Multiple Sequence Alignment Methods Research Articles

Improving multiple sequence alignment by using better guide trees.

Progressive sequence alignment is one of the most commonly used method for multiple sequence alignment. Roughly speaking, the method first builds a guide tree, and then aligns the sequences progressively according to the topology of the tree. It is believed that guide trees are very important to progressive alignment; a better guide tree will give an alignment with higher accuracy. Recently, we have proposed an adaptive method for constructing guide trees. This paper studies the quality of the guide trees constructed by such method. Our study showed that our adaptive method can be used to improve the accuracy of many different progressive MSA tools. In fact, we give evidences showing that the guide trees constructed by the adaptive method are among the best.

A new method to cluster DNA sequences using Fourier power spectrum.

A novel clustering method is proposed to classify genes and genomes. For a given DNA sequence, a binary indicator sequence of each nucleotide is constructed, and Discrete Fourier Transform is applied on these four sequences to attain respective power spectra. Mathematical moments are built from these spectra, and multidimensional vectors of real numbers are constructed from these moments. Cluster analysis is then performed in order to determine the evolutionary relationship between DNA sequences. The novelty of this method is that sequences with different lengths can be compared easily via the use of power spectra and moments. Experimental results on various datasets show that the proposed method provides an efficient tool to classify genes and genomes. It not only gives comparable results but also is remarkably faster than other multiple sequence alignment and alignment-free methods.

Promoter Sequence Analysis through No Gap Multiple Sequence Alignment of Motif Pairs

Abstract The advancement in the sequencing technology has led to exponential increase in the biological sequence data. Therefore the need for methods and techniques that analyze this sequence data are in demand. A central task in analysis of this data is sequence alignment. In this work, we present a new multiple sequence alignment method for analyzing the similarity/homology existing in the promoter sequences. We extract the motif pair feature from the binarized position specific motif matrix (PSMM) of each promoter pair or sets. We then compare the count of motif pairs between the promoter sequences to find the similarity. The efficacy of the proposed method is tested on two datasets obtained from NCBI. The results obtained agree with our understanding of organism similarity.

분할 순차 패턴과 SVM을 이용한 HPV 타입 예측 시스템

Abstract The existing system consumes a considerable amount time and cost for extracting the patterns from whole sequences or misaligned sequences. In this paper, We propose the classification system, which creates the partition sequence sections using multiple sequence alignment method and extracts the sequential patterns from these section. These extracted patterns are accumulated motif candidate sets and then used the training sets of SVM classifier. This proposed system predicts a HPV-type(high/low) using the learned knowledges from known/unknown protein sequences and shows more improved precision, recall than previous system in 30% minimum support. Key Words : Sequential Pattern, SVM, Motif, Protein Sequence, HPV risk Received 5 September 2014, Revised 13 October 2014Accepted 20 December 2014Corresponding Author: Jinsu Kim(College of Liberal Arts, Anyang University)Email: kjspace@anyang.ac.krⒸ The Society of Digital Policy & Management. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is ISSN: 1738-1916 properly cited.

Assessment and refinement of eukaryotic gene structure prediction with gene-structure-aware multiple protein sequence alignment.

BackgroundAccurate computational identification of eukaryotic gene organization is a long-standing problem. Despite the fundamental importance of precise annotation of genes encoded in newly sequenced genomes, the accuracy of predicted gene structures has not been critically evaluated, mostly due to the scarcity of proper assessment methods.ResultsWe present a gene-structure-aware multiple sequence alignment method for gene prediction using amino acid sequences translated from homologous genes from many genomes. The approach provides rich information concerning the reliability of each predicted gene structure. We have also devised an iterative method that attempts to improve the structures of suspiciously predicted genes based on a spliced alignment algorithm using consensus sequences or reliable homologs as templates. Application of our methods to cytochrome P450 and ribosomal proteins from 47 plant genomes indicated that 50 ~ 60 % of the annotated gene structures are likely to contain some defects. Whereas more than half of the defect-containing genes may be intrinsically broken, i.e. they are pseudogenes or gene fragments, located in unfinished sequencing areas, or corresponding to non-productive isoforms, the defects found in a majority of the remaining gene candidates can be remedied by our iterative refinement method.ConclusionsRefinement of eukaryotic gene structures mediated by gene-structure-aware multiple protein sequence alignment is a useful strategy to dramatically improve the overall prediction quality of a set of homologous genes. Our method will be applicable to various families of protein-coding genes if their domain structures are evolutionarily stable. It is also feasible to apply our method to gene families from all kingdoms of life, not just plants.

