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PODCAST

Base by Base

Base by Base explores advances in genetics and genomics, with a focus on gene-disease associations, variant interpretation, protein structure, and insights from exome and genome sequencing. Each episode breaks down key studies and their clinical relevance—one base at a time. Powered by AI, Base by Base offers a new way to learn on the go. Special thanks to authors who publish under CC BY 4.0, making open-access science faster to share and easier to explore.

science life sciences

All Episodes

00:19:13

175: Predictive Prioritization of Pancreatic...

Base by Base ·

2025/10/22

️ Episode 175: Predictive Prioritization of Pancreatic Enhancers Linked to Disease Risk In this episode of PaperCast Base by Base, we explore how enhancer–promoter 3D chromatin maps from five primary human pancreatic cell types were transformed into graph “tree” models to quantify enhancer connectivity and prioritize elements most critical for cell-type-specific gene expression, creating a framework to connect noncoding variants to function in pancreatic

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00:16:40

174: TMEM217–SLC9C1: Wiring the cAMP Switch for Sperm...

Base by Base ·

2025/10/21

️ Episode 174: TMEM217–SLC9C1: Wiring the cAMP Switch for Sperm Motility and Male Fertility In this episode of PaperCast Base by Base, we explore a PNAS study revealing how TMEM217 forms a complex with the sperm-specific Na+/H+ exchanger SLC9C1 to organize cAMP signaling, sustain motility, and enable fertilization in mice. Study Highlights:Using phylogenetic profiling and interactomics, the authors identified TMEM217 as a conserved partner of the

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00:20:12

173: Bottlebrush Block Copolymer Shields Muscles and...

Base by Base ·

2025/10/20

️ Episode 173: Bottlebrush Block Copolymer Shields Muscles and Prevents DMD Onset In this episode of PaperCast Base by Base, we explore a PNAS study showing how a synthetic bottlebrush block copolymer can act as a powerful membrane stabilizer to protect dystrophin-deficient muscle in Duchenne muscular dystrophy. Study Highlights:Researchers engineered and tested an amphiphilic bottlebrush diblock polymer, B–PEO43_10–PPO15_5, as a membrane stabilizer in

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00:19:44

172: When Random DNA Fights Back: De Novo Gene Birth...

Base by Base ·

2025/10/19

️ Episode 172: When Random DNA Fights Back: De Novo Gene Birth as Antiphage Defense In this episode of PaperCast Base by Base, we explore a PNAS study showing that short, previously nongenic DNA sequences can quickly evolve into genes that help bacteria survive phage attack, illuminating early steps of gene birth and the host–virus arms race. fileciteturn2file0 Study Highlights:The authors screened two massive libraries totaling ~100 million

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00:16:14

171: Virulence Hierarchies in the Tuberculosis...

Base by Base ·

2025/10/18

️ Episode 171: Virulence Hierarchies in the Tuberculosis Complex—What Makes Some Lineages Deadlier? In this episode of PaperCast Base by Base, we explore a new PNAS study that directly compares the virulence of Mycobacterium tuberculosis, M. bovis, and M. orygis across natural and laboratory hosts to uncover why animal-adapted lineages can be so devastating. Study Highlights:The authors performed side-by-side infections in Holstein calves and C57BL/6

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00:17:03

170: Maternal Age, Meiotic Recombination Failure, and...

Base by Base ·

2025/10/17

️ Episode 170: Maternal Age, Meiotic Recombination Failure, and Triploidy in Humans In this episode of PaperCast Base by Base, we explore how maternal age and failures of meiotic recombination shape the origins of triploid conceptions in humans, drawing on large-scale preimplantation genetic testing datasets from ICSI-derived embryos. Study Highlights:Drawing on 96,660 embryo biopsies with an independent validation cohort of 44,324, the authors quantify

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00:17:03

170: Maternal Age, Meiotic Recombination Failure, and...

Base by Base ·

2025/10/17

️ Episode 170: Maternal Age, Meiotic Recombination Failure, and Triploidy in Humans In this episode of PaperCast Base by Base, we explore how maternal age and failures of meiotic recombination shape the origins of triploid conceptions in humans, drawing on large-scale preimplantation genetic testing datasets from ICSI-derived embryos. Study Highlights:Drawing on 96,660 embryo biopsies with an independent validation cohort of 44,324, the authors quantify

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00:21:13

169: Deep mutational scanning of the insulin receptor...

Base by Base ·

2025/10/16

️ Episode 169: Deep mutational scanning of the insulin receptor guides precision therapy for insulin resistance In this episode of PaperCast Base by Base, we explore how a comprehensive deep mutational scan of the human insulin receptor ectodomain maps the effects of ~14,000 missense variants on surface expression, insulin binding, and downstream signalling, creating a sequence–function atlas to improve diagnosis and treatment of severe insulin

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00:19:10

168: Low circulating miR-190a-5p predicts progression...

Base by Base ·

2025/10/15

️ Episode 168: Low circulating miR-190a-5p predicts progression of chronic kidney disease In this episode of PaperCast Base by Base, we explore how unbiased small RNA sequencing and multi-cohort validation identify circulating miR-190a-5p as a prognostic marker of chronic kidney disease that reflects tubular health and points to a potential therapeutic strategy. Study Highlights:Using small RNA-sequencing of plasma from people with and without CKD in

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00:21:40

167: DeepScence: Detecting Senescent Cells at...

