Material Detail

This video was recorded at 6th International Workshop on Machine Learning in Systems Biology (MLSB), Basel 2012. Motivation: Cancer development is driven by the accumulation of advantageous mutations and subsequent clonal expansion of cells harbouring these mutations, but the order in which mutations occur remains poorly understood. Advances in genome sequencing and the soon-arriving flood of cancer genome data produced by large cancer sequencing consortia hold the promise to elucidate cancer progression. However, new computational methods are needed to analyse these large datasets. Results: We present a Bayesian inference scheme for Conjunctive Bayesian Networks, a probabilistic graphical model in which mutations accumulate according to partial order constraints and cancer genotypes are observed subject to measurement noise. We develop an efficient MCMC sampling scheme specifically designed to overcome local optima induced by dependency structures. We demonstrate the performance advantage of our sampler over traditional approaches on simulated data and show the advantages of adopting a Bayesian perspective when reanalysing cancer datasets and comparing our results to previous maximum likelihood-based approaches. Availability: An R package including the sampler and examples is available at http://www.cbg.ethz.ch/software/bayes-cbn

Disciplines:

• Science and Technology  / Biology  / Genetics

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