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

Large-scale annotation of proteins with labelling methods

We revise a major important problem in bioinformatics: how to annotate protein sequences in the genomic era and all the solutions that have been described by implementing tools based on labelling methods. In this paper we mainly focus on our own work and the theoretical methods that are popular in the field of biosequence analysis in modern molecular biology. We will also review a recent application from our group that largely improves on the topology prediction of disulfide bonds in proteins from Eukaryotic organisms

Hidden Markov Models for Gene Sequence Classification: Classifying the VSG genes in the Trypanosoma brucei Genome

The article presents an application of Hidden Markov Models (HMMs) for pattern recognition on genome sequences. We apply HMM for identifying genes encoding the Variant Surface Glycoprotein (VSG) in the genomes of Trypanosoma brucei (T. brucei) and other African trypanosomes. These are parasitic protozoa causative agents of sleeping sickness and several diseases in domestic and wild animals. These parasites have a peculiar strategy to evade the host's immune system that consists in periodically changing their predominant cellular surface protein (VSG). The motivation for using patterns recognition methods to identify these genes, instead of traditional homology based ones, is that the levels of sequence identity (amino acid and DNA sequence) amongst these genes is often below of what is considered reliable in these methods. Among pattern recognition approaches, HMM are particularly suitable to tackle this problem because they can handle more naturally the determination of gene edges. We evaluate the performance of the model using different number of states in the Markov model, as well as several performance metrics. The model is applied using public genomic data. Our empirical results show that the VSG genes on T. brucei can be safely identified (high sensitivity and low rate of false positives) using HMM.Comment: Accepted article in July, 2015 in Pattern Analysis and Applications, Springer. The article contains 23 pages, 4 figures, 8 tables and 51 reference

Developing and applying heterogeneous phylogenetic models with XRate

Modeling sequence evolution on phylogenetic trees is a useful technique in computational biology. Especially powerful are models which take account of the heterogeneous nature of sequence evolution according to the "grammar" of the encoded gene features. However, beyond a modest level of model complexity, manual coding of models becomes prohibitively labor-intensive. We demonstrate, via a set of case studies, the new built-in model-prototyping capabilities of XRate (macros and Scheme extensions). These features allow rapid implementation of phylogenetic models which would have previously been far more labor-intensive. XRate's new capabilities for lineage-specific models, ancestral sequence reconstruction, and improved annotation output are also discussed. XRate's flexible model-specification capabilities and computational efficiency make it well-suited to developing and prototyping phylogenetic grammar models. XRate is available as part of the DART software package: http://biowiki.org/DART .Comment: 34 pages, 3 figures, glossary of XRate model terminolog

PhyloFacts: an online structural phylogenomic encyclopedia for protein functional and structural classification

The Berkeley Phylogenomics Group presents PhyloFacts, a structural phylogenomic encyclopedia containing almost 10,000 'books' for protein families and domains, with pre-calculated structural, functional and evolutionary analyses. PhyloFacts enables biologists to avoid the systematic errors associated with function prediction by homology through the integration of a variety of experimental data and bioinformatics methods in an evolutionary framework. Users can submit sequences for classification to families and functional subfamilies. PhyloFacts is available as a worldwide web resource from

Inference with Constrained Hidden Markov Models in PRISM

A Hidden Markov Model (HMM) is a common statistical model which is widely used for analysis of biological sequence data and other sequential phenomena. In the present paper we show how HMMs can be extended with side-constraints and present constraint solving techniques for efficient inference. Defining HMMs with side-constraints in Constraint Logic Programming have advantages in terms of more compact expression and pruning opportunities during inference. We present a PRISM-based framework for extending HMMs with side-constraints and show how well-known constraints such as cardinality and all different are integrated. We experimentally validate our approach on the biologically motivated problem of global pairwise alignment

Applications of Hidden Markov Models in Microarray Gene Expression Data

Hidden Markov models (HMMs) are well developed statistical models to capture hidden information from observable sequential symbols. They were first used in speech recognition in 1970s and have been successfully applied to the analysis of biological sequences since late 1980s as in finding protein secondary structure, CpG islands and families of related DNA or protein sequences [1]. In a HMM, the system being modeled is assumed to be a Markov process with unknown parameters, and the challenge is to determine the hidden parameters from the observable parameters. In this chapter, we described two applications using HMMs to predict gene functions in yeast and DNA copy number alternations in human tumor cells, based on gene expression microarray data