Base by Base ·

2025/10/14

️ Episode 167: DeepScence: Detecting Senescent Cells at Single-Cell and Spatial Resolution In this episode of PaperCast Base by Base, we explore a Cell Genomics study introducing DeepScence, a deep-learning autoencoder that leverages a compact “CoreScence” gene set to identify senescent cells across single-cell and spatial transcriptomics data, outperforming marker- and gene set–based approaches. Study Highlights:The authors systematically compared nine

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00:13:37

166: Molecular Squeezing: How Coronin, Cofilin, and...

Base by Base ·

2025/10/13

️ Episode 166: Molecular Squeezing: How Coronin, Cofilin, and AIP1 Rapidly Disassemble Actin Filaments In this episode of PaperCast Base by Base, we explore a Cell study that uses single-particle cryo-EM to reveal the stepwise, synergistic mechanism by which coronin, cofilin, and AIP1 drive rapid actin filament disassembly in eukaryotic cells. Study Highlights:The authors solve a series of cryo-EM structures showing that coronin binds cooperatively to

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00:19:24

165: Protist Genomics: Key to Understanding...

Base by Base ·

2025/10/12

️ Episode 165: Protist Genomics: Key to Understanding Eukaryotic Evolution In this episode of PaperCast Base by Base, we explore how accelerating protist genomics—spanning single-cell approaches, metagenomics, and long-read assemblies—unlocks deep insights into eukaryotic evolution, symbiosis, organelle origins, ecosystem dynamics, and the methodological shifts needed to go beyond plant/animal-centric standards. Study Highlights:This review argues that

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00:14:46

164: m6A in the coding sequence: linking deposition,...

Base by Base ·

2025/10/11

️ Episode 164: m6A in the coding sequence: linking deposition, translation, and decay In this episode of PaperCast Base by Base, we explore how N6-methyladenosine (m6A) marks within coding sequences orchestrate a fast, translation-coupled route to mRNA decay, and how splicing- and chromatin-linked mechanisms shape where those marks are placed across transcripts. Study Highlights:The authors synthesize recent mapping and mechanistic studies to show that

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00:14:46

164: m6A in the coding sequence: linking deposition,...

Base by Base ·

2025/10/11

️ Episode 164: m6A in the coding sequence: linking deposition, translation, and decay In this episode of PaperCast Base by Base, we explore how N6-methyladenosine (m6A) marks within coding sequences orchestrate a fast, translation-coupled route to mRNA decay, and how splicing- and chromatin-linked mechanisms shape where those marks are placed across transcripts. Study Highlights:The authors synthesize recent mapping and mechanistic studies to show that

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00:14:18

163: Animal origins: looping back in time

Base by Base ·

2025/10/10

️ Episode 163: Animal origins: looping back in time In this episode of PaperCast Base by Base, we explore how chromatin folding mechanisms emerged alongside animal evolution, focusing on a Spotlight article that synthesizes high-resolution 3D genome maps across unicellular relatives of animals and early-branching metazoans to probe when enhancer–promoter looping first appeared. Study Highlights:This Spotlight reviews evidence from micro-C datasets

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00:20:15

162: Spatially Resolved microRNA Expression in...

Base by Base ·

2025/10/09

️ Episode 162: Spatially Resolved microRNA Expression in Tissues: Technologies, Challenges, and Opportunities In this episode of PaperCast Base by Base, we explore how emerging “spatial miRNomics” methods map microRNA expression directly within intact tissues, revealing cell- and region-specific regulatory patterns that bulk and even single-cell assays can miss. Study Highlights:This review charts the field from established singleplex imaging with LNA

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00:20:55

161: Decoding Genomic Landscapes of Introgression

Base by Base ·

2025/10/08

️ Episode 161: Decoding Genomic Landscapes of Introgression In this episode of PaperCast Base by Base, we explore how modern population genetics dissects the genomic footprints of introgression across species, reviewing summary statistic approaches, probabilistic modeling, and supervised learning, and showing how these methods reveal adaptive and ghost introgression and the functional roles of introgressed loci. Study Highlights:The authors organize the

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00:15:36

160: The Long‑Read Leap in Single‑Cell Omics

Base by Base ·

2025/10/07

️ Episode 160: The Long‑Read Leap in Single‑Cell Omics In this episode of PaperCast Base by Base, we explore how long‑read, single‑molecule sequencing has collided with single‑cell technologies to illuminate “dark” regions and events in the genome, epigenome, and transcriptome that short reads routinely miss. Study Highlights:This review maps the rapid maturation of Pacific Biosciences and Oxford Nanopore platforms alongside single‑cell methods, showing

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00:15:56

159: The Untapped Potential of Short‑Read Sequencing...

Base by Base ·

2025/10/06

️ Episode 159: The Untapped Potential of Short‑Read Sequencing in Biodiversity Research In this episode of PaperCast Base by Base, we explore how modern short‑read sequencing and genome skimming are reshaping biodiversity science—from rapid species identification and biomass estimation to scalable phylogenomics and holobiont studies—while keeping costs and sample requirements low. Study Highlights:This review synthesizes how low‑coverage short‑read data

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00:15:23

158: Interruptions in Repeat Expansion Diseases: How...

Base by Base ·

2025/10/05

️ Episode In this episode of PaperCast Base by Base, we explore how small sequence changes—“interruptions”—within expanded tandem repeats shape the onset and severity of repeat expansion disorders, and a new mechanistic model that may explain how these interruptions are gained and lost across generations. Study Highlights:Interruptions within repeat tracts can dampen somatic expansion and shift clinical trajectories, helping to explain variability in

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424 results

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