Pairwise Alignment Algorithm Research Articles

Optimal gap-affine alignment in O(s) space.

Pairwise sequence alignment remains a fundamental problem in computational biology and bioinformatics. Recent advances in genomics and sequencing technologies demand faster and scalable algorithms that can cope with the ever-increasing sequence lengths. Classical pairwise alignment algorithms based on dynamic programming are strongly limited by quadratic requirements in time and memory. The recently proposed wavefront alignment algorithm (WFA) introduced an efficient algorithm to perform exact gap-affine alignment in O(ns) time, where s is the optimal score and n is the sequence length. Notwithstanding these bounds, WFA's O(s2) memory requirements become computationally impractical for genome-scale alignments, leading to a need for further improvement. In this article, we present the bidirectional WFA algorithm, the first gap-affine algorithm capable of computing optimal alignments in O(s) memory while retaining WFA's time complexity of O(ns). As a result, this work improves the lowest known memory bound O(n) to compute gap-affine alignments. In practice, our implementation never requires more than a few hundred MBs aligning noisy Oxford Nanopore Technologies reads up to 1 Mbp long while maintaining competitive execution times. All code is publicly available at https://github.com/smarco/BiWFA-paper. Supplementary data are available at Bioinformatics online.

End-to-end learning of multiple sequence alignments with differentiable Smith-Waterman.

Multiple sequence alignments (MSAs) of homologous sequences contain information on structural and functional constraints and their evolutionary histories. Despite their importance for many downstream tasks, such as structure prediction, MSA generation is often treated as a separate pre-processing step, without any guidance from the application it will be used for. Here, we implement a smooth and differentiable version of the Smith-Waterman pairwise alignment algorithm that enables jointly learning an MSA and a downstream machine learning system in an end-to-end fashion. To demonstrate its utility, we introduce SMURF (Smooth Markov Unaligned Random Field), a new method that jointly learns an alignment and the parameters of a Markov Random Field for unsupervised contact prediction. We find that SMURF learns MSAs that mildly improve contact prediction on a diverse set of protein and RNA families. As a proof of concept, we demonstrate that by connecting our differentiable alignment module to AlphaFold2 and maximizing predicted confidence, we can learn MSAs that improve structure predictions over the initial MSAs. Interestingly, the alignments that improve AlphaFold predictions are self-inconsistent and can be viewed as adversarial. This work highlights the potential of differentiable dynamic programming to improve neural network pipelines that rely on an alignment and the potential dangers of optimizing predictions of protein sequences with methods that are not fully understood. Our code and examples are available at: https://github.com/spetti/SMURF. Supplementary data are available at Bioinformatics online.

Pairwise Biological Network Alignment Based on Discrete Bat Algorithm.

The development of high-throughput technology has provided a reliable technical guarantee for an increased amount of available data on biological networks. Network alignment is used to analyze these data to identify conserved functional network modules and understand evolutionary relationships across species. Thus, an efficient computational network aligner is needed for network alignment. In this paper, the classic bat algorithm is discretized and applied to the network alignment. The bat algorithm initializes the population randomly and then searches for the optimal solution iteratively. Based on the bat algorithm, the global pairwise alignment algorithm BatAlign is proposed. In BatAlign, the individual velocity and the position are represented by a discrete code. BatAlign uses a search algorithm based on objective function that uses the number of conserved edges as the objective function. The similarity between the networks is used to initialize the population. The experimental results showed that the algorithm was able to match proteins with high functional consistency and reach a relatively high topological quality.

An accurate and exact clustering algorithm for next generation sequencing metagenomic sequences

Clustering algorithms are the essential tools in the target metagenomics, used to perform the taxonomic profiling of microbial communities. In the present study, an algorithmic tool called hash‐based exact alignment (HBEA) clustering algorithm is presented, which uses exact pairwise global alignment algorithm to improve the cluster quality and creates a hash table for extraction of cluster representatives. The algorithm is de novo based and uses the general de facto 97% sequence similarity score to cluster the sequences. Our experimental investigation on various types of datasets with distinct parameters and attributes showed that HBEA produces better operational taxonomic unit (OTU) clusters and computational complexity than other algorithms.

Pairwise Heuristic Sequence Alignment Algorithm Based on Deep Reinforcement Learning.

Goal: Various methods have been developed to analyze the association between organisms and their genomic sequences. Among them, sequence alignment is the most frequently used method for comparative analysis of biological genomes. We intend to propose a novel pairwise sequence alignment method using deep reinforcement learning to break out the old pairwise alignment algorithms. Methods: We defined the environment and agent to enable reinforcement learning in the sequence alignment system. This novel method, named DQNalign, can immediately determine the next direction by observing the subsequences within the moving window. Results: DQNalign shows superiority in the dissimilar sequence pairs that have low identity values. And theoretically, we confirm that DQNalign has a low dimension for the sequence length in view of the complexity. Conclusions: This research shows the application method of deep reinforcement learning to the sequence alignment system and how deep reinforcement learning can improve the conventional sequence alignment method.

