14,214 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
The Mathematics of Phylogenomics
The grand challenges in biology today are being shaped by powerful
high-throughput technologies that have revealed the genomes of many organisms,
global expression patterns of genes and detailed information about variation
within populations. We are therefore able to ask, for the first time,
fundamental questions about the evolution of genomes, the structure of genes
and their regulation, and the connections between genotypes and phenotypes of
individuals. The answers to these questions are all predicated on progress in a
variety of computational, statistical, and mathematical fields.
The rapid growth in the characterization of genomes has led to the
advancement of a new discipline called Phylogenomics. This discipline results
from the combination of two major fields in the life sciences: Genomics, i.e.,
the study of the function and structure of genes and genomes; and Molecular
Phylogenetics, i.e., the study of the hierarchical evolutionary relationships
among organisms and their genomes. The objective of this article is to offer
mathematicians a first introduction to this emerging field, and to discuss
specific mathematical problems and developments arising from phylogenomics.Comment: 41 pages, 4 figure
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
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
DNA ANALYSIS USING GRAMMATICAL INFERENCE
An accurate language definition capable of distinguishing between coding and non-coding DNA has important applications and analytical significance to the field of computational biology. The method proposed here uses positive sample grammatical inference and statistical information to infer languages for coding DNA.
An algorithm is proposed for the searching of an optimal subset of input sequences for the inference of regular grammars by optimizing a relevant accuracy metric. The algorithm does not guarantee the finding of the optimal subset; however, testing shows improvement in accuracy and performance over the basis algorithm.
Testing shows that the accuracy of inferred languages for components of DNA are consistently accurate. By using the proposed algorithm languages are inferred for coding DNA with average conditional probability over 80%. This reveals that languages for components of DNA can be inferred and are useful independent of the process that created them. These languages can then be analyzed or used for other tasks in computational biology.
To illustrate potential applications of regular grammars for DNA components, an inferred language for exon sequences is applied as post processing to Hidden Markov exon prediction to reduce the number of wrong exons detected and improve the specificity of the model significantly
An overview of the role of context-sensitive HMMs in the prediction of ncRNA genes
Non-coding RNAs (ncRNA) are RNA molecules that function in the cells without being translated into proteins. In recent years, much evidence has been found that ncRNAs play a crucial role in various biological processes. As a result, there has been an increasing interest in the prediction of ncRNA genes. Due to the conserved secondary structure in ncRNAs, there exist pairwise dependencies between distant bases. These dependencies cannot be effectively modeled using traditional HMMs, and we need a more complex model such as the context-sensitive HMM (csHMM). In this paper, we overview the role of csHMMs in the RNA secondary structure analysis and the prediction of ncRNA genes. It is demonstrated that the context-sensitive HMMs can serve as an efficient framework for these purposes
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
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
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