Integrating Overlapping Structures and Background Information of Words Significantly Improves Biological Sequence Comparison

Word-based models have achieved promising results in sequence comparison. However, as the important statistical properties of words in biological sequence, how to use the overlapping structures and background information of the words to improve sequence comparison is still a problem. This paper proposed a new statistical method that integrates the overlapping structures and the background information of the words in biological sequences. To assess the effectiveness of this integration for sequence comparison, two sets of evaluation experiments were taken to test the proposed model. The first one, performed via receiver operating curve analysis, is the application of proposed method in discrimination between functionally related regulatory sequences and unrelated sequences, intron and exon. The second experiment is to evaluate the performance of the proposed method with f-measure for clustering Hepatitis E virus genotypes. It was demonstrated that the proposed method integrating the overlapping structures and the background information of words significantly improves biological sequence comparison and outperforms the existing models

MS4 - Multi-Scale Selector of Sequence Signatures: An alignment-free method for classification of biological sequences

International audienc

ALIGNMENT-FREE METHODS AND ITS APPLICATIONS

Comparing biological sequences remains one of the most vital activities in Bioinformatics. Comparing biological sequences would address the relatedness between species, and find similar structures that might lead to similar functions. Sequence alignment is the default method, and has been used in the domain for over four decades. It gained a lot of trust, but limitations and even failure has been reported, especially with the new generated genomes. These new generated genomes have bigger size, and to some extent suffer errors. Such errors come mainly as a result from the sequencing machine. These sequencing errors should be considered when submitting sequences to GenBank, for sequence comparison, it is often hard to address or even trace this problem. Alignment-based methods would fail with such errors, and even if biologists still trust them, reports showed failure with these methods. The poor results of alignment-based methods with erratic sequences, motivated researchers in the domain to look for alternatives. These alternative methods are alignment-free, and would overcome the shortcomings of alignment-based methods. The work of this thesis is based on alignment-free methods, and it conducts an in-depth study to evaluate these methods, and find the right domain’s application for them. The right domain for alignment-free methods could be by applying them to data that were subjected to manufactured errors, and test the methods provide better comparison results with data that has naturally severe errors. The two techniques used in this work are compression-based and motif-based (or k-mer based, or signal based). We also addressed the selection of the used motifs in the second technique, and how to progress the results by selecting specific motifs that would enhance the quality of results. In addition, we applied an alignment-free method to a different domain, which is gene prediction. We are using alignment-free in gene prediction to speed up the process of providing high quality results, and predict accurate stretches in the DNA sequence, which would be considered parts of genes

Patterns and Signals of Biology: An Emphasis On The Role of Post Translational Modifications in Proteomes for Function and Evolutionary Progression

After synthesis, a protein is still immature until it has been customized for a specific task. Post-translational modifications (PTMs) are steps in biosynthesis to perform this customization of protein for unique functionalities. PTMs are also important to protein survival because they rapidly enable protein adaptation to environmental stress factors by conformation change. The overarching contribution of this thesis is the construction of a computational profiling framework for the study of biological signals stemming from PTMs associated with stressed proteins. In particular, this work has been developed to predict and detect the biological mechanisms involved in types of stress response with PTMs in mitochondrial (Mt) and non-Mt protein. Before any mechanism can be studied, there must first be some evidence of its existence. This evidence takes the form of signals such as biases of biological actors and types of protein interaction. Our framework has been developed to locate these signals, distilled from “Big Data” resources such as public databases and the the entire PubMed literature corpus. We apply this framework to study the signals to learn about protein stress responses involving PTMs, modification sites (MSs). We developed of this framework, and its approach to analysis, according to three main facets: (1) by statistical evaluation to determine patterns of signal dominance throughout large volumes of data, (2) by signal location to track down the regions where the mechanisms must be found according to the types and numbers of associated actors at relevant regions in protein, and (3) by text mining to determine how these signals have been previously investigated by researchers. The results gained from our framework enable us to uncover the PTM actors, MSs and protein domains which are the major components of particular stress response mechanisms and may play roles in protein malfunction and disease

An Improved String Composition Method for Sequence Comparison

Background: Historically, two categories of computational algorithms (alignment-based and alignment-free) have been applied to sequence comparison–one of the most fundamental issues in bioinformatics. Multiple sequence alignment, although dominantly used by biologists, possesses both fundamental as well as computational limitations. Consequently, alignment-free methods have been explored as important alternatives in estimating sequence similarity. Of the alignment-free methods, the string composition vector (CV) methods, which use the frequencies of nucleotide or amino acid strings to represent sequence information, show promising results in genome sequence comparison of prokaryotes. The existing CV-based methods, however, suffer certain statistical problems, thereby underestimating the amount of evolutionary information in genetic sequences. Results: We show that the existing string composition based methods have two problems, one related to the Markov model assumption and the other associated with the denominator of the frequency normalization equation. We propose an improved complete composition vector method under the assumption of a uniform and independent model to estimate sequence information contributing to selection for sequence comparison. Phylogenetic analyses using both simulated and experimental data sets demonstrate that our new method is more robust compared with existing counterparts and comparable in robustness with alignment-based methods. Conclusion: We observed two problems existing in the currently used string composition methods and proposed a new robust method for the estimation of evolutionary information of genetic sequences. In addition, we discussed that it might not be necessary to use relatively long strings to build a complete composition vector (CCV), due to the overlapping nature of vector strings with a variable length. We suggested a practical approach for the choice of an optimal string length to construct the CCV