Multiple Sequence Alignment Algorithm Research Articles

FrameD: Framework for DNA-based Data Storage Design, Verification, and Validation.

DNA-based data storage is a quickly growing field that hopes to harness the massive theoretical information density of DNA molecules to produce a competitive next-generation storage medium suitable for archival data. In recent years, many DNA-based storage system designs have been proposed. Given that no common infrastructure exists for simulating these storage systems, comparing many different designs along with many different error models is increasingly difficult. To address this challenge we introduce FrameD, a simulation infrastructure for DNA storage systems that leverages the underlying modularity of DNA storage system designs to provide a framework to express different designs while being able to reuse common components. We demonstrate the utility of FrameD and the need for a common simulation platform using a case study. Our case study compares designs that utilize strand copies differently, some that align strand copies using Multiple Sequence Alignment (MSA) algorithms and others that do not. We found that the choice to include MSA in the pipeline is dependent on the error rate and the type of errors being injected and is not always beneficial. In addition to supporting a wide range of designs, FrameD provides the user with transparent parallelism to deal with a large number of reads from sequencing and the need for many fault injection iterations. We believe that FrameD fills a void in the tools publicly available to the DNA storage community by providing a modular and extensible framework with support for massive parallelism. As a result, it will help accelerate the design process of future DNA-based storage systems. The source code for FrameD along with the data generated during the demonstration of FrameD is available in a public Github repository at https://github.com/dna-storage/framed (10.5281/zenodo.7757762).

Leveraging protein language models for accurate multiple sequence alignments.

Multiple sequence alignment (MSA) is a critical step in the study of protein sequence and function. Typically, MSA algorithms progressively align pairs of sequences and combine these alignments with the aid of a guide tree. These alignment algorithms use scoring systems based on substitution matrices to measure amino acid similarities. Although successful, standard methods struggle on sets of proteins with low sequence identity: the so-called twilight zone of protein alignment. For these difficult cases, another source of information is needed. Protein language models are a powerful new approach that leverages massive sequence data sets to produce high-dimensional contextual embeddings for each amino acid in a sequence. These embeddings have been shown to reflect physicochemical and higher-order structural and functional attributes of amino acids within proteins. Here, we present a novel approach to MSA, based on clustering and ordering amino acid contextual embeddings. Our method for aligning semantically consistent groups of proteins circumvents the need for many standard components of MSA algorithms, avoiding initial guide tree construction, intermediate pairwise alignments, gap penalties, and substitution matrices. The added information from contextual embeddings leads to higher accuracy alignments for structurally similar proteins with low amino-acid similarity. We anticipate that protein language models will become a fundamental component of the next generation of algorithms for generating MSAs.

Study of the error correction capability of multiple sequence alignment algorithm (MAFFT) in DNA storage

Synchronization (insertions–deletions) errors are still a major challenge for reliable information retrieval in DNA storage. Unlike traditional error correction codes (ECC) that add redundancy in the stored information, multiple sequence alignment (MSA) solves this problem by searching the conserved subsequences. In this paper, we conduct a comprehensive simulation study on the error correction capability of a typical MSA algorithm, MAFFT. Our results reveal that its capability exhibits a phase transition when there are around 20% errors. Below this critical value, increasing sequencing depth can eventually allow it to approach complete recovery. Otherwise, its performance plateaus at some poor levels. Given a reasonable sequencing depth (≤ 70), MSA could achieve complete recovery in the low error regime, and effectively correct 90% of the errors in the medium error regime. In addition, MSA is robust to imperfect clustering. It could also be combined with other means such as ECC, repeated markers, or any other code constraints. Furthermore, by selecting an appropriate sequencing depth, this strategy could achieve an optimal trade-off between cost and reading speed. MSA could be a competitive alternative for future DNA storage.

Exploring Reinforcement Learning Methods for Multiple Sequence Alignment: A Brief Review

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.

