Estimating the dynamics and dependencies of accumulating mutations with applications to HIV drug resistance
Montazeri, Hesam ; Montazeri, Hesam ; Günthard, Huldrych F. ; Yang, Wan-Lin ; Kouyos, Roger ; Beerenwinkel, Niko ; Montazeri, Hesam ; Günthard, Huldrych F. ; Yang, Wan-Lin ; Kouyos, Roger ; Beerenwinkel, Niko
In: Biostatistics, 2015, vol. 16, no. 4, p. 713-726
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- We introduce a new model called the observed time conjunctive Bayesian network (OT-CBN) that describes the accumulation of genetic events (mutations) under partial temporal ordering constraints. Unlike other CBN models, the OT-CBN model uses sampling time points of genotypes in addition to genotypes themselves to estimate model parameters. We developed an expectation-maximization algorithm to obtain approximate maximum likelihood estimates by accounting for this additional information. In a simulation study, we show that the OT-CBN model outperforms the continuous time CBN (CT-CBN) (Beerenwinkel and Sullivant, 2009. Markov models for accumulating mutations. Biometrika 96(3), 645-661), which does not take into account individual sampling times for parameter estimation. We also show superiority of the OT-CBN model on several datasets of HIV drug resistance mutations extracted from the Swiss HIV Cohort Study database