists, as well as policymakers, have been debating new restrictions on pathogen research, and last month, the White House released a new policy for what it calls “dual use research of concern and pathogens with enhanced pandemic potential.

Marc Lipsitch is Professor of Epidemiology and Director of the Center for Communicable Disease Dynamics at the Harvard Chan School of Public Health.  He joins us to talk about the pros and cons of the new policy and explain how it might work moving forward.

Marc acknowledges there is legitimate disagreement among scientists, but these are value-laden questions, so it's for more than scientists to decide. It should include ethicists and the public. What are some of these value-laden questions? Will this impact privately funded research, and what are some of the alternative possibilities to high-risk research?

Today, we pursue an exciting area of medicine for the first time:  cell therapy for solid tumors.Most, if not all, of our audience will be familiar with the success of CAR-T therapies for blood cancers.  But only 10% of cancer is in the blood.  The other 90% develop solid tumors. Jason Bock is the CEO and founder of CTMC, a new company aiming to speed the advancement of the entire field of cell therapies. First, we cover this new treatment for solid tumors and discuss the near-science-fiction action of tumor-infiltrating lymphocytes (til). 

Damon’s biography includes work at Celera in the age of the Drosophila and Human Genome papers and at a large community health system, Catholic Health Initiatives, where he was in charge of precision medicine.   At Illumina, he’s part of the large vision of seeing that genomic medicine has every chance at adoption.Today, we ask Damon what has changed about access to genomic testing in the past five years and where we are seeing success. Damon brings a refreshingly optimistic viewpoint to the show. We talk about everything from PGx testing to whole genome sequencing, which he calls an “amazing win” for reimbursement.

Sarah LeBaron von Baeyer studied anthropology at Yale. Today she serves as the Director of Ethics Engagement at the new drug development company, Variant Bio, not a job she ever imagined at university.

"We lack a way of training genomics AI as readily as you would for natural language processing, says Fahr.  "There are vast amounts of data, but there are no labels, no supervision.  One of the most powerful tools that we’ve found is using clues from natural selection.

Fahr says the company began the AI lab seven years ago when deep learning took off. Two of the team’s AI algorithms, PrimateAI-3D and SpliceAI, published in Cell and Nature Genetics, were among the first examples of deep learning algorithms in genomics to become widely used by clinical labs and researchers in interpreting variants of unknown significance.  

We take a close look at Illumina’s work in AI and delve into the long-term impact of AI on genomics.

Today, we continue our look into the gap in the adoption of precision medicine. Why are those who need it not getting genetic testing? Patrick Short is the Host of The Genetics Podcast and CEO and Co-founder of Sano Genetics.

Through its Center for Personalized Medicine, the University of Colorado Health offers its 2.2 million patients some of the country's most advanced precision medicine initiatives.

A  new spatial biology company is promising to shake up the field. Last month, Curio Bioscience launched a new technology to early access customers that provides transcriptomic spatial data without the need to b…

While 2024 saw a total investment of over $6 billion (not as high as the pandemic year of 2021), John says the new technologies and startups keep coming.

"We’re seeing just a ton of new entrepreneurs coming out of graduate and undergraduate programs and starting companies.”

John is the founder and CEO of SynBioBeta which takes place May 6-9th in the San Jose Convention Center.

Today, we feature a new DNA synthesis company out of Sweden that is making a name with long, single-stranded DNA at scale. How long? Over 10,000 bases. Why single-stranded vs. genes? And what is meant by scale?According to Cosimo Ducani, CEO and co-founder of Moligo Technologies, the business of making DNA is just getting started.  So much for thinking it was a mature business in the early 2000s when Integrated DNA Technologies (IDT) dominated the market.

Chapters:

0:00 Number one unmet medical need for dogs

6:25 Using “extra label” for cross species

12:57 Ideal for understanding human cancers

21:25 Playing catch-up with human medicine

28:04 1,000 pet clinic customers

Precision medicine for dogs?— as in tumor profiling for the right therapies to treat man’s best friends at the right time? Yes, that’s right. …

0:00 Long reads at scale has made what difference?6:15 The long or short of it:  How does one decide?12:31 Long reads in the clinic20:37 Apton tech to compete with Illumina’s NovaSeq X26:30 Plans for next instruments35:00 Surveying the competitionIn our first post-AGBT show of the year, we’re talking with the CEO of Pacific Biosciences, Ch…

