The Genetics Podcast

This week on The Genetics Podcast, Patrick is joined by Dr. Jeffrey Barrett, Group Leader at the Ellis Institute Finland and the University of Helsinki. They discuss using AI and federated biobank data to stratify common chronic diseases, how LLMs reading clinical notes in Finland's health registries can reveal treatment response, how AI is changing the way scientists research and train, and what the UK's COVID genome sequencing effort means for biosecurity.Show Notes0:00 Intro to The Genetics Podcast01:00 Welcome to Jeff 02:08 Jeff's research focus for his new lab, including molecular subtyping of common chronic diseases with AI06:18 Barriers to pooling biobank data across research environments for federated AI models11:00 Why Jeff expects larger datasets to make complex models better at predicting disease13:34 The three disease areas Jeff's lab will target first: cardiometabolic, inflammatory and neuropsychiatric19:41 Using LLMs to read clinician notes in Finland's health registries for treatment response24:50 How Jeff uses AI in his research and where humans still need to read and review31:08 Using Claude to understand papers and the gaps in its literature searches32:14 Jeff on AI solving open problems in mathematics and biology, and where researchers fit35:48 Simultaneous discoveries and why lab data generation still needs experts39:01 Jeff's COVID genome sequencing at Sanger and what it means for AI and biosecurity43:16  Closing remarks

SummaryThis week on The Genetics Podcast, Patrick is joined by Jenny Hsieh, Co-Founder and President of the Danon Foundation. They discuss how Danon disease affects males and females, why it is so often misdiagnosed, the current therapy landscape and research priorities, and how families can make informed decisions about gene therapy trials.Show Notes0:00 Intro to The Genetics Podcast00:59 Welcome to Jenny 01:28 An overview of Danon disease02:34 Sex differences in Danon disease and severe disease in females05:15 Why Danon disease is misdiagnosed and how it may be spotted earlier08:50 Therapy pipeline for Danon and the Foundation's global patient coordination13:46 Origin story of the Danon Foundation18:10 Research priorities and the burden of Danon disease beyond the heart22:39 Raising genetic testing awareness among ophthalmologists and cardiologists for Danon disease25:20 Recognizing broader Danon symptoms and launching the first Danon Awareness Day29:37 Informed consent and trial literacy for families weighing gene therapy33:14 Patient-friendly trial experiences36:19 Ways to support Danon research37:37 Closing remarksFind out moreDanon Foundation

This week on The Genetics Podcast, Patrick is joined by Dr. Inigo Martincorena, Group Leader at the Wellcome Sanger Institute. They discuss the discovery of widespread cancer-driver mutations in normal tissue, the role of somatic mutations in autoimmune disease, new sequencing technologies transforming the field, and the therapeutic potential of targeting these mutations.Show Notes0:00 Intro to The Genetics Podcast00:59 Welcome to Inigo 01:46 How Inigo's eyelid skin study revealed widespread cancer-driver mutations07:14 Findings from a follow-up study on esophageal tissue10:02 How NanoSeq technology scaled somatic mutation research across tissues12:34 The thyroid study linking somatic mutations to autoimmune disease17:07 How escaped B cell clones evolve into polyclonal autoimmune disease20:21 Immune gene mutations occurring in healthy aging lymphocytes21:21 Why driver mutation clones in normal tissue rarely become cancer24:16 Two therapeutic paradigms for targeting somatic mutations in disease28:13 Examples of somatic rescue mutations in the colon, liver, and blood29:20 Why clonal selection only occurs in dividing cell types31:20 The field's remaining blind spots in mobile immune cells and rare samples33:46 How new single-cell sequencing will link genotype to phenotype36:03 What Inigo has learned from collaborating across Sanger's expertise38:09 Closing remarksFind out moreEyelid studyEsophagus study

This week on The Genetics Podcast, Patrick is joined by Dr. Marleah Dean Kruzel, Professor of Communication at the University of South Florida. They discuss her personal path from watching breast cancer move through her family to testing positive for a hereditary mutation herself, the ART framework she developed for managing uncertainty, and the complexities of communicating genetic risk within families.Show Notes0:00 Intro to The Genetics Podcast00:59 Welcome to Marleah01:35 Marleah's family history of breast cancer across four generations02:48 Marleah's childhood living through her mother's five-year cancer battle04:26 Marleah's experience with genetic testing07:19 How a positive test result reshaped Marleah’s PhD research focus08:40 The central challenges of living with a positive test result 10:50 The ART framework for managing hereditary cancer uncertainty15:06 Applying the ART framework to Patrick’s experience with uncertainty and the importance of having a support system 19:53 Common misconceptions in how families communicate genetic risk23:54 The previvor identity and the chronic uncertainty it brings25:40 How Marleah has learned to accept and embrace uncertainty27:57 Balancing logic and emotion in hereditary cancer family planning31:28 How Marleah grounds her research tools in patients' lived experience33:21 How AI is eroding our capacity to sit with uncertainty35:57 Redesigning healthcare for a lifespan of genetic risk information38:10 Closing remarks

This week on The Genetics Podcast, Patrick is joined by Dr. David Hallett, Chief Scientific Officer at Recursion. They discuss the biggest shifts in drug discovery over Dave's three-decade career, where AI is genuinely transforming the field today versus where the hype outruns the reality, and how Recursion's perturbational maps have uncovered and validated a novel neurodegeneration target.Show Notes0:00 Intro to The Genetics Podcast01:00 Welcome to Dave01:57 The biggest shifts in drug discovery over three decades06:39 Where AI is delivering real wins across drug discovery today12:19 How AI-assisted trial simulation reveals which eligibility criteria to relax14:46 The three biggest reasons drug programs fail in the clinic 18:20 How Recursion's perturbational maps uncover new drug targets24:58 A four-step framework for validating a novel drug target28:44 How Recursion balances deep therapeutic focus with partnership breadth30:52 Why AI can't shortcut clinical trials, and what proof of real impact looks like34:57 The skills scientists need most in the AI era, and why trusting AI outputs starts with trusting the data39:52 Closing remarksFind out more:Recursion (https://www.recursion.com/)