Base by Base

️ 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 2...

Nature Communications (2025) 16:9457 et al., Nature Communications - Phase I dose-escalation trial combining CRLX101 (nanoparticle camptothecin) with olaparib using a 48-hour gapped schedule in 24 patients with advanced solid tumors to determine MTD and assess pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy. Key terms: CRLX101, olaparib, PARP inhibitor, topoisomerase I, gapped...

️ 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...

️ 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 hu...

️ 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 asso...

️ 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 administra...

️ 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 c...

️ 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tu...

️ 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...

️ 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 postnatal diagnoses to clarify how maternal age and repro...

️ 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 penetrance relative to classic Li-Fraumeni syndrome. St...

️ 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 long‑recognized association with hypogonadism. Study...

️ 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 FAHD1 as a central regulator linked to poor prognos...

️ 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 framewo...

️ 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 autho...

️ 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...

️ 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 scr...

Danchuk S et al., Proceedings of the National Academy of Sciences - Virulence Hierarchies in the Tuberculosis Complex—What Makes Some Lineages Deadlier? Music: Enjoy the music based on this article at the end of the episode. Article title: Virulence hierarchies within the Mycobacterium tuberculosis complex First author: Danchuk S Journal: Proceedings of the National Academy of Sciences DOI: 10.107...

Picchetta L et al., The American Journal of Human Genetics - Maternal Age, Meiotic Recombination Failure, and Triploidy in Humans Music: Enjoy the music based on this article at the end of the episode. Article title: Maternal age and genome-wide failure of meiotic recombination are associated with triploid conceptions in humans First author: Picchetta L Journal: The American Journal of Human Genet...

Aslanzadeh V et al., Nature Communications - Deep mutational scanning of the insulin receptor guides precision therapy for insulin resistance Music: Enjoy the music based on this article at the end of the episode. Article title: Deep mutational scanning of the human insulin receptor ectodomain to inform precision therapy for insulin resistance First author: Aslanzadeh V Journal: Nature Communicati...

Baird D et al., Nature Communications - Low circulating miR-190a-5p predicts progression of chronic kidney disease Music: Enjoy the music based on this article at the end of the episode. Article title: Low circulating miR-190a-5p predicts progression of chronic kidney disease First author: Baird D Journal: Nature Communications DOI: 10.1038/s41467-025-64168-6 Reference: Baird D.P., Zang J., Connor...

Qu Y et al., Cell Genomics - DeepScence: Detecting Senescent Cells at Single-Cell and Spatial Resolution Music: Enjoy the music based on this article at the end of the episode. Article title: Single-cell and spatial detection of senescent cells using DeepScence First author: Qu Y Journal: Cell Genomics DOI: 10.1016/j.xgen.2025.101035 Reference: Qu Y., Ji B., Dong R., Gu L., Chan C., Xie J., et al....

Oosterheert W et al., Cell - Molecular Squeezing: How Coronin, Cofilin, and AIP1 Rapidly Disassemble Actin Filaments Music: Enjoy the music based on this article at the end of the episode. Article title: Choreography of rapid actin filament disassembly by coronin, cofilin, and AIP1 First author: Oosterheert W Journal: Cell DOI: 10.1016/j.cell.2025.09.016 Reference: Oosterheert W., Boiero Sanders M...

Schoenle A et al., Trends in Genetics - Protist Genomics: Key to Understanding Eukaryotic Evolution Music: Enjoy the music based on this article at the end of the episode. Article title: Protist genomics: key to understanding eukaryotic evolution First author: Schoenle A Journal: Trends in Genetics DOI: 10.1016/j.tig.2025.05.004 Reference: Schoenle A., Francis O., Archibald J.M., Burki F., de Vrie...

Ćorović M et al., Trends in Genetics - m6A in the coding sequence: linking deposition, translation, and decay Music: Enjoy the music based on this article at the end of the episode. Article title: m6A in the coding sequence: linking deposition, translation, and decay First author: Ćorović M Journal: Trends in Genetics DOI: 10.1016/j.tig.2025.06.002 Reference: Ćorović M., Hoch-Kraft P., Zhou Y., Ha...