PhenoTrack3D: an automatic high-throughput phenotyping pipeline to track maize organs over time.

High-throughput phenotyping platforms allow the study of the form and function of a large number of genotypes subjected to different growing conditions (GxE). A number of image acquisition and processing pipelines have been developed to automate this process, for micro-plots in the field and for individual plants in controlled conditions. Capturing shoot development requires extracting from images both the evolution of the 3D plant architecture as a whole, and a temporal tracking of the growth of its organs. We propose PhenoTrack3D, a new pipeline to extract a 3D + t reconstruction of maize. It allows the study of plant architecture and individual organ development over time during the entire growth cycle. The method tracks the development of each organ from a time-series of plants whose organs have already been segmented in 3D using existing methods, such as Phenomenal [Artzet et al. in BioRxiv 1:805739, 2019] which was chosen in this study. First, a novel stem detection method based on deep-learning is used to locate precisely the point of separation between ligulated and growing leaves. Second, a new and original multiple sequence alignment algorithm has been developed to perform the temporal tracking of ligulated leaves, which have a consistent geometry over time and an unambiguous topological position. Finally, growing leaves are back-tracked with a distance-based approach. This pipeline is validated on a challenging dataset of 60 maize hybrids imaged daily from emergence to maturity in the PhenoArch platform (ca. 250,000 images). Stem tip was precisely detected over time (RMSE < 2.1cm). 97.7% and 85.3% of ligulated and growing leaves respectively were assigned to the correct rank after tracking, on 30 plants × 43 dates. The pipeline allowed to extract various development and architecture traits at organ level, with good correlation to manual observations overall, on random subsets of 10-355 plants. We developed a novel phenotyping method based on sequence alignment and deep-learning. It allows to characterise the development of maize architecture at organ level, automatically and at a high-throughput. It has been validated on hundreds of plants during the entire development cycle, showing its applicability on GxE analyses of large maize datasets.

A Decomposition and Dominance-Based Multiobjective Artificial Bee Colony Algorithm for Multiple Sequence Alignment

The multiple sequence alignment (MSA) problem is essential in biological research for finding a specific relationship between the biologic sequences and their function. This study proposes a decomposition and dominance-based multiobjective artificial bee colony optimization algorithm for MSA (MOABC/D-MSA). MOABC/D-MSA uses three kinds of searching strategies to obtain a group of nondominated solutions with high quality and diversity of an MSA problem. A decomposition-based employed bee strategy is proposed to search for high-performance solutions of the MSA, while insuring their diversity. A nondominated sorting-based onlooker strategy searches for the solutions near the Pareto front (PF) to guide the subsequent searching. The scout bee strategy facilitates the algorithm to get out of the local optimal. A comparative experiment is implemented on BAliBASE 3.0, a benchmark for MSA algorithms. Experimental results show that the proposed algorithm has competitive performance with state-of-the-art metaheuristic algorithms. Furthermore, nondominated solutions of MOABC/D-MSA have a more uniform distribution in the objective space.

A novel fast multiple nucleotide sequence alignment method based on FM-index

Multiple sequence alignment (MSA) is fundamental to many biological applications. But most classical MSA algorithms are difficult to handle large-scale multiple sequences, especially long sequences. Therefore, some recent aligners adopt an efficient divide-and-conquer strategy to divide long sequences into several short sub-sequences. Selecting the common segments (i.e. anchors) for division of sequences is very critical as it directly affects the accuracy and time cost. So, we proposed a novel algorithm, FMAlign, to improve the performance of multiple nucleotide sequence alignment. We use FM-index to extract long common segments at a low cost rather than using a space-consuming hash table. Moreover, after finding the longer optimal common segments, the sequences are divided by the longer common segments. FMAlign has been tested on virus and bacteria genome and human mitochondrial genome datasets, and compared with existing MSA methods such as MAFFT, HAlign and FAME. The experiments show that our method outperforms the existing methods in terms of running time, and has a high accuracy on long sequence sets. All the results demonstrate that our method is applicable to the large-scale nucleotide sequences in terms of sequence length and sequence number. The source code and related data are accessible in https://github.com/iliuh/FMAlign.

