Best basebybase.podcast@gmail.com (Gustavo Barra Podcasts (2025)

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196: Impact of Chromatin Accessibility QTLs Across Immune Contexts 16:37

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9h ago16:37

16:37

️ Episode 196: Impact of Chromatin Accessibility QTLs Across Immune Contexts In this episode of PaperCast Base by Base, we explore how single-cell chromatin accessibility QTLs (caQTLs) reshape the interpretation of immune disease genetics by mapping regulatory variation across major immune cell types and disease-relevant states. Study Highlights: T…

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195: Tiny Shields: Lymphoid Microglia in Alzheimer’s Disease 18:22

1d ago18:22

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️ Episode 195: Tiny Shields: Lymphoid Microglia in Alzheimer’s Disease In this episode of PaperCast Base by Base, we explore how a subset of brain immune cells adopts a lymphoid-like program that helps contain inflammation and protect neural circuits in Alzheimer’s disease models. Study Highlights: Using mouse models of amyloid pathology and human …

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194: Bayesian History of Science: Watson and Crick and the Structure of DNA 14:29

2d ago14:29

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️ Episode 194: Bayesian History of Science: Watson and Crick and the Structure of DNA In this episode of PaperCast Base by Base, we explore how Bayesian reasoning can be used to reconstruct the famous discovery of the DNA double helix by James Watson and Francis Crick, following the sequence of structural models proposed in the early 1950s and the …

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193: SARM1, DNA, and the Death Signal 15:00

3d ago15:00

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️Episode 193: SARM1, DNA, and the Death Signal In this episode of PaperCast Base by Base, we explore how the axon-degenerating enzyme SARM1 acts as a double-stranded DNA sensor that triggers NAD+ loss, cell death, and chemotherapy-induced neuropathy, opening up new possibilities for neuroprotective therapies. Study Highlights: The authors show that…

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192: At Base-Pair Resolution: Chromatin’s Cis-Regulatory Conversations 14:24

4d ago14:24

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️Episode 192: At Base-Pair Resolution: Chromatin’s Cis-Regulatory Conversations In this episode of PaperCast Base by Base, we explore how base-pair resolution maps of chromatin contacts reveal a unified, biophysical model of communication between enhancers, promoters, and other cis-regulatory elements in mammalian cells. Study Highlights: Using Mic…

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191: CATphishing: Synthetic Learning as an Alternative to Federated Learning in MRI 19:17

5d ago19:17

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️ Episode 191: CATphishing: Synthetic Learning as an Alternative to Federated Learning in MRI In this episode of PaperCast Base by Base, we explore a Nature Communications study that proposes CATphishing—an approach that uses latent diffusion models to generate site-specific synthetic 3D brain MRIs for collaborative training without sharing raw dat…

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190: Single-Cell Networks Reveal Cell Type–Specific Mechanisms in Type 2 Diabetes 15:43

6d ago15:43

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️ Episode 190: Single-Cell Networks Reveal Cell Type–Specific Mechanisms in Type 2 Diabetes In this episode of PaperCast Base by Base, we explore how a network-based analysis of single-cell RNA sequencing from human pancreatic islets uncovers cell type–specific gene-regulatory changes that help explain type 2 diabetes pathophysiology. Study Highlig…

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189: DNA methylation patterns facilitate tracing the origin of neuroendocrine neoplasms 14:22

7d ago14:22

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️ Episode 189: DNA methylation patterns facilitate tracing the origin of neuroendocrine neoplasms In this episode of PaperCast Base by Base, we explore how genome-wide DNA methylation profiling can pinpoint the organ of origin for neuroendocrine neoplasms (NEN), with a special focus on lesions detected in the liver and long-debated “primary hepatic…

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188: Proteomics + Machine Learning for Lyme Neuroborreliosis Diagnosis 16:51

8d ago16:51

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️ Episode 188: Proteomics + Machine Learning for Lyme Neuroborreliosis Diagnosis In this episode of PaperCast Base by Base, we explore how large‑scale mass‑spectrometry proteomics of cerebrospinal fluid and plasma, paired with supervised machine learning, can distinguish Lyme neuroborreliosis from viral meningitis and non‑LNB controls in adults. St…

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187: Gapped PARP + Tumor‑Targeted TOP1 in Advanced Tumors 16:13

