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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

00:19:32

🎙️ 43: Personalized Molecular Signatures of Insulin...

Base by Base ·

2025/06/11

🎙️ Episode 43: Personalized Molecular Signatures of Insulin Resistance and Type 2 Diabetes🧬 In this episode of Base by Base, we explore the groundbreaking work by Kjærgaard et al. (2025) in Cell, where cutting-edge proteomics and phosphoproteomics were applied to skeletal muscle biopsies from over 120 participants with normal glucose tolerance or type 2 diabetes. By combining hyperinsulinemic-euglycemic clamps with deep in vivo phenotyping, the study maps fasting and insulin-stimulated protein and

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00:23:35

️ 42: Amino Acids Catalyse RNA Formation — Unlocking...

Base by Base ·

2025/06/11

️ Episode 42: Amino Acids Catalyse RNA Formation — Unlocking Prebiotic Cross-Catalysis In this episode of Base por Base, we delve into the groundbreaking 2025 Nature Communications study by Rout et al., which uncovers how simple amino acids, under ambient alkaline dry conditions, act as potent acid-base catalysts to drive non-enzymatic RNA oligomerisation from ribonucleoside-2′,3′-cyclic phosphates . Principais destaques:Amino acids elevate RNA oligomer

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00:23:34

🎙️ 42: Amino Acids Catalyse RNA Formation — Unlocking...

Base by Base ·

2025/06/11

🎙️ Episode 42: Amino Acids Catalyse RNA Formation — Unlocking Prebiotic Cross-Catalysis🧬 In this episode of Base por Base, we delve into the groundbreaking 2025 Nature Communications study by Rout et al., which uncovers how simple amino acids, under ambient alkaline dry conditions, act as potent acid-base catalysts to drive non-enzymatic RNA oligomerisation from ribonucleoside-2′,3′-cyclic phosphates .🔍 Principais destaques:Amino acids elevate RNA oligomer yields by more than 100-fold at pH

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00:18:42

🎙️ 41: Public Preferences for Genomic Newborn...

Base by Base ·

2025/06/10

🎙️ Episode 41: Public Preferences for Genomic Newborn Screening in Australia — Insights from Discrete Choice Experiments🧬 In this episode of Base by Base, we discuss a landmark study by Peters et al. (2025) in The American Journal of Human Genetics, which surveyed 2,509 members of the Australian public to uncover how people value and would like to see genomic newborn screening (gNBS) implemented .🔍 Highlights of the Study: Through two discrete choice experiments, the authors demonstrated that

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00:18:43

️ 41: Public Preferences for Genomic Newborn...

Base by Base ·

2025/06/10

️ Episode 41: Public Preferences for Genomic Newborn Screening in Australia — Insights from Discrete Choice Experiments In this episode of Base by Base, we discuss a landmark study by Peters et al. (2025) in The American Journal of Human Genetics, which surveyed 2,509 members of the Australian public to uncover how people value and would like to see genomic newborn screening (gNBS) implemented . Highlights of the Study: Through two discrete choice

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00:17:43

️ 40: Lysosomal Proton Leak — Uncovering SLC7A11’s...

Base by Base ·

2025/06/09

️ Episode 40: Lysosomal Proton Leak — Uncovering SLC7A11’s Role as an Unconventional H⁺ Transit Pathway In this episode of Base by Base, we delve into a revealing study by Zhou et al. (2025) in Cell that identifies SLC7A11—long known for its function in redox homeostasis and ferroptosis—as a slow H⁺ transporter embedded in lysosomal membranes. Through a combination of CRISPR knockouts, pharmacological inhibition, ratiometric pH imaging, and assays on

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00:17:42

🎙️ 40: Lysosomal Proton Leak — Uncovering SLC7A11’s...

