201: Sex, Smoking, and Somatic Selection in the Bladder

Music:Enjoy the music based on this article at the end of the episode. DOI:10.1038/s41586-025-09521-x License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. ️ Episode:201: 201: Sex, Smoking, and Somatic Selection in the Bladder ️ Season:1 Article title:Sex and smoking bias in the selection of somatic mutations in human bladder Journal:Nature QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-11-17. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Substantively audited transcript sections describing the sequencing approach, gene panel, positive/negative selection signals, TERT promoter mutations linked to age and smoking, smoking as promoter, FGFR3 negative selection, natural saturation mutagenesis, TP53 site selection, sex differences, and sampling design (dome- transcript topics: Ultradeep duplex sequencing of normal urothelium; Driver mutations in RBM10, CDKN1A, ARID1A; Positive/negative selection signals (dN/dS, clustering, functional bias); TERT promoter activating mutations and association with age and smoking; Smoking as promoter rather than global mutagenesis; FGFR3 truncating mutations under negative selection QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 8- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi- article_title- article_journal- license Factual Items Audited:- Ultradeep sequencing identified thousands of driver mutations across 16 genes in normal urothelium- Men show higher truncating driver mutations in RBM10, CDKN1A, ARID1A than women- Activating TERT promoter mutations detected in normal bladder tissue and associated with age and smoking- TERT promoter mutations promote clonal expansions rather than globally increasing mutation density in smokers- FGFR3 truncating mutations exhibit negative selection in normal urothelium- Natural saturation mutagenesis observed in vivo via ultradeep sequencing, with TP53 site-specific positive selection QC result: Pass.