BEGIN:VCALENDAR VERSION:2.0 PRODID:researchseminars.org CALSCALE:GREGORIAN X-WR-CALNAME:researchseminars.org BEGIN:VEVENT SUMMARY:Calum Gabbutt (Imperial College London) DTSTART:20250507T111500Z DTEND:20250507T120000Z DTSTAMP:20260422T155330Z UID:gbgstats/81 DESCRIPTION:Title: Timing copy number alterations in Barrett’s Oesophagus using hierarchi cal Bayesian models\nby Calum Gabbutt (Imperial College London) as par t of Gothenburg statistics seminar\n\nLecture held in MVL14.\n\nAbstract\n The accumulation of somatic copy number alterations (CNAs) is a key genomi c risk factor in the progression from Barrett’s Oesophagus (a pre-malign ant condition\, BO) to oesophageal adenocarcinoma (OAC). However\, the tim ing and evolutionary dynamics of these CNAs have remained elusive. In this talk\, I will introduce CARBINE (Copy number AlteRation timing with Bayes ian Inference and Neutral Evolution)\, a hierarchical Bayesian framework d esigned to infer the calendar-time occurrence of CNAs from deep whole-geno me sequencing data. CARBINE leverages molecular clock signals and clonal e volutionary theory to estimate patient-specific mutation rates\, clonal gr owth dynamics\, and the timing of genomic events from single-timepoint sam ples. Using this method\, we find that critical alterations\, such as whol e-genome doubling and TP53 inactivation\, often occur decades before cance r diagnosis\, including during early life\, and are followed by long perio ds of indolent clonal expansion. Furthermore\, we show that the rate of CN A accumulation—estimated from single snapshots—outperforms overall bur den as a predictor of progression to OAC. This new insight into the tempor al evolution of BO underscores the potential of early-life genomic profili ng to stratify cancer risk and informs strategies for early intervention.\ n LOCATION:https://researchseminars.org/talk/gbgstats/81/ END:VEVENT END:VCALENDAR