SAlign\u2013a structure aware method for global PPI network alignment

BackgroundHigh throughput experiments have generated a significantly large amount of protein interaction data, which is being used to study protein networks. Studying complete protein networks can reveal more insight about healthy/disease states than studying proteins in isolation. Similarly, a comparative study of protein–protein interaction (PPI) networks of different species reveals important insights which may help in disease analysis and drug design. The study of PPI network alignment can also helps in understanding the different biological systems of different species. It can also be used in transfer of knowledge across different species. Different aligners have been introduced in the last decade but developing an accurate and scalable global alignment algorithm that can ensures the biological significance alignment is still challenging.ResultsThis paper presents a novel global pairwise network alignment algorithm, SAlign, which uses topological and biological information in the alignment process. The proposed algorithm incorporates sequence and structural information for computing biological scores, whereas previous algorithms only use sequence information. The alignment based on the proposed technique shows that the combined effect of structure and sequence results in significantly better pairwise alignments. We have compared SAlign with state-of-art algorithms on the basis of semantic similarity of alignment and the number of aligned nodes on multiple PPI network pairs. The results of SAlign on the network pairs which have high percentage of proteins with available structure are 3–63% semantically better than all existing techniques. Furthermore, it also aligns 5–14% more nodes of these network pairs as compared to existing aligners. The results of SAlign on other PPI network pairs are comparable or better than all existing techniques. We also introduce hbox {SAlign}^{mathrm{mc}}, a Monte Carlo based alignment algorithm, that produces multiple network alignments with similar semantic similarity. This helps the user to pick biologically meaningful alignments.ConclusionThe proposed algorithm has the ability to find the alignments that are more biologically significant/relevant as compared to the alignments of existing aligners. Furthermore, the proposed method is able to generate alternate alignments that help in studying different genes/proteins of the specie.

AligNet: alignment of protein-protein interaction networks

BackgroundAll molecular functions and biological processes are carried out by groups of proteins that interact with each other. Metaproteomic data continuously generates new proteins whose molecular functions and relations must be discovered. A widely accepted structure to model functional relations between proteins are protein-protein interaction networks (PPIN), and their analysis and alignment has become a key ingredient in the study and prediction of protein-protein interactions, protein function, and evolutionary conserved assembly pathways of protein complexes. Several PPIN aligners have been proposed, but attaining the right balance between network topology and biological information is one of the most difficult and key points in the design of any PPIN alignment algorithm.ResultsMotivated by the challenge of well-balanced and efficient algorithms, we have designed and implemented AligNet, a parameter-free pairwise PPIN alignment algorithm aimed at bridging the gap between topologically efficient and biologically meaningful matchings. A comparison of the results obtained with AligNet and with the best aligners shows that AligNet achieves indeed a good balance between topological and biological matching.ConclusionIn this paper we present AligNet, a new pairwise global PPIN aligner that produces biologically meaningful alignments, by achieving a good balance between structural matching and protein function conservation, and more efficient computations than state-of-the-art tools.

Fast gap-affine pairwise alignment using the wavefront algorithm.

MotivationPairwise alignment of sequences is a fundamental method in modern molecular biology, implemented within multiple bioinformatics tools and libraries. Current advances in sequencing technologies press for the development of faster pairwise alignment algorithms that can scale with increasing read lengths and production yields.ResultsIn this article, we present the wavefront alignment algorithm (WFA), an exact gap-affine algorithm that takes advantage of homologous regions between the sequences to accelerate the alignment process. As opposed to traditional dynamic programming algorithms that run in quadratic time, the WFA runs in time O(ns), proportional to the read length n and the alignment score s, using memory. Furthermore, our algorithm exhibits simple data dependencies that can be easily vectorized, even by the automatic features of modern compilers, for different architectures, without the need to adapt the code. We evaluate the performance of our algorithm, together with other state-of-the-art implementations. As a result, we demonstrate that the WFA runs 20–300× faster than other methods aligning short Illumina-like sequences, and 10–100× faster using long noisy reads like those produced by Oxford Nanopore Technologies.Availability and implementationThe WFA algorithm is implemented within the wavefront-aligner library, and it is publicly available at https://github.com/smarco/WFA.

