14,337 research outputs found
Distributions associated with general runs and patterns in hidden Markov models
This paper gives a method for computing distributions associated with
patterns in the state sequence of a hidden Markov model, conditional on
observing all or part of the observation sequence. Probabilities are computed
for very general classes of patterns (competing patterns and generalized later
patterns), and thus, the theory includes as special cases results for a large
class of problems that have wide application. The unobserved state sequence is
assumed to be Markovian with a general order of dependence. An auxiliary Markov
chain is associated with the state sequence and is used to simplify the
computations. Two examples are given to illustrate the use of the methodology.
Whereas the first application is more to illustrate the basic steps in applying
the theory, the second is a more detailed application to DNA sequences, and
shows that the methods can be adapted to include restrictions related to
biological knowledge.Comment: Published in at http://dx.doi.org/10.1214/07-AOAS125 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
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
Parametric Inference for Biological Sequence Analysis
One of the major successes in computational biology has been the unification,
using the graphical model formalism, of a multitude of algorithms for
annotating and comparing biological sequences. Graphical models that have been
applied towards these problems include hidden Markov models for annotation,
tree models for phylogenetics, and pair hidden Markov models for alignment. A
single algorithm, the sum-product algorithm, solves many of the inference
problems associated with different statistical models. This paper introduces
the \emph{polytope propagation algorithm} for computing the Newton polytope of
an observation from a graphical model. This algorithm is a geometric version of
the sum-product algorithm and is used to analyze the parametric behavior of
maximum a posteriori inference calculations for graphical models.Comment: 15 pages, 4 figures. See also companion paper "Tropical Geometry of
Statistical Models" (q-bio.QM/0311009
The EM Algorithm and the Rise of Computational Biology
In the past decade computational biology has grown from a cottage industry
with a handful of researchers to an attractive interdisciplinary field,
catching the attention and imagination of many quantitatively-minded
scientists. Of interest to us is the key role played by the EM algorithm during
this transformation. We survey the use of the EM algorithm in a few important
computational biology problems surrounding the "central dogma"; of molecular
biology: from DNA to RNA and then to proteins. Topics of this article include
sequence motif discovery, protein sequence alignment, population genetics,
evolutionary models and mRNA expression microarray data analysis.Comment: Published in at http://dx.doi.org/10.1214/09-STS312 the Statistical
Science (http://www.imstat.org/sts/) by the Institute of Mathematical
Statistics (http://www.imstat.org
A decision-theoretic approach for segmental classification
This paper is concerned with statistical methods for the segmental
classification of linear sequence data where the task is to segment and
classify the data according to an underlying hidden discrete state sequence.
Such analysis is commonplace in the empirical sciences including genomics,
finance and speech processing. In particular, we are interested in answering
the following question: given data and a statistical model of
the hidden states , what should we report as the prediction under
the posterior distribution ? That is, how should you make a
prediction of the underlying states? We demonstrate that traditional approaches
such as reporting the most probable state sequence or most probable set of
marginal predictions can give undesirable classification artefacts and offer
limited control over the properties of the prediction. We propose a decision
theoretic approach using a novel class of Markov loss functions and report
via the principle of minimum expected loss (maximum expected
utility). We demonstrate that the sequence of minimum expected loss under the
Markov loss function can be enumerated exactly using dynamic programming
methods and that it offers flexibility and performance improvements over
existing techniques. The result is generic and applicable to any probabilistic
model on a sequence, such as Hidden Markov models, change point or product
partition models.Comment: Published in at http://dx.doi.org/10.1214/13-AOAS657 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Hybrid modeling, HMM/NN architectures, and protein applications
We describe a hybrid modeling approach where the parameters of a model are calculated and modulated by another model, typically a neural network (NN), to avoid both overfitting and underfitting. We develop the approach for the case of Hidden Markov Models (HMMs), by deriving a class of hybrid HMM/NN architectures. These architectures can be trained with unified algorithms that blend HMM dynamic programming with NN backpropagation. In the case of complex data, mixtures of HMMs or modulated HMMs must be used. NNs can then be applied both to the parameters of each single HMM, and to the switching or modulation of the models, as a function of input or context. Hybrid HMM/NN architectures provide a flexible NN parameterization for the control of model structure and complexity. At the same time, they can capture distributions that, in practice, are inaccessible to single HMMs. The HMM/NN hybrid approach is tested, in its simplest form, by constructing a model of the immunoglobulin protein family. A hybrid model is trained, and a multiple alignment derived, with less than a fourth of the number of parameters used with previous single HMMs
A Bayesian phylogenetic hidden Markov model for B cell receptor sequence analysis.
The human body generates a diverse set of high affinity antibodies, the soluble form of B cell receptors (BCRs), that bind to and neutralize invading pathogens. The natural development of BCRs must be understood in order to design vaccines for highly mutable pathogens such as influenza and HIV. BCR diversity is induced by naturally occurring combinatorial "V(D)J" rearrangement, mutation, and selection processes. Most current methods for BCR sequence analysis focus on separately modeling the above processes. Statistical phylogenetic methods are often used to model the mutational dynamics of BCR sequence data, but these techniques do not consider all the complexities associated with B cell diversification such as the V(D)J rearrangement process. In particular, standard phylogenetic approaches assume the DNA bases of the progenitor (or "naive") sequence arise independently and according to the same distribution, ignoring the complexities of V(D)J rearrangement. In this paper, we introduce a novel approach to Bayesian phylogenetic inference for BCR sequences that is based on a phylogenetic hidden Markov model (phylo-HMM). This technique not only integrates a naive rearrangement model with a phylogenetic model for BCR sequence evolution but also naturally accounts for uncertainty in all unobserved variables, including the phylogenetic tree, via posterior distribution sampling
Genomics and proteomics: a signal processor's tour
The theory and methods of signal processing are becoming increasingly important in molecular biology. Digital filtering techniques, transform domain methods, and Markov models have played important roles in gene identification, biological sequence analysis, and alignment. This paper contains a brief review of molecular biology, followed by a review of the applications of signal processing theory. This includes the problem of gene finding using digital filtering, and the use of transform domain methods in the study of protein binding spots. The relatively new topic of noncoding genes, and the associated problem of identifying ncRNA buried in DNA sequences are also described. This includes a discussion of hidden Markov models and context free grammars. Several new directions in genomic signal processing are briefly outlined in the end
HMM with auxiliary memory: a new tool for modeling RNA structures
For a long time, proteins have been believed to perform most of the important functions in all cells. However, recent results in genomics have revealed that many RNAs that do not encode proteins play crucial roles in the cell machinery. The so-called ncRNA genes that are transcribed into RNAs but not translated into proteins, frequently conserve their secondary structures more than they conserve their primary sequences. Therefore, in order to identify ncRNA genes, we have to take the secondary structure of RNAs into consideration. Traditional approaches that are mainly based on base-composition statistics cannot be used for modeling and identifying such structures and models with more descriptive power are required. In this paper, we introduce the concept of context-sensitive HMMs, which is capable of describing pairwise interactions between distant symbols. It is demonstrated that the proposed model can efficiently model various RNA secondary structures that are frequently observed
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