Propositionalisation of multiple sequence alignments using probabilistic models

Multiple sequence alignments play a central role in Bioinformatics. Most alignment representations are designed to facilitate knowledge extraction by human experts. Additionally statistical models like Profile Hidden Markov Models are used as representations. They offer the advantage to provide sound, probabilistic scores. The basic idea we present in this paper is to use the structure of a Profile Hidden Markov Model for propositionalisation. This way we get a simple, extendable representation of multiple sequence alignments which facilitates further analysis by Machine Learning algorighms

HMM word-to-phrase alignment with dependency constraints

In this paper, we extend the HMMwordto-phrase alignment model with syntactic dependency constraints. The syntactic dependencies between multiple words in one language are introduced into the model in a bid to produce coherent alignments. Our experimental results on a variety of Chinese–English data show that our syntactically constrained model can lead to as much as a 3.24% relative improvement in BLEU score over current HMM word-to-phrase alignment models on a Phrase-Based Statistical Machine Translation system when the training data is small, and a comparable performance compared to IBM model 4 on a Hiero-style system with larger training data. An intrinsic alignment quality evaluation shows that our alignment model with dependency constraints leads to improvements in both precision (by 1.74% relative) and recall (by 1.75% relative) over the model without dependency information

Pairwise statistical significance of local sequence alignment using multiple parameter sets and empirical justification of parameter set change penalty

Background: Accurate estimation of statistical significance of a pairwise alignment is an important problem in sequence comparison. Recently, a comparative study of pairwise statistical significance with database statistical significance was conducted. In this paper, we extend the earlier work on pairwise statistical significance by incorporating with it the use of multiple parameter sets. Results: Results for a knowledge discovery application of homology detection reveal that using multiple parameter sets for pairwise statistical significance estimates gives better coverage than using a single parameter set, at least at some error levels. Further, the results of pairwise statistical significance using multiple parameter sets are shown to be significantly better than database statistical significance estimates reported by BLAST and PSI-BLAST, and comparable and at times significantly better than SSEARCH. Using non-zero parameter set change penalty values give better performance than zero penalty. Conclusion: The fact that the homology detection performance does not degrade when using multiple parameter sets is a strong evidence for the validity of the assumption that the alignment score distribution follows an extreme value distribution even when using multiple parameter sets. Parameter set change penalty is a useful parameter for alignment using multiple parameter sets. Pairwise statistical significance using multiple parameter sets can be effectively used to determine the relatedness of a (or a few) pair(s) of sequences without performing a time-consuming database search

Comparison of ontology alignment systems across single matching task via the McNemar's test

Ontology alignment is widely-used to find the correspondences between different ontologies in diverse fields.After discovering the alignments,several performance scores are available to evaluate them.The scores typically require the identified alignment and a reference containing the underlying actual correspondences of the given ontologies.The current trend in the alignment evaluation is to put forward a new score(e.g., precision, weighted precision, etc.)and to compare various alignments by juxtaposing the obtained scores. However,it is substantially provocative to select one measure among others for comparison.On top of that, claiming if one system has a better performance than one another cannot be substantiated solely by comparing two scalars.In this paper,we propose the statistical procedures which enable us to theoretically favor one system over one another.The McNemar's test is the statistical means by which the comparison of two ontology alignment systems over one matching task is drawn.The test applies to a 2x2 contingency table which can be constructed in two different ways based on the alignments,each of which has their own merits/pitfalls.The ways of the contingency table construction and various apposite statistics from the McNemar's test are elaborated in minute detail.In the case of having more than two alignment systems for comparison, the family-wise error rate is expected to happen. Thus, the ways of preventing such an error are also discussed.A directed graph visualizes the outcome of the McNemar's test in the presence of multiple alignment systems.From this graph, it is readily understood if one system is better than one another or if their differences are imperceptible.The proposed statistical methodologies are applied to the systems participated in the OAEI 2016 anatomy track, and also compares several well-known similarity metrics for the same matching problem