A Greedy Clustering Algorithm for Multiple Sequence Alignment

This paper presents a strategy to tackle the Multiple Sequence Alignment (MSA) problem, which is one of the most important tasks in the biological sequence analysis. Its role is to align the sequences in their entirety to derive relationships and common characteristics between a set of protein or nucleotide sequences. The MSA problem was proved to be an NP-Hard problem. The proposed strategy incorporates a new idea based on the well-known divide and conquer paradigm. This paper presents a novel method of clustering sequences as a preliminary step to improve the final alignment; this decomposition can be used as an optimization procedure with any MSA aligner to explore promising alignments of the search space. In their solution, authors proposed to align the clusters in a parallel and distributed way in order to benefit from parallel architectures. The strategy was tested using classical benchmarks like BAliBASE, Sabre, Prefab4 and Oxm, and the experimental results show that it gives good results by comparing to the other aligners.

SNN-SB: Combining Partial Alignment Using Modified SNN Algorithm with Segment-Based for Multiple Sequence Alignments

Multiple sequence alignment (MSA) is an essential tool in the area of bioinformatics. Many MSA algorithms have been proposed last decade, however there is still opportunity for improvement in accuracy. Including partial alignment into MSA has been proved to be an effective approach to improve the quality of results of final Multiple sequence alignment. This paper presents a novel algorithm known as SNN-SB, which used to detect the related residue of protein sequences to build partial alignments using modified Shared Near Neighbors algorithm and segment-based alignments. The partial alignment is used as guide for DIALIGN-TX algorithm to build the final MSA. In order to evaluate the effectiveness of the SNN-SB, we compared the final result with 10 outstanding MSA tools. The results of SNN-SB got the maximum mean Q score and mean SP score on IRMBASE 2.0 benchmark. Moreover, it got around 8% improvement in BAliBASE 3.0 benchmark regarding to Q score compared to DIALIGN-TX.

A Greedy Clustering Algorithm for Multiple Sequence Alignment

This paper presents a strategy to tackle the Multiple Sequence Alignment (MSA) problem, which is one of the most important tasks in the biological sequence analysis. Its role is to align the sequences in their entirety to derive relationships and common characteristics between a set of protein or nucleotide sequences. The MSA problem was proved to be an NP-Hard problem. The proposed strategy incorporates a new idea based on the well-known divide and conquer paradigm. This paper presents a novel method of clustering sequences as a preliminary step to improve the final alignment; this decomposition can be used as an optimization procedure with any MSA aligner to explore promising alignments of the search space. In their solution, authors proposed to align the clusters in a parallel and distributed way in order to benefit from parallel architectures. The strategy was tested using classical benchmarks like BAliBASE, Sabre, Prefab4 and Oxm, and the experimental results show that it gives good results by comparing to the other aligners.

Efficient Multiple Sequences Alignment Algorithm Generation via Components Assembly Under PAR Framework.

As a key algorithm in bioinformatics, sequence alignment algorithm is widely used in sequence similarity analysis and genome sequence database search. Existing research focuses mainly on the specific steps of the algorithm or is for specific problems, lack of high-level abstract domain algorithm framework. Multiple sequence alignment algorithms are more complex, redundant, and difficult to understand, and it is not easy for users to select the appropriate algorithm; some computing errors may occur. Based on our constructed pairwise sequence alignment algorithm component library and the convenient software platform PAR, a few expansion domain components are developed for multiple sequence alignment application domain, and specific multiple sequence alignment algorithm can be designed, and its corresponding program, i.e., C++/Java/Python program, can be generated efficiently and thus enables the improvement of the development efficiency of complex algorithms, as well as accuracy of sequence alignment calculation. A star alignment algorithm is designed and generated to demonstrate the development process.

