Detection of recombination in DNA multiple alignments with hidden markov models

CConventional phylogenetic tree estimation methods assume that all sites in a DNA multiple alignment have the same evolutionary history. This assumption is violated in data sets from certain bacteria and viruses due to recombination, a process that leads to the creation of mosaic sequences from different strains and, if undetected, causes systematic errors in phylogenetic tree estimation. In the current work, a hidden Markov model (HMM) is employed to detect recombination events in multiple alignments of DNA sequences. The emission probabilities in a given state are determined by the branching order (topology) and the branch lengths of the respective phylogenetic tree, while the transition probabilities depend on the global recombination probability. The present study improves on an earlier heuristic parameter optimization scheme and shows how the branch lengths and the recombination probability can be optimized in a maximum likelihood sense by applying the expectation maximization (EM) algorithm. The novel algorithm is tested on a synthetic benchmark problem and is found to clearly outperform the earlier heuristic approach. The paper concludes with an application of this scheme to a DNA sequence alignment of the argF gene from four Neisseria strains, where a likely recombination event is clearly detected

A generalized risk approach to path inference based on hidden Markov models

Motivated by the unceasing interest in hidden Markov models (HMMs), this paper re-examines hidden path inference in these models, using primarily a risk-based framework. While the most common maximum a posteriori (MAP), or Viterbi, path estimator and the minimum error, or Posterior Decoder (PD), have long been around, other path estimators, or decoders, have been either only hinted at or applied more recently and in dedicated applications generally unfamiliar to the statistical learning community. Over a decade ago, however, a family of algorithmically defined decoders aiming to hybridize the two standard ones was proposed (Brushe et al., 1998). The present paper gives a careful analysis of this hybridization approach, identifies several problems and issues with it and other previously proposed approaches, and proposes practical resolutions of those. Furthermore, simple modifications of the classical criteria for hidden path recognition are shown to lead to a new class of decoders. Dynamic programming algorithms to compute these decoders in the usual forward-backward manner are presented. A particularly interesting subclass of such estimators can be also viewed as hybrids of the MAP and PD estimators. Similar to previously proposed MAP-PD hybrids, the new class is parameterized by a small number of tunable parameters. Unlike their algorithmic predecessors, the new risk-based decoders are more clearly interpretable, and, most importantly, work "out of the box" in practice, which is demonstrated on some real bioinformatics tasks and data. Some further generalizations and applications are discussed in conclusion.Comment: Section 5: corrected denominators of the scaled beta variables (pp. 27-30), => corrections in claims 1, 3, Prop. 12, bottom of Table 1. Decoder (49), Corol. 14 are generalized to handle 0 probabilities. Notation is more closely aligned with (Bishop, 2006). Details are inserted in eqn-s (43); the positivity assumption in Prop. 11 is explicit. Fixed typing errors in equation (41), Example

Accuracy of MAP segmentation with hidden Potts and Markov mesh prior models via Path Constrained Viterbi Training, Iterated Conditional Modes and Graph Cut based algorithms

In this paper, we study statistical classification accuracy of two different Markov field environments for pixelwise image segmentation, considering the labels of the image as hidden states and solving the estimation of such labels as a solution of the MAP equation. The emission distribution is assumed the same in all models, and the difference lays in the Markovian prior hypothesis made over the labeling random field. The a priori labeling knowledge will be modeled with a) a second order anisotropic Markov Mesh and b) a classical isotropic Potts model. Under such models, we will consider three different segmentation procedures, 2D Path Constrained Viterbi training for the Hidden Markov Mesh, a Graph Cut based segmentation for the first order isotropic Potts model, and ICM (Iterated Conditional Modes) for the second order isotropic Potts model. We provide a unified view of all three methods, and investigate goodness of fit for classification, studying the influence of parameter estimation, computational gain, and extent of automation in the statistical measures Overall Accuracy, Relative Improvement and Kappa coefficient, allowing robust and accurate statistical analysis on synthetic and real-life experimental data coming from the field of Dental Diagnostic Radiography. All algorithms, using the learned parameters, generate good segmentations with little interaction when the images have a clear multimodal histogram. Suboptimal learning proves to be frail in the case of non-distinctive modes, which limits the complexity of usable models, and hence the achievable error rate as well. All Matlab code written is provided in a toolbox available for download from our website, following the Reproducible Research Paradigm

Bayesian Detection of Changepoints in Finite-State Markov Chains for Multiple Sequences

We consider the analysis of sets of categorical sequences consisting of piecewise homogeneous Markov segments. The sequences are assumed to be governed by a common underlying process with segments occurring in the same order for each sequence. Segments are defined by a set of unobserved changepoints where the positions and number of changepoints can vary from sequence to sequence. We propose a Bayesian framework for analyzing such data, placing priors on the locations of the changepoints and on the transition matrices and using Markov chain Monte Carlo (MCMC) techniques to obtain posterior samples given the data. Experimental results using simulated data illustrates how the methodology can be used for inference of posterior distributions for parameters and changepoints, as well as the ability to handle considerable variability in the locations of the changepoints across different sequences. We also investigate the application of the approach to sequential data from two applications involving monsoonal rainfall patterns and branching patterns in trees