Timing copy number alterations in Barrett’s Oesophagus using hierarchical Bayesian models

Abstract: The accumulation of somatic copy number alterations (CNAs) is a key genomic risk factor in the progression from Barrett’s Oesophagus (a pre-malignant condition, BO) to oesophageal adenocarcinoma (OAC). However, the timing and evolutionary dynamics of these CNAs have remained elusive. In this talk, I will introduce CARBINE (Copy number AlteRation timing with Bayesian Inference and Neutral Evolution), a hierarchical Bayesian framework designed to infer the calendar-time occurrence of CNAs from deep whole-genome sequencing data. CARBINE leverages molecular clock signals and clonal evolutionary theory to estimate patient-specific mutation rates, clonal growth dynamics, and the timing of genomic events from single-timepoint samples. Using this method, we find that critical alterations, such as whole-genome doubling and TP53 inactivation, often occur decades before cancer diagnosis, including during early life, and are followed by long periods of indolent clonal expansion. Furthermore, we show that the rate of CNA accumulation—estimated from single snapshots—outperforms overall burden as a predictor of progression to OAC. This new insight into the temporal evolution of BO underscores the potential of early-life genomic profiling to stratify cancer risk and informs strategies for early intervention.

machine learningprobabilitystatistics theory

Audience: researchers in the discipline

Gothenburg statistics seminar

Series comments: Gothenburg statistics seminar is open to the interested public, everybody is welcome. It usually takes place in MVL14 (http://maps.chalmers.se/#05137ad7-4d34-45e2-9d14-7f970517e2b60, see specific talk). Speakers are asked to prepare material for 35 minutes excluding questions from the audience.