Benchmark of algorithms for multiple DNA sequence alignment across livestock species

Background: Due to the growing amount of biological data, it is often necessary to select the most optimal estimation method for DNA sequence alignment across livestock species. One of the most important benches of genomics is to modelling homology between considered DNA sequences. A multiple sequence alignment is a potent tool for molecular and evolutionary biology, and there are several programs and algorithms applicable for this purpose. The purpose of this paper was to study the most commonly used DNA alignment algorithms to select the optimal tool dedicated for short sequences.Methods: Four steps of bioinformatics pipelines were considered to benchmark the algorithms for multiple DNA sequence alignment across livestock species: 1) selection of reference genome sequences of ARS1.2 for cattle, EquCab3.0 for horse and vicPac2 for alpaca with a low E-value using TBLASTn 2) removing gaps for these sequences 3) alignment of obtained sequences using examined algorithms 4) matching the quality of aligned sequences with sequences of reference genomes by more software. The time of computation was archived for the whole analysis. The seven programs were utilized, each based on different alignment algorithms, namely: ClustalO, ClustalW, Kalign, MAFFT, MUSCLE, Probcons and T-Coffee.Results: The result obtained in this study showed that the fastest is progressive algorithms such as Kalign or MUSCLE-FAST. Moreover, the iterative algorithms like MAFFT and MUSCLE revealed a higher quality of the alignment. The T-Coffee and Probcons programs were computational cost-effective; simultaneously, they were generating a medium-quality calculation in a relatively long time. The best quality of alignment was shown by iterative variants of the MAFFT program; however, the speed of the calculations was relatively low. The fastest algorithm was Kalign, making alignment much faster than the competitors, but achieving average results in the quality of the alignment. The average speed ratio concerning the quality of the analyzed algorithms was obtained by the progressive version of MAFFT, NS1.Conclusions: We conclude that the results of this study can be used to re-alignment of variant primers in new livestock genome releases.

Multiple Alignment of Promoter Sequences from the Arabidopsis thaliana L. Genome.

In this study, we developed a new mathematical method for performing multiple alignment of highly divergent sequences (MAHDS), i.e., sequences that have on average more than 2.5 substitutions per position (x). We generated sets of artificial DNA sequences with x ranging from 0 to 4.4 and applied MAHDS as well as currently used multiple sequence alignment algorithms, including ClustalW, MAFFT, T-Coffee, Kalign, and Muscle to these sets. The results indicated that most of the existing methods could produce statistically significant alignments only for the sets with x < 2.5, whereas MAHDS could operate on sequences with x = 4.4. We also used MAHDS to analyze a set of promoter sequences from the Arabidopsis thaliana genome and discovered many conserved regions upstream of the transcription initiation site (from −499 to +1 bp); a part of the downstream region (from +1 to +70 bp) also significantly contributed to the obtained alignments. The possibilities of applying the newly developed method for the identification of promoter sequences in any genome are discussed. A server for multiple alignment of nucleotide sequences has been created.

Exact Multiple Sequence Alignment by Synchronized Decision Diagrams

This paper develops an exact solution algorithm for the multiple sequence alignment (MSA) problem. In the first step, we design a dynamic programming model and use it to construct a novel multivalued decision diagram (MDD) representation of all pairwise sequence alignments (PSA). PSA MDDs are then synchronized using side constraints to model the MSA problem as a mixed-integer program (MIP), for the first time, in polynomial space complexity. Two bound-based filtering procedures are developed to reduce the size of the MDDs, and the resulting MIP is solved using logic-based Benders decomposition. For a more effective algorithm, we develop a two-phase solution approach. In the first phase, we use optimistic filtering to quickly obtain a near-optimal bound, which we then use for exact filtering in the second phase to prove or obtain an optimal solution. Numerical results on benchmark instances show that our algorithm solves several instances to optimality for the first time, and, in case optimality cannot be proven, considerably improves upon a state-of-the-art heuristic MSA solver. Comparison with an existing state-of-the-art exact MSA algorithm shows that our approach is more time efficient and yields significantly smaller optimality gaps.

