Header

UZH-Logo

Maintenance Infos

Estimating the dynamics and dependencies of accumulating mutations with applications to HIV drug resistance


Montazeri, Hesam; Günthard, Huldrych F; Yang, Wan-Lin; Kouyos, Roger; Beerenwinkel, Niko (2015). Estimating the dynamics and dependencies of accumulating mutations with applications to HIV drug resistance. Biostatistics, 16(4):713-726.

Abstract

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.

Abstract

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.

Statistics

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Virology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:October 2015
Deposited On:01 Feb 2016 08:54
Last Modified:05 Apr 2016 20:05
Publisher:Oxford University Press
ISSN:1465-4644
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/biostatistics/kxv019
PubMed ID:25979750

Download

Full text not available from this repository.
View at publisher