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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

00:15:11

197: Somatic Mutation and Selection at Population Scale

Base by Base ·

2025/11/13

️ Episode 197: Somatic Mutation and Selection at Population Scale In this episode of PaperCast Base by Base, we explore how ultra-accurate NanoSeq duplex sequencing reveals the hidden landscape of somatic mutations and clonal selection across blood and oral epithelium in over a thousand adults. Study Highlights:This study introduces improved whole-genome and targeted versions of NanoSeq, a duplex sequencing method with error rates below five mutations

en-us

00:16:37

196: Impact of Chromatin Accessibility QTLs Across...

Base by Base ·

2025/11/12

️ 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:The authors harmonized ∼280,000 PBMC scATAC-seq profiles from 48 individuals—including healthy donors and

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00:18:22

195: Tiny Shields: Lymphoid Microglia in Alzheimer’s...

Base by Base ·

2025/11/11

️ 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 Alzheimer’s brain tissue, the authors identify plaque-associated microglia with reduced PU.1 expression

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00:14:29

194: Bayesian History of Science: Watson and Crick...

Base by Base ·

2025/11/10

️ 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 evolving evidence that supported or undermined each hypothesis. Study Highlights:The author applies a naïve

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00:15:00

193: SARM1, DNA, and the Death Signal

Base by Base ·

2025/11/09

️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 the immune adaptor SARM1 directly binds double-stranded DNA via its TIR domain and, once activated, rapidly

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00:14:24

192: At Base-Pair Resolution: Chromatin’s...

Base by Base ·

2025/11/08

️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 Micro Capture-C ultra (MCCu), the authors generate multidimensional chromosome conformation maps with single

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00:19:17

191: CATphishing: Synthetic Learning as an...

Base by Base ·

2025/11/07

️ 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 data. The work spans seven institutions and 2,491 patients and evaluates whether models trained on synthetic

en-us

00:19:17

191: CATphishing: Synthetic Learning as an...

Base by Base ·

2025/11/07

️ 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 data. The work spans seven institutions and 2,491 patients and evaluates whether models trained on synthetic

en-us

00:15:43

190: Single-Cell Networks Reveal Cell Type–Specific...

Base by Base ·

2025/11/06

️ 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 Highlights:The authors develop differential Gene Coordination Network Analysis (dGCNA) to compare gene–gene

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00:14:22

189: DNA methylation patterns facilitate tracing the...

Base by Base ·

2025/11/05

️ 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 NEN”. Study Highlights:Using two independent cohorts totaling 212 NEN tissues, the authors profiled

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00:16:51

188: Proteomics + Machine Learning for Lyme...

Base by Base ·

2025/11/04

️ 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. Study Highlights:The authors analyzed 308 CSF and 207 plasma samples across development and validation

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00:16:13

187: Gapped PARP + Tumor‑Targeted TOP1 in Advanced...

Base by Base ·

2025/11/03

️ 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 efficacy in advanced solid tumors. Study Highlights:Twenty‑four adults with advanced solid tumors received

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00:15:22

186: TNFα–TGFβ Axis Disrupts Nasal Epithelium in...

Base by Base ·

2025/11/02

️ 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 Highlights:Researchers profiled >56,000 cells from nasal tissue of individuals with moderate or severe

en-us

00:14:59

185: Altered Milk Tryptophan in Women Living with HIV

Base by Base ·

2025/11/01

️ 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:The authors profiled the milk metabolome from hundreds of mothers over the first 18 months postpartum and

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00:17:44

184: High-Accuracy Multiethnic XGBoost for Skin...

Base by Base ·

2025/10/31

️ 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 participants, the authors quantify independent associations between genetic ancestry, lifestyle, social

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00:17:44

184: High-Accuracy Multiethnic XGBoost for Skin...

Base by Base ·

2025/10/31

️ 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 participants, the authors quantify independent associations between genetic ancestry, lifestyle, social

en-us

00:18:05

183: The Genetic Lottery Goes to School: Better...

Base by Base ·

2025/10/30

️ 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, and Child Cohort (MoBa) and nationwide administrative data, the authors combine within-family polygenic

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00:16:18

182: Genotypic, Functional, and Phenotypic...

Base by Base ·

2025/10/29

️ 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 analyze variant types across 127 individuals from 20 countries, probe Wnt/β-catenin signaling consequences in

en-us

00:12:44

181: Creatine Transporter SLC6A8: Conservation and...

Base by Base ·

2025/10/28

️ 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 relationships in creatine transporter deficiency. fileciteturn0file0 Study Highlights:The authors compared CRT1

en-us

00:22:11

180: Leveraging Global Genetics Resources for...

Base by Base ·

2025/10/27

️ 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 practical, computationally efficient strategies that work even when individual-level data are unavailable. Study

en-us

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