Efficient sampling for Bayesian inference of conjunctive Bayesian networks.
BACKGROUND
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 reanalyzing cancer datasets and comparing our results to previous maximum-likelihood-based approaches.


BACKGROUND
An R package including the sampler and examples is available at http://www.cbg.ethz.ch/software/bayes-cbn.


BACKGROUND
niko.beerenwinkel@bsse.ethz.ch.
Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland.
Thomas
T
Sakoparnig
Niko
N
Beerenwinkel
D000465:Algorithms; D001499:Bayes Theorem; D023281:Genomics; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D015233:Models, Statistical; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*