9d ago16:13

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️ Episode 187: Gapped PARP + Tumor‑Targeted TOP1 in Advanced Tumors In this episode of PaperCast Base by Base, we explore a phase I dose‑escalation trial that pairs a tumor‑targeted topoisomerase I inhibitor (CRLX101, a nanoparticle camptothecin) with optimized, gapped scheduling of the PARP inhibitor olaparib to reduce toxicity while preserving ef…

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186: TNFα–TGFβ Axis Disrupts Nasal Epithelium in Post‑COVID Syndrome 15:22

10d ago15:22

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️ Episode 186: TNFα–TGFβ Axis Disrupts Nasal Epithelium in Post‑COVID Syndrome In this episode of PaperCast Base by Base, we explore a single‑cell RNA‑seq study of nasal biopsies showing that persistent immune signaling—not residual virus—drives aberrant epithelial differentiation in people with post‑COVID syndrome. fileciteturn1file0 Study High…

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185: Altered Milk Tryptophan in Women Living with HIV 14:59

11d ago14:59

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️ Episode 185: Altered Milk Tryptophan in Women Living with HIV In this episode of PaperCast Base by Base, we explore a longitudinal metabolomics study of human milk that reveals how maternal HIV infection reshapes tryptophan metabolism across lactation, with potential implications for infant immunity, growth, and neurodevelopment. Study Highlights…

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184: High-Accuracy Multiethnic XGBoost for Skin Cancer Identification 17:44

12d ago17:44

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️ Episode 184: High-Accuracy Multiethnic XGBoost for Skin Cancer Identification In this episode of PaperCast Base by Base, we explore a large-scale study that builds a risk factor–based XGBoost model using the All of Us cohort to accurately identify patients with skin cancer across diverse ancestries. Study Highlights: Analyzing more than 400,000 p…

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183: The Genetic Lottery Goes to School: Better Schools Compensate for Genetic Differences 18:05

13d ago18:05

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️ Episode 183: The Genetic Lottery Goes to School: Better Schools Compensate for Genetic Differences In this episode of PaperCast Base by Base, we explore a large causal study from Norway asking whether school quality can offset genetic differences in students’ academic skills. Using parent–offspring genetic trios from the Norwegian Mother, Father,…

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182: Genotypic, Functional, and Phenotypic Characterization in CTNNB1 Neurodevelopmental Syndrome 16:18

14d ago16:18

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️ Episode 182: Genotypic, Functional, and Phenotypic Characterization in CTNNB1 Neurodevelopmental Syndrome In this episode of PaperCast Base by Base, we explore a large cross-sectional cohort study that integrates genetics, cellular functional assays, and deep phenotyping to map the landscape of CTNNB1 neurodevelopmental syndrome. The authors anal…

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181: Creatine Transporter SLC6A8: Conservation and Variant Impact 12:44

15d ago12:44

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️ Episode 181: Creatine Transporter SLC6A8: Conservation and Variant Impact In this episode of PaperCast Base by Base, we explore how the creatine transporter gene SLC6A8 (CRT1) is evolutionarily conserved across terrestrial mammals and how disease-associated variants alter creatine uptake in vitro, shedding light on genotype–phenotype relationship…

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180: Leveraging Global Genetics Resources for Equitable Polygenic Prediction 22:11

16d ago22:11

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️ Episode 180: Leveraging Global Genetics Resources for Equitable Polygenic Prediction In this episode of PaperCast Base by Base, we explore how multi-ancestry genome-wide association study resources and modern polygenic score methodologies can improve prediction accuracy across African, East Asian, and European populations, with a focus on practic…

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179: Mosaicism for Autosomal Trisomies: Maternal Age, UPD, and Reproductive History in 1,266 Cases 16:49

17d ago16:49

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️ Episode 179: Mosaicism for Autosomal Trisomies: Maternal Age, UPD, and Reproductive History in 1,266 Cases In this episode of PaperCast Base by Base, we explore a comprehensive literature analysis of 1,266 reported cases of autosomal trisomy mosaicism, contrasting prenatal cohorts—true fetal mosaicism and confined placental mosaicism—with postnat…

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178: TP53 Reduced Penetrance: Predictive Features and Clinical Implications 15:59

18d ago15:59

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️ Episode 178: TP53 Reduced Penetrance: Predictive Features and Clinical Implications In this episode of PaperCast Base by Base, we explore how a large ClinVar-anchored analysis integrates functional assays, computational predictors, immunogenicity estimates, allele frequencies, and clinical presentation to identify TP53 variants with reduced penet…