Proteolytic Processing of the Extracellular Scaffolding Protein LEV-9 Is Required for Clustering Acetylcholine Receptors

Correct positioning of neurotransmitter-gated receptors at postsynapses is essential for synaptic transmission. At Caenorhabditis elegans neuromuscular junctions, clustering of levamisole-sensitive acetylcholine receptors (L-AChRs) requires the muscle-secreted scaffolding protein LEV-9, a multidomain factor containing complement control protein (CCP) modules. Here we show that LEV-9 needs to be cleaved at its C terminus to exert its function. LEV-9 cleavage is not required for trafficking nor secretion but directly controls scaffolding activity. The cleavage site is evolutionarily conserved, and post-translational cleavage ensures the structural and functional decoupling between different isoforms encoded by the lev-9 gene. Data mining indicates that most human CCP-containing factors are likely cleaved C-terminally from CCP tandems, suggesting that not only domain architectures but also cleavage location can be conserved in distant architecturally related proteins.

A multiple sequence alignment method with sequence vectorization

Purpose – The time complexity of most multiple sequence alignment algorithm is O(N2) or O(N3) (N is the number of sequences). In addition, with the development of biotechnology, the amount of biological sequences grows significantly. The traditional methods have some difficulties in handling large-scale sequence. The proposed Lemk_MSA method aims to reduce the time complexity, especially for large-scale sequences. At the same time, it can keep similar accuracy level compared to the traditional methods. Design/methodology/approach – LemK_MSA converts multiple sequence alignment into corresponding 10D vector alignment by ten types of copy modes based on Lempel-Ziv. Then, it uses k-means algorithm and NJ algorithm to divide the sequences into several groups and calculate guide tree of each group. A complete guide tree for multiple sequence alignment could be constructed by merging guide tree of every group. Moreover, for large-scale multiple sequence, Lemk_MSA proposes a GPU-based parallel way for distance matrix calculation. Findings – Under this approach, the time efficiency to process multiple sequence alignment can be improved. The high-throughput mouse antibody sequences are used to validate the proposed method. Compared to ClustalW, MAFFT and Mbed, LemK_MSA is more than ten times efficient while ensuring the alignment accuracy at the same time. Originality/value – This paper proposes a novel method with sequence vectorization for multiple sequence alignment based on Lempel-Ziv. A GPU-based parallel method has been designed for large-scale distance matrix calculation. It provides a new way for multiple sequence alignment research.

Multiple sequence alignment with affine gap by using multi-objective genetic algorithm

Multiple sequence alignment is of central importance to bioinformatics and computational biology. Although a large number of algorithms for computing a multiple sequence alignment have been designed, the efficient computation of highly accurate and statistically significant multiple alignments is still a challenge. In this paper, we propose an efficient method by using multi-objective genetic algorithm (MSAGMOGA) to discover optimal alignments with affine gap in multiple sequence data. The main advantage of our approach is that a large number of tradeoff (i.e., non-dominated) alignments can be obtained by a single run with respect to conflicting objectives: affine gap penalty minimization and similarity and support maximization. To the best of our knowledge, this is the first effort with three objectives in this direction. The proposed method can be applied to any data set with a sequential character. Furthermore, it allows any choice of similarity measures for finding alignments. By analyzing the obtained optimal alignments, the decision maker can understand the tradeoff between the objectives. We compared our method with the three well-known multiple sequence alignment methods, MUSCLE, SAGA and MSA-GA. As the first of them is a progressive method, and the other two are based on evolutionary algorithms. Experiments on the BAliBASE 2.0 database were conducted and the results confirm that MSAGMOGA obtains the results with better accuracy statistical significance compared with the three well-known methods in aligning multiple sequence alignment with affine gap. The proposed method also finds solutions faster than the other evolutionary approaches mentioned above.