Fun fact:  we are composed of 90% bacterial cells and 10% human cells.  Surely, the company that begins to turn that knowledge into health products will be the next billion-dollar startup. Pendulum Therapeutics is doing just that.  Started in 2012, the company now boasts a full product line of probiotics that are not your typical probiotics.  In 2020, the company released a scientific study showing that their glucose control product lowered blood glucose spikes by 30%.“It’s the first microbiome product that has shown that kind of efficacy,” says Pendulum CEO Colleen Cutcliffe.  “We did a placebo-controlled double-blind, randomized trial that showed that compared to placebo, people who were on this formulation could see their A1C go down by 0.6 points, which can be the difference between having diabetes or not.”Colleen is a return champion here on the show, and it’s great to see the company raising real money and pioneering the microbiome space with credibility.  Will naturally occurring probiotics become the next breakthrough in therapeutics?  We’re talking about the "safety of a probiotic with the efficacy of a drug."

"We can now begin to look at disease before it happens,” says today’s guest, Todd Druley.  He’s the Chief Medical Officer at Mission Bio who has been offering the world’s first single cell and multi-omics instrument. 

Many of our shows this year have explored a new wave of proteomics tools and research.  So today, we wanted to get a snapshot of the field of proteomics, and to do that, we turned to John Yates III, Ernest W. Hahn Professor at The Scripps Research Institute.  John was on the proteomics side of the famous Lee Hood lab in the 1980s.  The most exciting work to come out of Hood’s lab was the first automated DNA sequencer commercialized by Applied Biosystems and led by Mike Hunkapillar, also from the lab.

This month, a new philosophy of biology series premiers on PBS hosted by Robert Lawrence Kuhn.  The series will go for thirteen episodes and includes over 250 interview clips with some of the world’s leading biologists and philosophers, including Richard Dawkins, Terrence Deacon, Peter Godfrey Smith, and Samir Okasha. Show titles include: Why Philosophy of Biology?, Philosophy of Units/Levels of Natural Selection, and Philosophy of Sex and Gender.Robert joins us today to preview the series, his first in 25 years on biology.  At the heart of the interview is a discussion of reductionism and emergence,  a familiar subject for this show. 

John Shon is the Chief Technology Officer at Serimmune, a company specializing in precision immunology.  Serimmune maintains a library of over 10 million random peptides that can mimic almost any disease.  With this library, they are able to comprehensively map the relationship between antibodies and antigens.What does this mean?  Take COVID, for instance; rather than just offering a diagnostic, Serimmune can show disease history in the body.  They partnered with Moderna to look at the epitopes from their vaccines and boosters.  For those patients who took vaccines, the company saw a different and more focused response to the COVID-19 virus.This is a comprehensive measuring of human immunity.  The technology can be used with almost any disease.  And it picks up cross-disease interactions. So, where is the company today?  And how does John see their powerful technology being adopted in medicine?

Personalis, a company launched during the early days of whole genome testing and analysis, is claiming to have the most sensitive MRD testing available to date.  They are demonstrating this with the results of their recently released TRACERx study of patients with non-small cell lung cancer. CEO Chris Hall and CMO Rich Chen both join us to profile these exciting results and debut the entrance of Personalis into MRD testing. “This test is 10 to 100 times more sensitive than other tests,” says Rich Chen.  “And so how do we do this?  We’re creating a personalized test for each and every cancer patient.”First making their name in whole genome analysis, Personalis is not only looking at the ctDNA but also sequencing the tumor for each test.   The test is available now.  While the technology is validated for all cancers, Rich and John say they are going after the hardest-to-detect cancers first. What is their goal for the next two years, and how will the company push up the low rate of adoption in the field?   Join us for a comprehensive interview into the next generation of MRD testing.

Chapters:

0:00 Delivering on last year’s announcements

8:50 Illumina

14:25 Long reads

25:50 PacBio vs Oxford Nanopore

31:36 Element

38:27 MGI

45:47 The rise of proteomics

51:20 What next?

The end of the year approaches, and we look back today on the state of DNA sequencing with two of our return champions, Shawn Baker, genomics consultant, and…

0:00   State of the field: reviewing ICoNS conference

22:20 What evidence is enough?

