25,347 research outputs found
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
Identification and utilization of arbitrary correlations in models of recombination signal sequences
BACKGROUND: A significant challenge in bioinformatics is to develop methods for detecting and modeling patterns in variable DNA sequence sites, such as protein-binding sites in regulatory DNA. Current approaches sometimes perform poorly when positions in the site do not independently affect protein binding. We developed a statistical technique for modeling the correlation structure in variable DNA sequence sites. The method places no restrictions on the number of correlated positions or on their spatial relationship within the site. No prior empirical evidence for the correlation structure is necessary. RESULTS: We applied our method to the recombination signal sequences (RSS) that direct assembly of B-cell and T-cell antigen-receptor genes via V(D)J recombination. The technique is based on model selection by cross-validation and produces models that allow computation of an information score for any signal-length sequence. We also modeled RSS using order zero and order one Markov chains. The scores from all models are highly correlated with measured recombination efficiencies, but the models arising from our technique are better than the Markov models at discriminating RSS from non-RSS. CONCLUSIONS: Our model-development procedure produces models that estimate well the recombinogenic potential of RSS and are better at RSS recognition than the order zero and order one Markov models. Our models are, therefore, valuable for studying the regulation of both physiologic and aberrant V(D)J recombination. The approach could be equally powerful for the study of promoter and enhancer elements, splice sites, and other DNA regulatory sites that are highly variable at the level of individual nucleotide positions
Analysis of Gene Evolution: the software AGE
The software AGE (Analysis of Gene Evolution) has been developed both to study a genetic reality, i. e. the identification of statistical properties in genes (e.g. periodicities), and to simulate this observed genetic reality, by models of molecular evolution. AGE has two types of models: (i) models of sequence creation from oligonucleotides: concatenation model in series of an oligonucleotide, independent (or Markov) mixing model of oligonucleotides according to given probabilities (or a Markov matrix); (ii) models of sequence evolution from created sequences: insertion/deletion process of (mono, di, tri)nucleot-ides, base mutation process. The study of a reality and the development of simulation models are based on several new algorithms: approximated simulation and exact calculus to compute various autocorrelation functions, Fourier transformation of autocorrelation curves, recognition of a curve form, etc. AGE is implemented on IBM or compatible microcomputers and can be used by biologists without any computer knowledge to identify statistical properties in their newly determined DNA sequence and to explain them by models of molecular evolutio
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
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
Computing the likelihood of sequence segmentation under Markov modelling
I tackle the problem of partitioning a sequence into homogeneous segments,
where homogeneity is defined by a set of Markov models. The problem is to study
the likelihood that a sequence is divided into a given number of segments.
Here, the moments of this likelihood are computed through an efficient
algorithm. Unlike methods involving Hidden Markov Models, this algorithm does
not require probability transitions between the models. Among many possible
usages of the likelihood, I present a maximum \textit{a posteriori} probability
criterion to predict the number of homogeneous segments into which a sequence
can be divided, and an application of this method to find CpG islands
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