SVM-based Automatic Annotation of Multiple Sequence Alignments

Multiple Sequence alignments are a critical step in phylogeny inference. There is a lack of an appropriate approach which is capable of 1) finding the best global alignment and 2) automating and reproducing manual editing. Progressive alignment is an effective method for multiple Sequence alignments. However, its application in practice has also long been largely hampered because the alignment regions are not homologous to maximize the alignment score. The standard practice in phylogenetics involves manual editing of alignments and manual editing is a non-trivial task. Aiming at these problems, this study 1) uses SVM to capture the neighborhood of a site to automate and reproduce manual editing, and 2) builds the procedure of SVM Model Training and Automatic Annotation. Exper imental results demonstrate that a SVM-based classifier can reproduce the manual editing task s with an accuracy of 95.5%. This method is stable to both RBF parameters (Gamma and C) and clearly outperforms GBLOCKS and AL2CO, which are conventional editing/annotating methods. The classification accuracy achieved by the proposed method is always much higher than those achieved by the counterpart methods.

Evaluating the accuracy and efficiency of multiple sequence alignment methods.

A comparison of 10 most popular Multiple Sequence Alignment (MSA) tools, namely, MUSCLE, MAFFT(L-INS-i), MAFFT (FFT-NS-2), T-Coffee, ProbCons, SATe, Clustal Omega, Kalign, Multalin, and Dialign-TX is presented. We also focused on the significance of some implementations embedded in algorithm of each tool. Based on 10 simulated trees of different number of taxa generated by R, 400 known alignments and sequence files were constructed using indel-Seq-Gen. A total of 4000 test alignments were generated to study the effect of sequence length, indel size, deletion rate, and insertion rate. Results showed that alignment quality was highly dependent on the number of deletions and insertions in the sequences and that the sequence length and indel size had a weaker effect. Overall, ProbCons was consistently on the top of list of the evaluated MSA tools. SATe, being little less accurate, was 529.10% faster than ProbCons and 236.72% faster than MAFFT(L-INS-i). Among other tools, Kalign and MUSCLE achieved the highest sum of pairs. We also considered BALiBASE benchmark datasets and the results relative to BAliBASE- and indel-Seq-Gen-generated alignments were consistent in the most cases.

An alignment-free method to find similarity among protein sequences via the general form of Chou’s pseudo amino acid composition

In this paper, we propose a method to create the 60-dimensional feature vector for protein sequences via the general form of pseudo amino acid composition. The construction of the feature vector is based on the contents of amino acids, total distance of each amino acid from the first amino acid in the protein sequence and the distribution of 20 amino acids. The obtained cosine distance metric (also called the similarity matrix) is used to construct the phylogenetic tree by the neighbour joining method. In order to show the applicability of our approach, we tested it on three proteins: 1) ND5 protein sequences from nine species, 2) ND6 protein sequences from eight species, and 3) 50 coronavirus spike proteins. The results are in agreement with known history and the output from the multiple sequence alignment program ClustalW, which is widely used. We have also compared our phylogenetic results with six other recently proposed alignment-free methods. These comparisons show that our proposed method gives a more consistent biological relationship than the others. In addition, the time complexity is linear and space required is less as compared with other alignment-free methods that use graphical representation. It should be noted that the multiple sequence alignment method has exponential time complexity.

Designing a parallel cloud based comparative genomics workflow to improve phylogenetic analyses

Over the last years, comparative genomics analyses have become more compute-intensive due to the explosive number of available genome sequences. Comparative genomics analysis is an important a prioristep for experiments in various bioinformatics domains. This analysis can be used to enhance the performance and quality of experiments in areas such as evolution and phylogeny. A common phylogenetic analysis makes extensive use of Multiple Sequence Alignment (MSA) in the construction of phylogenetic trees, which are used to infer evolutionary relationships between homologous genes. Each phylogenetic analysis aims at exploring several different MSA methods to verify which execution produces trees with the best quality. This phylogenetic exploration may run during weeks, even when executed in High Performance Computing (HPC) environments. Although there are many approaches that model and parallelize phylogenetic analysis as scientific workflows, exploring all MSA methods becomes a complex and expensive task to be performed. If scientists determine a priorithe most adequate MSA method to use in the phylogenetic analysis, it would save time, and, in some cases, financial resources. Comparative genomics analyses play an important role in optimizing phylogenetic analysis workflows. In this paper, we extend the SciHmm scientific workflow, aimed at determining the most suitable MSA method, to use it in a phylogenetic analysis. SciHmm uses SciCumulus, a cloud workflow execution engine, for parallel execution. Experimental results show that using SciHmm considerably reduces the total execution time of the phylogenetic analysis (up to 80%). Experiments also show that trees built with the MSA program elected by using SciHmm presented more quality than the remaining, as expected. In addition, the parallel execution of SciHmm shows that this kind of bioinformatics workflow has an excellent cost/benefit when executed in cloud environments.

Biggest challenges in bioinformatics

The third Heidelberg Unseminars in Bioinformatics (HUB) was held on 18th October 2012, at Heidelberg University, Germany. HUB brought together around 40 bioinformaticians from academia and industry to discuss the 'Biggest Challenges in Bioinformatics' in a 'World Café' style event.

A data parallel strategy for aligning multiple biological sequences on multi-core computers

In this paper, we address the large-scale biological sequence alignment problem, which has an increasing demand in computational biology. We employ data parallelism paradigm that is suitable for handling large-scale processing on multi-core computers to achieve a high degree of parallelism. Using the data parallelism paradigm, we propose a general strategy which can be used to speed up any multiple sequence alignment method. We applied five different clustering algorithms in our strategy and implemented rigorous tests on an 8-core computer using four traditional benchmarks and artificially generated sequences. The results show that our multi-core-based implementations can achieve up to 151-fold improvements in execution time while losing 2.19% accuracy on average. The source code of the proposed strategy, together with the test sets used in our analysis, is available on request.

LemK_MSA: A Multiple Sequence Alignment Method with Sequence Vectorization Based on Lempel-Ziv

In this paper, we propose a method for multiple sequence alignment, LemK_MSA, which integrates Lempel-Ziv based sequence vectorization and k-means clustering analysis. LemK_MSA converts multiple sequence alignment into corresponding 10-dimensional vector alignment by 10 types of copy modes. Then it uses k-means algorithm and NJ algorithm to divide the sequences into several groups and calculate guide tree of each part with the vectors of the sequences. A complete guide tree for multiple sequence alignment could be constructed by merging guide tree of every group. Thus, the time efficiency of processing multiple sequence alignment, especially for large-scale sequences, can be improved. The high-throughput mouse antibody sequences are used to validate the proposed method. Compared to ClustalW, MAFFT and Mbed, LemK_MSA is more than ten times efficient while ensuring the alignment accuracy at the same time. LemK_MSA also provides an effective method to analyze the evolutionary relationship and structural features among high-throughput sequences.

Class of Multiple Sequence Alignment Algorithm Affects Genomic Analysis

Multiple sequence alignment (MSA) is the heart of comparative sequence analysis. Recent studies demonstrate that MSA algorithms can produce different outcomes when analyzing genomes, including phylogenetic tree inference and the detection of adaptive evolution. These studies also suggest that the difference between MSA algorithms is of a similar order to the uncertainty within an algorithm and suggest integrating across this uncertainty. In this study, we examine further the problem of disagreements between MSA algorithms and how they affect downstream analyses. We also investigate whether integrating across alignment uncertainty affects downstream analyses. We address these questions by analyzing 200 chordate gene families, with properties reflecting those used in large-scale genomic analyses. We find that newly developed distance metrics reveal two significantly different classes of MSA methods (MSAMs). The similarity-based class includes progressive aligners and consistency aligners, representing many methodological innovations for sequence alignment, whereas the evolution-based class includes phylogenetically aware alignment and statistical alignment. We proceed to show that the class of an MSAM has a substantial impact on downstream analyses. For phylogenetic inference, tree estimates and their branch lengths appear highly dependent on the class of aligner used. The number of families, and the sites within those families, inferred to have undergone adaptive evolution depend on the class of aligner used. Similarity-based aligners tend to identify more adaptive evolution. We also develop and test methods for incorporating MSA uncertainty when detecting adaptive evolution but find that although accounting for MSA uncertainty does affect downstream analyses, it appears less important than the class of aligner chosen. Our results demonstrate the critical role that MSA methodology has on downstream analysis, highlighting that the class of aligner chosen in an analysis has a demonstrable effect on its outcome.

MEGA-CC: computing core of molecular evolutionary genetics analysis program for automated and iterative data analysis

There is a growing need in the research community to apply the molecular evolutionary genetics analysis (MEGA) software tool for batch processing a large number of datasets and to integrate it into analysis workflows. Therefore, we now make available the computing core of the MEGA software as a stand-alone executable (MEGA-CC), along with an analysis prototyper (MEGA-Proto). MEGA-CC provides users with access to all the computational analyses available through MEGA's graphical user interface version. This includes methods for multiple sequence alignment, substitution model selection, evolutionary distance estimation, phylogeny inference, substitution rate and pattern estimation, tests of natural selection and ancestral sequence inference. Additionally, we have upgraded the source code for phylogenetic analysis using the maximum likelihood methods for parallel execution on multiple processors and cores. Here, we describe MEGA-CC and outline the steps for using MEGA-CC in tandem with MEGA-Proto for iterative and automated data analysis. http://www.megasoftware.net/.

Conservation of a Triple-Helix-Forming RNA Stability Element in Noncoding and Genomic RNAs of Diverse Viruses

Abundant expression of the long noncoding (lnc) PAN (polyadenylated nuclear) RNA by the human oncogenic gammaherpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) depends on a cis-element called the expression and nuclear retention element (ENE). The ENE upregulates PAN RNA by inhibiting its rapid nuclear decay through triple-helix formation with the poly(A) tail. Using structure-based bioinformatics, we identified six ENE-like elements in evolutionarily diverse viral genomes. Five are in double-stranded DNA viruses, including mammalian herpesviruses, insect polydnaviruses, and a protist mimivirus. One is in an insect picorna-like positive-strand RNA virus, suggesting that the ENE can counteract cytoplasmic as well as nuclear RNA decay pathways. Functionality of four of the ENEs was demonstrated by increased accumulation of an intronless polyadenylated reporter transcript in human cells. Identification of these ENEs enabled the discovery of PAN RNA homologs in two additional gammaherpesviruses, RRV and EHV2. Our findings demonstrate that searching for structural elements can lead to rapid identification of lncRNAs.

Cluster Analysis Method for Multiple Sequence Alignment

the addition of more data in the field of proteomics, the computational methods need to be more efficient. The fraction or the part of molecular sequence that is more resistant to change is functionally more important to the molecule. Comparative approaches are used to ensure the reliability of sequence alignment. The problem of multiple sequence alignment (MSA) is a proposition of evolutionary history. The explicit homologous correspondence of each individual sequence position is established for each column in the alignment. In the present work, the different pair-wise sequence alignment methods are discussed. The limitation of these methods is that they are capable for aligning the limited number of sequences having small sequence length. A new method is proposed for sequence alignment based on the local alignment with consensus sequence. The triticum wheat varieties sequences are considered which are loaded from the NCBI databank. The dataset is divided into two parts and two phylogenetic trees are constructed for each dataset. Using advanced pruning techniques, a single tree is constructed from the two trees generated. Then by applying the threshold condition, the closely related sequences are extracted and optimal MSA is obtained using shift operations in both directions.

Formula omitted]-MSA — A GPU-based, fast and accurate algorithm for multiple sequence alignment

Multiple sequence alignment (MSA) methods are essential in biological analysis. Several MSA algorithms have been proposed in recent years. The quality of the results produced by those methods is reasonable, but there is no single method that consistently outperforms others. Additionally, the increasing number of sequences in the biological databases is perceived as one of the upcoming challenges for alignment methods in the nearest future. The lack of performance concerns not only the alignment problems, but may be observed in many areas of biologically related research.To overcome this problem in the field of pairwise alignment, several GPU (Graphics Processing Unit) computing approaches have been proposed lately. These solutions show a great potential of GPU platform. Therefore, our main idea was to design and implement an MSA method which can take advantage of modern graphics cards. Our solution is based on T-Coffee–well known for its high accuracy MSA algorithm. Its computational time, however, is often unacceptable. Performed tests show that our method, named G-MSA, is highly efficient achieving up to 193-fold speedup on a single GPU while the quality of its results remains very good. Due to effective memory usage the method can perform alignment for huge sets of sequences that previously could only be aligned on computer clusters. Moreover, multiple GPUs support with load balancing makes the application very scalable.