Today, we’re joined by a panel of four guests who have all attended the recent International Conference on Newborn Sequencing held at the Royal Institution in London.  This discussion serves as the second part in a series we are co-producing with GenomeWeb that began with last month’s panel.  At the conference, researchers representing 12 newborn sequencing research programs in the US, the UK, Europe, Australia, and the Middle East discussed their progress to date and future plans.   It’s our good fortune to hear about the conference and get some thoughts on the field going forward.  Julia Karow is the Managing Editor at GenomeWeb, who tracks trends in next-gen sequencing for research and clinical applications.Robert Green is a physician-scientist who directs the Genomes2People Research Program in translational genomics and health outcomes.  He also co-chairs the International Consortium on Newborn Sequencing, the group which hosted the conference.Wendy Chung is Chair of Pediatrics in Medicine at Boston Children’s Hospital.  She directs one of the largest newborn sequencing studies,  called the Guardian Study.James Buchanan is a Senior Lecturer in Health Economics at Queen Mary University in London.  He does research into the health economics of precision medicine and genetic testing, including newborn screening.

Chapters:0:00 Precision oncology is standard of care13:50 Culmination Bio23:25 Hopeful about early cancer screening25:45 Biggest challenge for the field?When Lincoln Nadauld began Precision Genomics at Utah-based Intermountain Healthcare, he told the administrators that precision oncology is coming and will be standard of care. He urged them to d…

Chapters:0:00 What are transcription factors?7:00 The MARMOT platform11:22 In the ’90s, people thought kinases were undruggable19:00 Where’s the company at today?

We begin today’s show with definitions.  What are transcription factors?  What is functional proteomics?  And what is meant by “undruggable?"According to a study in Nature from las…

Chapters:0:00 Attending this year’s Human Proteome Organization (HUPO) conference4:40 Mass spec vs. sequencing8:12 How does the Orbitrap Astral fit into the market?12:55 Customer applications

Thermo Fisher Scientific is a name synonymous with life science tools.  They have been at the vanguard of every important trend in our field for decades.…

Chapters:0:00 What does treatment look like?7:25 Light treatment has been approved for years20:10 Could this be a primary therapy for all cancers?25:05 Challenges?

We often cover new therapies for cancer.  They are usually derived from “chemistry."  But what about using “physics” in a non-invasive way for treatment?  A new company named SonA…

Today’s show is made free through the generous support of Seer. For decades, a limiting factor in proteomics research has been the inability to access the proteome in ways necessary to survey and understand its diversity. So, Seer created their new Proteograph(TM) to provide a more transformative lens of the proteome.

Chapters:0:00 Pet dogs have complex genetics and phenotypic data8:00 What is the primary interest of pet owners?16:00 Breeds are relatively new—Victorian era new25:53 Findings that relate to human genetics34:00 Future goalsSummary:Elinor Karlsson began studying pet genetics when doing her PhD.  Today she directs the largest pet dog genetics databases and citizen science projects, Darwin’s Ark (www.darwinsark.org). Elinor is a Professor at UMass Chan and the Broad Institute.Why dogs?  Well, she works specifically with pet dogs who are tied to humans.  Dog owners love learning about their dogs--breed, behavior, anything—almost as much as they love sharing about them.  This opens up an opportunity for researchers to study an animal with complex genetics which also has tons of phenotypic data recorded.

 So what is Elinor able to tell these pet-loving owners?  How is the project improving dog medicine?  And what is canine genetics teaching us about us?

Mendelspod is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.

Chapters:

0:00 World’s longest oligo

8:45 Why is it difficult to synthesize long DNA?

12:00 Proprietary TdT conjugate

16:00 A billion-dollar market

24:20 The computation model and its challenges

28:35 More customers using generative AI

Mendelspod is now reader supported. Please consider upgrading to a paid subscription for the price of a couple cof…

Chapters:0:00 Novel Cas enzymes help overcome CRISPR challenges11:37 New pipeline of therapies will go after novel targets14:52 How does the new platform open up possibilities for new diagnostics?21:05 What risks do you think about?26:47 What are the company’s two-year goals?31:07 On the possibilitiesCRISPR technology is enabling a new generation …

0:00 Latest paper on multi-omics microsampling6:30 Is it useful?  Two scenarios13:00 How might entrepreneurs bring this to healthcare?18:15 How do you convince physicians?25:48 Are you a reductionist?31:00 Impact of generative AI38:15 Thoughts on the renaissance in proteomics

We open our 13th season here at Mendelspod with guest, Mike Snyder, S…