PTM-MatAlign: A Fast GPU-based Algorithm for Pairwise Protein Structure Alignment

PTM-MatAlign: A Fast GPU-based Algorithm for Pairwise Protein Structure Alignment

LePrimAlign: local entropy-based alignment of PPI networks to predict conserved modules

BackgroundCross-species analysis of protein-protein interaction (PPI) networks provides an effective means of detecting conserved interaction patterns. Identifying such conserved substructures between PPI networks of different species increases our understanding of the principles deriving evolution of cellular organizations and their functions in a system level. In recent years, network alignment techniques have been applied to genome-scale PPI networks to predict evolutionary conserved modules. Although a wide variety of network alignment algorithms have been introduced, developing a scalable local network alignment algorithm with high accuracy is still challenging.ResultsWe present a novel pairwise local network alignment algorithm, called LePrimAlign, to predict conserved modules between PPI networks of three different species. The proposed algorithm exploits the results of a pairwise global alignment algorithm with many-to-many node mapping. It also applies the concept of graph entropy to detect initial cluster pairs from two networks. Finally, the initial clusters are expanded to increase the local alignment score that is formulated by a combination of intra-network and inter-network scores. The performance comparison with state-of-the-art approaches demonstrates that the proposed algorithm outperforms in terms of accuracy of identified protein complexes and quality of alignments.ConclusionThe proposed method produces local network alignment of higher accuracy in predicting conserved modules even with large biological networks at a reduced computational cost.

Design and Implementation of Pairwise Sequence Alignment Algorithm Components Based on Dynamic Programming

Design and Implementation of Pairwise Sequence Alignment Algorithm Components Based on Dynamic Programming

Pairwise alignment of nucleotide sequences using maximal exact matches

BackgroundPairwise alignment of short DNA sequences with affine-gap scoring is a common processing step performed in a range of bioinformatics analyses. Dynamic programming (i.e. Smith-Waterman algorithm) is widely used for this purpose. Despite using data level parallelisation, pairwise alignment consumes much time. There are faster alignment algorithms but they suffer from the lack of accuracy.ResultsIn this paper, we present MEM-Align, a fast semi-global alignment algorithm for short DNA sequences that allows for affine-gap scoring and exploit sequence similarity. In contrast to traditional alignment method (such as Smith-Waterman) where individual symbols are aligned, MEM-Align extracts Maximal Exact Matches (MEMs) using a bit-level parallel method and then looks for a subset of MEMs that forms the alignment using a novel dynamic programming method. MEM-Align tries to mimic alignment produced by Smith-Waterman. As a result, for 99.9% of input sequence pair, the computed alignment score is identical to the alignment score computed by Smith-Waterman. Yet MEM-Align is up to 14.5 times faster than the Smith-Waterman algorithm. Fast run-time is achieved by: (a) using a bit-level parallel method to extract MEMs; (b) processing MEMs rather than individual symbols; and, (c) applying heuristics.ConclusionsMEM-Align is a potential candidate to replace other pairwise alignment algorithms used in processes such as DNA read-mapping and Variant-Calling.

Antlion optimization algorithm for pairwise structural alignment with bi-objective functions

This research work concentrates on the pairwise protein structure alignment of numerous protein structures. This is considered to be a problematic job which is an NP-hard problem. This work proposed a bi-objective-based antlion optimization algorithm (BO-ALO) which is aimed to improve the geometrical and evolutionary relationship among the protein structures. The bi-objective functions are the RMSD and TM scores which aim to minimize the RMSD score and maximize the TM score. The BO-ALO method has been compared with various widespread existing methods such as SPalignNS, UniAlign, DALI, MICAN, GANGSTA, DeepAlign, TM-align, CE, ant colony optimization and artificial bee colony optimization methods. The experiments were taken from the benchmark datasets, namely SCOPe and CATH. Also, the predicted alignments were compared with gold standard benchmark databases such as CDD, MALIDUP, MALISAM and HOMSTRAD. The outcomes of the proposed method have better bi-objective function scores and performance measures than other well-known existing approaches. This work also evaluates the proposed method with its biological significance of predicting the common gene ontology functions among the aligned protein structures. Finally, the statistical significance of the BO-ALO is computed by employing the Wilcoxon matched-signed rank test. Also, the statistical significant results of the proposed methods give better results when compared to other existing approaches.

BGSA: a bit-parallel global sequence alignment toolkit for multi-core and many-core architectures

Modern bioinformatics tools for analyzing large-scale NGS datasets often need to include fast implementations of core sequence alignment algorithms in order to achieve reasonable execution times. We address this need by presenting the BGSA toolkit for optimized implementations of popular bit-parallel global pairwise alignment algorithms on modern microprocessors. BGSA outperforms Edlib, SeqAn and BitPAl for pairwise edit distance computations and Parasail, SeqAn and BitPAl when using more general scoring schemes for pairwise alignments of a batch of sequence reads on both standard multi-core CPUs and Xeon Phi many-core CPUs. Furthermore, banded edit distance performance of BGSA on a Xeon Phi-7210 outperforms the highly optimized NVBio implementation on a Titan X GPU for the seed verification stage of a read mapper by a factor of 4.4. BGSA is open-source and available at https://github.com/sdu-hpcl/BGSA. Supplementary data are available at Bioinformatics online.

A Simulation-Based Approach to Statistical Alignment.

Classic alignment algorithms utilize scoring functions which maximize similarity or minimize edit distances. These scoring functions account for both insertion-deletion (indel) and substitution events. In contrast, alignments based on stochastic models aim to explicitly describe the evolutionary dynamics of sequences by inferring relevant probabilistic parameters from input sequences. Despite advances in stochastic modeling during the last two decades, scoring-based methods are still dominant, partially due to slow running times of probabilistic approaches. Alignment inference using stochastic models involves estimating the probability of events, such as the insertion or deletion of a specific number of characters. In this work, we present SimBa-SAl, a simulation-based approach to statistical alignment inference, which relies on an explicit continuous time Markov model for both indels and substitutions. SimBa-SAl has several advantages. First, using simulations, it decouples the estimation of event probabilities from the inference stage, which allows the introduction of accelerations to the alignment inference procedure. Second, it is general and can accommodate various stochastic models of indel formation. Finally, it allows computing the maximum-likelihood alignment, the probability of a given pair of sequences integrated over all possible alignments, and sampling alternative alignments according to their probability. We first show that SimBa-SAl allows accurate estimation of parameters of the long-indel model previously developed by Miklós et al. (2004). We next show that SimBa-SAl is more accurate than previously developed pairwise alignment algorithms, when analyzing simulated as well as empirical data sets. Finally, we study the goodness-of-fit of the long-indel and TKF91 models. We show that although the long-indel model fits the data sets better than TKF91, there is still room for improvement concerning the realistic modeling of evolutionary sequence dynamics.

ASCA-PSO: Adaptive sine cosine optimization algorithm integrated with particle swarm for pairwise local sequence alignment

The sine cosine algorithm (SCA), a recently proposed population-based optimization algorithm, is based on the use of sine and cosine trigonometric functions as operators to update the movements of the search agents. To optimize performance, different parameters on the SCA must be appropriately tuned. Setting such parameters is challenging because they permit the algorithm to escape from local optima and avoid premature convergence. The main drawback of the SCA is that the parameter setting only affects the exploitation of the prominent regions. However, the SCA has good exploration capabilities. This article presents an enhanced version of the SCA by merging it with particle swarm optimization (PSO). PSO exploits the search space better than the operators of the standard SCA. The proposed algorithm, called ASCA-PSO, has been tested over several unimodal and multimodal benchmark functions, which show its superiority over the SCA and other recent and standard meta-heuristic algorithms. Moreover, to verify the capabilities of the SCA, the SCA has been used to solve the real-world problem of a pairwise local alignment algorithm that tends to find the longest consecutive substrings between two biological sequences. Experimental results provide evidence of the good performance of the ASCA-PSO solutions in terms of accuracy and computational time.

Parallelization of Pairwise Alignment and Neighbor-Joining Algorithm in Progressive Multiple Sequence Alignment

Progressive multiple sequence alignment ClustalW is a widely used heuristic method for computing multiple sequence alignment (MSA). It has three stages: distance matrix computation using pairwise alignment, guide tree reconstruction using neighbor-joining and progressive alignment. To accelerate computing for large data, the progressive MSA algorithm needs to be parallelized. This research aims to identify, decompose and implement the pairwise alignment and neighbor-joining in progressive MSA using message passing, shared memory and hybrid programming model in the computer cluster. The experimental results obtained shared memory programming model as the best scenario implementation with speed up up to 12 times.

Analyzing Glycan-Binding Profiles Using Weighted Multiple Alignment of Trees.

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.

CompPSA: A Component-Based Pairwise RNA Secondary Structure Alignment Algorithm

CompPSA: A Component-Based Pairwise RNA Secondary Structure Alignment Algorithm

Net2Align: An Algorithm For Pairwise Global Alignment of Biological Networks.

The amount of data on molecular interactions is growing at an enormous pace, whereas the progress of methods for analysing this data is still lacking behind. Particularly, in the area of comparative analysis of biological networks, where one wishes to explore the similarity between two biological networks, this holds a potential problem. In consideration that the functionality primarily runs at the network level, it advocates the need for robust comparison methods. In this paper, we describe Net2Align, an algorithm for pairwise global alignment that can perform node-to-node correspondences as well as edge-to-edge correspondences into consideration. The uniqueness of our algorithm is in the fact that it is also able to detect the type of interaction, which is essential in case of directed graphs. The existing algorithm is only able to identify the common nodes but not the common edges. Another striking feature of the algorithm is that it is able to remove duplicate entries in case of variable datasets being aligned. This is achieved through creation of a local database which helps exclude duplicate links. In a pervasive computational study on gene regulatory network, we establish that our algorithm surpasses its counterparts in its results. Net2Align has been implemented in Java 7 and the source code is available as supplementary files.