Statistical Methods for Conservation and Alignment Quality in Proteins

Construction of multiple sequence alignments is a fundamental task in Bioinformatics. Multiple sequence alignments are used as a prerequisite in many Bioinformatics methods, and subsequently the quality of such methods can be critically dependent on the quality of the alignment. However, automatic construction of a multiple sequence alignment for a set of remotely related sequences does not always provide biologically relevant alignments.Therefore, there is a need for an objective approach for evaluating the quality of automatically aligned sequences. The profile hidden Markov model is a powerful approach in comparative genomics. In the profile hidden Markov model, the symbol probabilities are estimated at each conserved alignment position. This can increase the dimension of parameter space and cause an overfitting problem. These two research problems are both related to conservation. We have developed statistical measures for quantifying the conservation of multiple sequence alignments. Two types of methods are considered, those identifying conserved residues in an alignment position, and those calculating positional conservation scores. The positional conservation score was exploited in a statistical prediction model for assessing the quality of multiple sequence alignments. The residue conservation score was used as part of the emission probability estimation method proposed for profile hidden Markov models. The results of the predicted alignment quality score highly correlated with the correct alignment quality scores, indicating that our method is reliable for assessing the quality of any multiple sequence alignment. The comparison of the emission probability estimation method with the maximum likelihood method showed that the number of estimated parameters in the model was dramatically decreased, while the same level of accuracy was maintained. To conclude, we have shown that conservation can be successfully used in the statistical model for alignment quality assessment and in the estimation of emission probabilities in the profile hidden Markov models.Siirretty Doriast

BEAST: Bayesian evolutionary analysis by sampling trees

<p>Abstract</p> <p>Background</p> <p>The evolutionary analysis of molecular sequence variation is a statistical enterprise. This is reflected in the increased use of probabilistic models for phylogenetic inference, multiple sequence alignment, and molecular population genetics. Here we present BEAST: a fast, flexible software architecture for Bayesian analysis of molecular sequences related by an evolutionary tree. A large number of popular stochastic models of sequence evolution are provided and tree-based models suitable for both within- and between-species sequence data are implemented.</p> <p>Results</p> <p>BEAST version 1.4.6 consists of 81000 lines of Java source code, 779 classes and 81 packages. It provides models for DNA and protein sequence evolution, highly parametric coalescent analysis, relaxed clock phylogenetics, non-contemporaneous sequence data, statistical alignment and a wide range of options for prior distributions. BEAST source code is object-oriented, modular in design and freely available at <url>http://beast-mcmc.googlecode.com/</url> under the GNU LGPL license.</p> <p>Conclusion</p> <p>BEAST is a powerful and flexible evolutionary analysis package for molecular sequence variation. It also provides a resource for the further development of new models and statistical methods of evolutionary analysis.</p

Fast Statistical Alignment

We describe a new program for the alignment of multiple biological sequences that is both statistically motivated and fast enough for problem sizes that arise in practice. Our Fast Statistical Alignment program is based on pair hidden Markov models which approximate an insertion/deletion process on a tree and uses a sequence annealing algorithm to combine the posterior probabilities estimated from these models into a multiple alignment. FSA uses its explicit statistical model to produce multiple alignments which are accompanied by estimates of the alignment accuracy and uncertainty for every column and character of the alignment—previously available only with alignment programs which use computationally-expensive Markov Chain Monte Carlo approaches—yet can align thousands of long sequences. Moreover, FSA utilizes an unsupervised query-specific learning procedure for parameter estimation which leads to improved accuracy on benchmark reference alignments in comparison to existing programs. The centroid alignment approach taken by FSA, in combination with its learning procedure, drastically reduces the amount of false-positive alignment on biological data in comparison to that given by other methods. The FSA program and a companion visualization tool for exploring uncertainty in alignments can be used via a web interface at http://orangutan.math.berkeley.edu/fsa/, and the source code is available at http://fsa.sourceforge.net/