Dataset Information

Maximum-Likelihood Tree Estimation Using Codon Substitution Models with Multiple Partitions.

ABSTRACT: Many protein sequences have distinct domains that evolve with different rates, different selective pressures, or may differ in codon bias. Instead of modeling these differences by more and more complex models of molecular evolution, we present a multipartition approach that allows maximum-likelihood phylogeny inference using different codon models at predefined partitions in the data. Partition models can, but do not have to, share free parameters in the estimation process. We test this approach with simulated data as well as in a phylogenetic study of the origin of the leucin-rich repeat regions in the type III effector proteins of the pythopathogenic bacteria Ralstonia solanacearum. Our study does not only show that a simple two-partition model resolves the phylogeny better than a one-partition model but also gives more evidence supporting the hypothesis of lateral gene transfer events between the bacterial pathogens and its eukaryotic hosts.

SUBMITTER: Zoller S

PROVIDER: S-EPMC4833081 | biostudies-other | 2015 Aug

REPOSITORIES: biostudies-other

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Maximum-Likelihood Tree Estimation Using Codon Substitution Models with Multiple Partitions.

Zoller Stefan S Boskova Veronika V Anisimova Maria M

Molecular biology and evolution 20150423 8

Many protein sequences have distinct domains that evolve with different rates, different selective pressures, or may differ in codon bias. Instead of modeling these differences by more and more complex models of molecular evolution, we present a multipartition approach that allows maximum-likelihood phylogeny inference using different codon models at predefined partitions in the data. Partition models can, but do not have to, share free parameters in the estimation process. We test this approach ...[more]

PMID: 25911229

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Project description:This paper describes a targeted maximum likelihood estimator (TMLE) for the parameters of longitudinal static and dynamic marginal structural models. We consider a longitudinal data structure consisting of baseline covariates, time-dependent intervention nodes, intermediate time-dependent covariates, and a possibly time-dependent outcome. The intervention nodes at each time point can include a binary treatment as well as a right-censoring indicator. Given a class of dynamic or static interventions, a marginal structural model is used to model the mean of the intervention-specific counterfactual outcome as a function of the intervention, time point, and possibly a subset of baseline covariates. Because the true shape of this function is rarely known, the marginal structural model is used as a working model. The causal quantity of interest is defined as the projection of the true function onto this working model. Iterated conditional expectation double robust estimators for marginal structural model parameters were previously proposed by Robins (2000, 2002) and Bang and Robins (2005). Here we build on this work and present a pooled TMLE for the parameters of marginal structural working models. We compare this pooled estimator to a stratified TMLE (Schnitzer et al. 2014) that is based on estimating the intervention-specific mean separately for each intervention of interest. The performance of the pooled TMLE is compared to the performance of the stratified TMLE and the performance of inverse probability weighted (IPW) estimators using simulations. Concepts are illustrated using an example in which the aim is to estimate the causal effect of delayed switch following immunological failure of first line antiretroviral therapy among HIV-infected patients. Data from the International Epidemiological Databases to Evaluate AIDS, Southern Africa are analyzed to investigate this question using both TML and IPW estimators. Our results demonstrate practical advantages of the pooled TMLE over an IPW estimator for working marginal structural models for survival, as well as cases in which the pooled TMLE is superior to its stratified counterpart.

Dataset Information

Maximum-Likelihood Tree Estimation Using Codon Substitution Models with Multiple Partitions.

Publications

Maximum-Likelihood Tree Estimation Using Codon Substitution Models with Multiple Partitions.

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