Base by Base ·

2025/06/09

🎙️ Episode 40: Lysosomal Proton Leak — Uncovering SLC7A11’s Role as an Unconventional H⁺ Transit Pathway🧬 In this episode of Base by Base, we delve into a revealing study by Zhou et al. (2025) in Cell that identifies SLC7A11—long known for its function in redox homeostasis and ferroptosis—as a slow H⁺ transporter embedded in lysosomal membranes. Through a combination of CRISPR knockouts, pharmacological inhibition, ratiometric pH imaging, and assays on isolated lysosomes, the authors demonstrate

en-us

00:19:14

🎙️ 39: Whole-Genome Polygenic Score Inference — Fast...

Base by Base ·

2025/06/07

🎙️ Episode 39: Whole-Genome Polygenic Score Inference — Fast and Memory-Efficient Algorithms for Scalable PRS🧬 In this episode of Base by Base, we dive into the methodological breakthroughs of Zabad et al. (2025) in The American Journal of Human Genetics, where the authors introduce an updated variational inference framework (VIPRS v0.1) and novel data structures that together enable polygenic risk score computation across tens of millions of variants with dramatically reduced runtime and memory

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00:19:15

️ 39: Whole-Genome Polygenic Score Inference — Fast...

Base by Base ·

2025/06/07

️ Episode 39: Whole-Genome Polygenic Score Inference — Fast and Memory-Efficient Algorithms for Scalable PRS In this episode of Base by Base, we dive into the methodological breakthroughs of Zabad et al. (2025) in The American Journal of Human Genetics, where the authors introduce an updated variational inference framework (VIPRS v0.1) and novel data structures that together enable polygenic risk score computation across tens of millions of variants with

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00:20:28

🎙️ 38: Viral Journeys — Tracing the Ancestral Bat...

Base by Base ·

2025/06/07

🎙️ Episode 38: The Recency and Geographical Origins of Bat Viruses Ancestral to SARS-CoV and SARS-CoV-2🧬 In this episode of Base by Base, we delve into a landmark study by Pekar et al. (2025) in Cell that harnesses recombination-aware phylogenetic and spatial analyses to trace how the closest bat coronavirus ancestors of SARS-CoV-1 and SARS-CoV-2 circulated mere years before spilling over into humans. By dissecting non-recombinant genomic segments and applying tailored molecular clock models, the

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00:20:29

️ 38: Viral Journeys — Tracing the Ancestral Bat...

Base by Base ·

2025/06/07

️ Episode 38: The Recency and Geographical Origins of Bat Viruses Ancestral to SARS-CoV and SARS-CoV-2 In this episode of Base by Base, we delve into a landmark study by Pekar et al. (2025) in Cell that harnesses recombination-aware phylogenetic and spatial analyses to trace how the closest bat coronavirus ancestors of SARS-CoV-1 and SARS-CoV-2 circulated mere years before spilling over into humans. By dissecting non-recombinant genomic segments and

en-us

00:23:06

🎙️ 37: Proteomic Clues — Prioritizing Functional...

Base by Base ·

2025/06/06

🎙️ Episode 37: Proteomic Clues — Prioritizing Functional Missense Variants with Chemoproteomics🧬 In this episode of Base by Base, we highlight a new study by Palafox et al. (2025) in The American Journal of Human Genetics that bridges mass spectrometry-based chemoproteomics with variant interpretation. Missense variants—abundant and often challenging to classify—are prioritized here using measurements of amino acid reactivity, offering a protein-centric lens for clinical genomics. The authors

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00:23:07

️ 37: Proteomic Clues — Prioritizing Functional...

Base by Base ·

2025/06/06

️ Episode 37: Proteomic Clues — Prioritizing Functional Missense Variants with Chemoproteomics In this episode of Base by Base, we highlight a new study by Palafox et al. (2025) in The American Journal of Human Genetics that bridges mass spectrometry-based chemoproteomics with variant interpretation. Missense variants—abundant and often challenging to classify—are prioritized here using measurements of amino acid reactivity, offering a protein-centric

en-us

00:18:30

🎙️ 36: Bi-allelic POPDC2 Variants: A Novel Autosomal...

Base by Base ·

2025/06/06

🎙️ Episode 36: Bi-allelic POPDC2 Variants: A Novel Autosomal Recessive Cardiac Syndrome🧬 In this episode of Base by Base, we discuss a groundbreaking study by Nicastro et al. (2025) published in The American Journal of Human Genetics, which identifies bi-allelic loss-of-function variants in the POPDC2 gene as the cause of a previously unrecognized autosomal recessive syndrome characterized by cardiac conduction defects and hypertrophic cardiomyopathy. The authors sequenced affected individuals and

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00:18:31

️ 36: Bi-allelic POPDC2 Variants: A Novel Autosomal...

Base by Base ·

2025/06/06

️ Episode 36: Bi-allelic POPDC2 Variants: A Novel Autosomal Recessive Cardiac Syndrome In this episode of Base by Base, we discuss a groundbreaking study by Nicastro et al. (2025) published in The American Journal of Human Genetics, which identifies bi-allelic loss-of-function variants in the POPDC2 gene as the cause of a previously unrecognized autosomal recessive syndrome characterized by cardiac conduction defects and hypertrophic cardiomyopathy. The

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00:18:19

🎙️ 35: Tracing the Evolutionary History of CCR5Δ32 —...

Base by Base ·

2025/06/06

🎙️ Episode 35: Tracing the Evolutionary History of CCR5Δ32 — Insights from Ancient and Modern Genomes🧬 In this episode of Base by Base, we explore groundbreaking research by Ravn et al. (2025) published in Cell that reconstructs the origin, spread, and selective pressures acting on the CCR5Δ32 deletion in human populations. Through a comprehensive analysis of 934 ancient genomes and 2,504 present-day genomes, the authors trace how this 32-base-pair deletion in the CCR5 gene—known to confer

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00:18:20

️ 35: Tracing the Evolutionary History of CCR5Δ32 —...

Base by Base ·

2025/06/06

️ Episode 35: Tracing the Evolutionary History of CCR5Δ32 — Insights from Ancient and Modern Genomes In this episode of Base by Base, we explore groundbreaking research by Ravn et al. (2025) published in Cell that reconstructs the origin, spread, and selective pressures acting on the CCR5Δ32 deletion in human populations. Through a comprehensive analysis of 934 ancient genomes and 2,504 present-day genomes, the authors trace how this 32-base-pair deletion

en-us

00:22:50

🎙️ 34: Enzyme Replacement Therapy in Homocystinuria —...

Base by Base ·

2025/06/06

🎙️ Episode 34: Enzyme Replacement Therapy in Homocystinuria — Safety and Efficacy of Pegtibatinase in the Phase 1/2 COMPOSE Trial🧬 In this episode of Base by Base, we delve into early findings from Ficicioglu et al. (2025) published in Genetics in Medicine, which evaluate pegtibatinase, a PEGylated truncated human cystathionine β-synthase enzyme replacement, in adults with classical homocystinuria (HCU). The COMPOSE Phase 1/2 trial randomized individuals with elevated total plasma homocysteine

en-us

00:22:51

️ 34: Enzyme Replacement Therapy in Homocystinuria —...

Base by Base ·

2025/06/06

️ Episode 34: Enzyme Replacement Therapy in Homocystinuria — Safety and Efficacy of Pegtibatinase in the Phase 1/2 COMPOSE Trial In this episode of Base by Base, we delve into early findings from Ficicioglu et al. (2025) published in Genetics in Medicine, which evaluate pegtibatinase, a PEGylated truncated human cystathionine β-synthase enzyme replacement, in adults with classical homocystinuria (HCU). The COMPOSE Phase 1/2 trial randomized individuals

en-us

00:20:35

🎙️ 33: Mis-splicing-derived Neoantigens — A New...

Base by Base ·

2025/06/05

🎙️ Episode 33: Mis-splicing-derived Neoantigens — A New Avenue for Immunotherapy in Leukemia🧬 In this episode of Base por Base, we examine groundbreaking research by Kim et al. (2025), recently published in Cell, that uncovers a promising immunotherapeutic strategy targeting leukemia-associated splicing factor mutations. The study identifies recurrent neoantigens arising from mis-splicing events in SRSF2 and ZRSR2 mutant myeloid leukemias, which can be exploited for T cell receptor (TCR)-based

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465 results

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