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177: Biallelic MCM8/MCM9 Variants: From Hypogonadism to Cancer Predisposition 17:04

19d ago17:04

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️ Episode 177: Biallelic MCM8/MCM9 Variants: From Hypogonadism to Cancer Predisposition In this episode of PaperCast Base by Base, we explore a multi‑cohort clinical–genomic study that delineates the phenotype of individuals with biallelic germline variants in MCM8 or MCM9, clarifying links to polyposis and early‑onset cancers in addition to the lo…

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176: FAHD1 and the Pyruvate-Driven Evolution of Hepatocellular Carcinoma 19:32

20d ago19:32

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️ Episode 176: FAHD1 and the Pyruvate-Driven Evolution of Hepatocellular Carcinoma In this episode of PaperCast Base by Base, we explore how multi-omics integration—spanning single-cell transcriptomics, spatial mapping, and causal genetic inference—uncovers a pyruvate-hyperactive epithelial subpopulation in hepatocellular carcinoma and identifies F…

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175: Predictive Prioritization of Pancreatic Enhancers Linked to Disease Risk 19:13

21d ago19:13

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️ 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…

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174: TMEM217–SLC9C1: Wiring the cAMP Switch for Sperm Motility and Male Fertility 16:40

22d ago16:40

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️ 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 p…

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173: Bottlebrush Block Copolymer Shields Muscles and Prevents DMD Onset 20:12

23d ago20:12

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️ 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 engine…

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172: When Random DNA Fights Back: De Novo Gene Birth as Antiphage Defense 19:44

24d ago19:44

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️ 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. file…

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171: Virulence Hierarchies in the Tuberculosis Complex—What Makes Some Lineages Deadlier? 16:14

25d ago16:14

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️ 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 de…

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170: Maternal Age, Meiotic Recombination Failure, and Triploidy in Humans 17:03

26d ago17:03

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️ 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 Highlig…

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169: Deep mutational scanning of the insulin receptor guides precision therapy for insulin resistance 21:13

27d ago21:13

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️ 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 s…

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168: Low circulating miR-190a-5p predicts progression of chronic kidney disease 19:10

28d ago19:10

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️ 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 therape…

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167: DeepScence: Detecting Senescent Cells at Single-Cell and Spatial Resolution 21:40

29d ago21:40

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️ 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, out…

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166: Molecular Squeezing: How Coronin, Cofilin, and AIP1 Rapidly Disassemble Actin Filaments 13:37

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️ 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. Stud…

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165: Protist Genomics: Key to Understanding Eukaryotic Evolution 19:24

1M ago19:24

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️ 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 methodol…

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164: m6A in the coding sequence: linking deposition, translation, and decay 14:46

1M ago14:46

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️ 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 acros…

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163: Animal origins: looping back in time 14:18

1M ago14:18

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️ 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–pr…

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162: Spatially Resolved microRNA Expression in Tissues: Technologies, Challenges, and Opportunities 20:15

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️ 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 as…

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161: Decoding Genomic Landscapes of Introgression 20:55

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️ 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 g…

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160: The Long‑Read Leap in Single‑Cell Omics 15:36

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By Gustavo Barra

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159: The Untapped Potential of Short‑Read Sequencing in Biodiversity Research 15:56

1M ago15:56

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️ 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 c…

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158: Interruptions in Repeat Expansion Diseases: How Are They Gained and Lost? 22:35

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️ Episode 158: Interruptions in Repeat Expansion Diseases: How Are They Gained and Lost? 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 …

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157: Synthetic gametes and the non-identity problem: the babies of tomorrow 14:32

1M ago14:32

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️ Episode 157: Synthetic gametes and the non-identity problem: the babies of tomorrow In this episode of PaperCast Base by Base, we explore how synthetic DNA technologies may enable the creation of synthetic gametes and why this possibility forces a rethinking of identity, harm, and responsibility in human reproduction. Study Highlights: The author…

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156: RAEFISH: Sequencing-free whole-genome spatial transcriptomics at single-molecule resolution 17:07

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️ Episode 156: RAEFISH: Sequencing-free whole-genome spatial transcriptomics at single-molecule resolution In this episode of PaperCast Base by Base, we explore RAEFISH, a reverse-padlock amplicon-encoding FISH method that delivers whole-transcriptome imaging at single-molecule resolution without sequencing. The study demonstrates genome-scale cove…

