Estimating the dynamics and dependencies of accumulating mutations with applications to HIV drug resistance.
Biostatistics
; 16(4): 713-26, 2015 Oct.
Article
en En
| MEDLINE
| ID: mdl-25979750
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Modelos Estadísticos
/
VIH
/
Farmacorresistencia Viral
/
Acumulación de Mutaciones
/
Modelos Genéticos
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Biostatistics
Año:
2015
Tipo del documento:
Article
País de afiliación:
Suiza
Pais de publicación:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM