Benchmark of algorithms for multiple DNA sequence alignment across livestock species

Multiple sequence alignment (MSA) methods infer the homologous regions within DNA and protein sequences. Among the other algorithms for MSA, the center star method (CSM) is useful when processing a large number of sequences. In this method, the partially conserved regions among the non-center sequences tend to hide in the alignment. Therefore, existence of subsets of similar sequences in the input set leads to a significant accuracy loss. As a solution to the above problem, this research introduces an algorithm for MSA based on a solution proposed by D. Gusfield in 1991. In this research, the sequences are first grouped into subsets, aligned separately using CSM and finally these alignments are merged by applying progressive alignment procedure. The detailed solution for this problem is presented in the following section.

A large number of methods for multiple sequence alignment are currently available. Recent benchmarking tests demonstrated that strengths and drawbacks of these methods differ substantially. Global strategies can be outperformed by approaches based on local similarities and vice versa, depending on the characteristics of the input sequences. In recent years, mixed approaches that include both global and local features have shown promising results. Herein, we introduce a new algorithm for multiple sequence alignment that integrates the global divide-and-conquer approach with the local segment-based approach, thereby combining the strengths of those two strategies.

With the development of new sequencing techniques, whole genomes of many species have become available. This huge amount of data gives rise to new opportunities and challenges. These new sequences provide valuable information on relationships among species, e.g. genome recombination and conservation. One of the principal ways to investigate such information is multiple sequence alignment (MSA). Currently, there is large amount of MSA data on the internet, such as the UCSC genome database, but how to effectively use this information to solve classical and new problems is still an area lacking of exploration. In this thesis, we explored how to use this information in four problems, i.e. sequence orthology search problem, multiple alignment improvement problem, short read mapping problem, and genome rearrangement inference problem. For the first problem, we developed a EM algorithm to iteratively align a query with a multiple alignment database with the information from a phylogeny relating the query species and the species in the multiple alignment. We also infer the query's location in the phylogeny. We showed that by doing alignment and phylogeny inference together, we can improve the accuracies for both problems. For the second problem, we developed an optimization algorithm to iteratively refine the multiple alignment quality. Experiment results showed our algorithm is very stable in term of resulting alignments. The results showed that our method is more accurate than existing methods, i.e. Mafft, Clustal-O, and Mavid, on test data from three sets of species from the UCSC genome database. For the third problem, we developed a model, PhyMap, to align a read to a multiple alignment allowing mismatches and indels. PhyMap computes local alignments of a query sequence against a fixed multiple-genome alignment of closely related species. PhyMap uses a known phylogenetic tree on the species in the multiple alignment to improve the quality of its computed alignments while also estimating the placement of the query on this tree. Both theoretical computation and experiment results show that our model can differentiate between orthologous and paralogous alignments better than other popular short read mapping tools (BWA, BOWTIE and BLAST). For the fourth problem, we gave a simple genome recombination model which can express insertions, deletions, inversions, translocations and inverted translocations on aligned genome segments. We also developed an MCMC algorithm to infer the order of the query segments. We proved that using any Euclidian metrics to measure distance between two sequence orders in the tree optimization goal function will lead to a degenerated solution where the inferred order will be the order of one of the leaf nodes. We also gave a graph-based formulation of the problem which can represent the probability distribution of the order of the query sequences.

This chapter describes the Multiple Carbohydrate Alignment with Weights (MCAW) tool, which is available as a part of the RINGS (Resource for INformatics of Glycomes at Soka) website. It implements a combination of KCaM (Aoki, Yamaguchi, Ueda, et al., Nucl Acids Res 32:W267-W272, 2004), a pairwise glycan alignment algorithm, and ClustalW (Thompson, Higgins, Gibson, Nucleic Acids Res 22:4673-80, 1994), a weighted multiple protein sequence alignment algorithm. This tool computes the multiple glycan alignment by first computing a guide tree to determine the order by which to progressively add glycans to the multiple alignment. The dynamic programming algorithm results in a glycan profile of the alignment glycans, containing "monosaccharide positions" indicating the ratio of monosaccharides and their glycosidic bonds that are aligned at the corresponding position. This tool has been used to analyze databases of glycan array experimental data, incorporating weights to reflect the biological significance of certain glycans over others. As a result, it has been shown that the alignments obtained are biologically relevant, matching the results as found in the literature.

Multiple alignment of biological sequences is an interesting area of research for application of parallel processing algorithms. For multiple alignment of sequences, parallelism can be introduced at different levels to reduce the overall time. This paper is concerned with the comparison of an MPI-based multiple sequence alignment algorithm by using single and multiple guide trees. In this work, we will look at the application of Divide-and-Conquer algorithm for multiple sequence alignment and discuss two different implementations on MPI. We compare the speed up of the two approaches and we contrast the quality of the alignments for these two approaches. These two approaches differ in using one single tree for alignment vs. multiple trees for alignment that we further discuss in this paper.

The alignment problem of DNA or protein sequences is very applicable and important in various fields of molecular biology. This problem can be reduced to the shortest path problem and Ikeda and Imai (Genome Informatics 5: 90-99, 1994) showed that the A(*) algorithm works efficiently with the estimator utilizing all 2-dimensional sub-alignments. In this paper we present new powerful estimators utilizing k >/= 3 dimensional sub-alignments, and propose a new bounding technique using V (Delta), a set of vertices in the paths whose lengths are at most Delta longer than the shortest path. We also extend our algorithm to a recursive-estimate version. These algorithms become more efficient when the number of sequences increase, or the similarity among sequences is lower.

Multiple protein sequence alignment using double-dynamic programming

Multiple protein sequence alignment using double-dynamic programming.

This article presents an immune inspired algorithm to tackle the Multiple Sequence Alignment (MSA) problem. MSA is one of the most important tasks in biological sequence analysis. Although this paper focuses on protein alignments, most of the discussion and methodology may also be applied to DNA alignments. The problem of finding the multiple alignment was investigated in the study by Bonizzoni and Vedova and Wang and Jiang, and proved to be a NP-hard (non-deterministic polynomial-time hard) problem. The presented algorithm, called Immunological Multiple Sequence Alignment Algorithm (IMSA), incorporates two new strategies to create the initial population and specific ad hoc mutation operators. It is based on the ‘weighted sum of pairs’ as objective function, to evaluate a given candidate alignment. IMSA was tested using both classical benchmarks of BAliBASE (versions 1.0, 2.0 and 3.0), and experimental results indicate that it is comparable with state-of-the-art multiple alignment algorithms, in terms of quality of alignments, weighted Sums-of-Pairs (SP) and Column Score (CS) values. The main novelty of IMSA is its ability to generate more than a single suboptimal alignment, for every MSA instance; this behaviour is due to the stochastic nature of the algorithm and of the populations evolved during the convergence process. This feature will help the decision maker to assess and select a biologically relevant multiple sequence alignment. Finally, the designed algorithm can be used as a local search procedure to properly explore promising alignments of the search space.

Multiple sequence alignment (MSA) plays a vital role in uncovering similarities among biological sequences such as DNA, RNA, or proteins, providing valuable information about their structural, functional, and evolutionary relationships. However, MSA is a computationally challenging problem, with complexity growing exponentially as the number and length of sequences increase. Currently, standard MSA tools like ClustalW, T-Coffee, and MAFFT, which are based on heuristic algorithms, are widely used but still face many challenges due to the combinatorial explosion. Recent advancements in MSA algorithms have employed reinforcement learning (RL), particularly deep reinforcement learning (DRL), and demonstrated optimized execution time and accuracy with promising results. This is because deep reinforcement learning algorithms update their search policies using gradient descent, instead of exploring the entire solution space making it significantly faster and efficient. In this article, we provide an overview of the recent historical advancements in MSA algorithms, highlighting RL models used to tackle the MSA problem and main challenges and opportunities in this regard.

Inverse parametric sequence alignment

Multiple sequence alignment involves alignment of more than two sequences and is an NP-complete problem. Therefore, heuristic algorithms that use different criteria to find an approximation to the optimal solution are employed. At the heart of these approaches lie the scoring and objective functions that a given algorithm uses to compare competing solutions in constructing a multiple sequence alignment. These objective functions are often motivated by the biological paradigms that govern functional similarities and evolutionary relations. Most existing approaches utilize a progressive process where the final alignment is constructed sequentially by adding new sequences into an existing multiple sequence alignment matrix, which is dynamically updated. In doing this, the core scoring function to assess accuracies of pairwise alignments generally remains the same, while the objective functions used in intermediary steps differ. Nevertheless, the overall assessment of the final multiple sequence alignment is generally calculated by an extension of pairwise scorings. In this chapter, we explore different scoring and objective functions used in calculating the accuracy and optimization of a multiple sequence alignment and provide utilization of these criteria in popularly used multiple sequence alignment algorithms.

Multiple sequence alignment (MSA) is a core problem in many applications. Various optimization algorithms such as genetic algorithm and particle swarm optimization (PSO) have been used to solve this problem, where all of them are adapted to work in the bioinformatics domain. This paper defines the MSA problem, suggests a novel MSA algorithm called ‘NestMSA’ and evaluates it in two domains: Web data extraction and removing different URLs with similar text (DUST). The suggested algorithm is inspired by the PSO optimization algorithm. It is not a generalization of a two-sequence alignment algorithm as it processes all the sequences at the same time. Therefore, it looks globally at the same time on all sequences. Different from other PSO-based alignment algorithms, swarm particles in the proposed NestMSA algorithm are nested inside the sequences and communicated together to align them. Therefore, global maximum is guaranteed in our algorithm. Furthermore, this work suggests a new objective function which both maximizes the number of matched characters and minimizes the number of gaps inserted in the sequences. The running time complexity and the efficiency of NestMSA are addressed in this paper. The experiments show an encouraging result as it outperforms the two approaches DCA and TEX in the Web data extraction domain (95% and 96% of recall and precision, respectively). Furthermore, it gives a high-performance result in the DUST domain (95%, 93% and 92% of recall, precision and SPS score, respectively).

T-Coffee (Tree-based consistency objective function for alignment evaluation) is a versatile multiple sequence alignment (MSA) method suitable for aligning most types of biological sequences. The main strength of T-Coffee is its ability to combine third party aligners and to integrate structural (or homology) information when building MSAs. The series of protocols presented here show how the package can be used to multiply align proteins, RNA and DNA sequences. The protein section shows how users can select the most suitable T-Coffee mode for their data set. Detailed protocols include T-Coffee, the default mode, M-Coffee, a meta version able to combine several third party aligners into one, PSI (position-specific iterated)-Coffee, the homology extended mode suitable for remote homologs and Expresso, the structure-based multiple aligner. We then also show how the T-RMSD (tree based on root mean square deviation) option can be used to produce a functionally informative structure-based clustering. RNA alignment procedures are described for using R-Coffee, a mode able to use predicted RNA secondary structures when aligning RNA sequences. DNA alignments are illustrated with Pro-Coffee, a multiple aligner specific of promoter regions. We also present some of the many reformatting utilities bundled with T-Coffee. The package is an open-source freeware available from http://www.tcoffee.org/.

We consider a branch-and-cut approach for solving the multiple sequence alignment problem, which is a central problem in computational biology. We propose a general model for this problem in which arbitrary gap costs are allowed. An interesting aspect of our approach is that the three (exponentially large) classes of natural valid inequalities that we consider turn out to be both facet-defining for the convex hull of integer solutions and separable in polynomial time. Both the proofs that these classes of valid inequalities are facet-defining and the description of the separation algorithms are far from trivial. Experimental results on several benchmark instances show that our method outperforms the best tools developed so far, in that it produces alignments that are better from a biological point of view. A noteworthy outcome of the results is the effectiveness of using branch-and-cut with only a carefully-selected subset of the variables as a heuristic.