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155: EIF3A/EIF3B Loss-of-Function: A Cardiocraniofacial Neurodevelopmental Syndrome 15:53

1M ago15:53

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️ Episode 155: EIF3A/EIF3B Loss-of-Function: A Cardiocraniofacial Neurodevelopmental Syndrome In this episode of PaperCast Base by Base, we explore how loss-of-function variants in EIF3A and EIF3B—core components of the eIF3 translation initiation complex—cause a multisystem disorder marked by congenital heart defects, craniofacial differences, and…

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154: Multiple-testing corrections in selection scans using identity-by-descent segments 20:05

1M ago20:05

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️ Episode 154: Multiple-testing corrections in selection scans using identity-by-descent segments In this episode of PaperCast Base by Base, we explore how Temple and Browning develop principled genome-wide significance thresholds for IBD-based scans of recent positive selection by explicitly modeling correlation along the genome. Study Highlights:…

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153: Skeletal muscle eQTL meta-analysis implicates genes in the genetic architecture of muscular and cardiometabolic traits 15:13

1M ago15:13

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️ Episode 153: Skeletal muscle eQTL meta-analysis implicates genes in the genetic architecture of muscular and cardiometabolic traits In this episode of PaperCast Base by Base, we explore a large skeletal muscle eQTL meta-analysis that integrates GTEx and FUSION data to pinpoint regulatory variants and genes underlying muscular and cardiometabolic …

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152: One-Well Multiplex ddPCR for Hereditary Alpha Tryptasemia 16:53

1M ago16:53

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️ Episode 152: One-Well Multiplex ddPCR for Hereditary Alpha Tryptasemia In this episode of PaperCast Base by Base, we explore a validated single‑well multiplex digital droplet PCR (ddPCR) assay that reconstructs the TPSAB1 locus by quantifying α‑ and β‑tryptase copy numbers to diagnose hereditary alpha tryptasemia (HαT) in symptomatic patients. St…

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151: EQA of ctDNA Mutation Testing Across the COIN Consortium 16:21

2M ago16:21

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️ Episode 151: EQA of ctDNA Mutation Testing Across the COIN Consortium In this episode of PaperCast Base by Base, we explore how 16 Dutch laboratories evaluated their real‑world workflows for circulating tumor DNA (ctDNA) mutation testing across BRAF, EGFR, and KRAS using a coordinated external quality assessment within the COIN consortium. Study …

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150: Patrilineal segmentary systems and the post‑Neolithic Y‑chromosome bottleneck 17:52

2M ago17:52

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️ Episode 150: Patrilineal segmentary systems and the post‑Neolithic Y‑chromosome bottleneck In this episode of PaperCast Base by Base, we explore a Nature Communications study that proposes a peaceful, socio‑cultural explanation for the sharp decline in male effective population size observed 3,000–5,000 years ago. Instead of widespread violence, …

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149: Cultural Hitchhiking and the Post‑Neolithic Y‑Chromosome Bottleneck 15:04

2M ago15:04

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️ Episode 149: Cultural Hitchhiking and the Post‑Neolithic Y‑Chromosome Bottleneck In this episode of PaperCast Base by Base, we explore how patrilineal social structures and intergroup competition can reshape genetic diversity, offering a cultural explanation for the striking male‑specific bottleneck observed 5,000–7,000 years ago across the Old W…

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148: Systematic Minigene-Based Splicing Analysis and Tentative Clinical Classification of 52 CHEK2 Splice-Site Variants 14:44

2M ago14:44

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️ Episode 148: Systematic Minigene-Based Splicing Analysis and Tentative Clinical Classification of 52 CHEK2 Splice-Site Variants In this episode of PaperCast Base by Base, we explore a comprehensive functional assessment of splice-site variants in CHEK2 using reporter minigenes, revealing how disrupted pre-mRNA splicing contributes to hereditary b…

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147: Comprehensive Annotation of Complete ABO Alleles and Resolution of ABO Variants 15:37

2M ago15:37

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️ Episode 147: Comprehensive Annotation of Complete ABO Alleles and Resolution of ABO Variants In this episode of PaperCast Base by Base, we explore a groundbreaking study that introduces an improved long-read sequencing method to fully resolve ABO haplotypes, spanning from the 5′ to the 3′ untranslated regions. This work addresses a major gap in b…

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