SpliVert: A Protein Multiple Sequence Alignment Refinement Method Based on Splitting-Splicing Vertically.

Multiple Sequence Alignment (MSA) is a fundamental task in bioinformatics and is required for many biological analysis tasks. The more accurate the alignments are, the more credible the downstream analyses. Most protein MSA algorithms realign an alignment to refine it by dividing it into two groups horizontally and then realign the two groups. However, this strategy does not consider that different regions of the sequences have different conservation; this property may lead to incorrect residue-residue or residue-gap pairs, which cannot be corrected by this strategy. In this article, our motivation is to develop a novel refinement method based on splitting- splicing vertically. Here, we present a novel refinement method based on splitting-splicing vertically, called SpliVert. For an alignment, we split it vertically into 3 parts, remove the gap characters in the middle, realign the middle part alone, and splice the realigned middle parts with the other two initial pieces to obtain a refined alignment. In the realign procedure of our method, the aligner will only focus on a certain part, ignoring the disturbance of the other parts, which could help fix the incorrect pairs. We tested our refinement strategy for 2 leading MSA tools on 3 standard benchmarks, according to the commonly used average SP (and TC) score. The results show that given appropriate proportions to split the initial alignment, the average scores are increased comparably or slightly after using our method. We also compared the alignments refined by our method with alignments directly refined by the original alignment tools. The results suggest that using our SpliVert method to refine alignments can also outperform direct use of the original alignment tools. The results reveal that splitting vertically and realigning part of the alignment is a good strategy for the refinement of protein multiple sequence alignments.

Component-Based Design and Assembly of Heuristic Multiple Sequence Alignment Algorithms.

In recent years, there has been an explosive increase in the amount of bioinformatics data produced, but data are not information. The purpose of bioinformatics research is to obtain information with biological significance from large amounts of data. Multiple sequence alignment is widely used in sequence homology detection, protein secondary and tertiary structure prediction, phylogenetic tree analysis, and other fields. Existing research mainly focuses on the specific steps of the algorithm or on specific problems, and there is a lack of high-level abstract domain algorithm frameworks. As a result, multiple sequence alignment algorithms are complex, redundant, and difficult to understand, and it is not easy for users to select the appropriate algorithm, which may lead to computing errors. Here, through in-depth study and analysis of the heuristic multiple sequence alignment algorithm (HMSAA) domain, a domain-feature model and an interactive model of HMSAA components have been established according to the generative programming method. With the support of the PAR (partition and recur) platform, the HMSAA algorithm component library is formalized and a specific alignment algorithm is assembled, thus improving the reliability of algorithm assembly. This work provides a valuable theoretical reference for the applications of other biological sequence analysis algorithms.

NestMSA: a new multiple sequence alignment algorithm

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).

Refin-Align: New Refinement Algorithm For Multiple Sequence Alignment

In this paper, we present Refin - Align a new refinement algorithm for a multiple sequence alignment . Refining alignment consists on constructing a new more accurate multiple sequence alignment from an initial one by applying some modifications. Our refinement algorithm Refin - Align uses a new definition of block and also our multiple sequence alignment algorithm Pro - malign . We assess our algorithm Refin - Align on multiple sequence alignment constructed by different algorithms using different benchmarks of protein sequences. In the most cases treated, our algorithm improves the scores of the multiple sequence alignment.

ProbPFP: a multiple sequence alignment algorithm combining hidden Markov model optimized by particle swarm optimization with partition function

BackgroundDuring procedures for conducting multiple sequence alignment, that is so essential to use the substitution score of pairwise alignment. To compute adaptive scores for alignment, researchers usually use Hidden Markov Model or probabilistic consistency methods such as partition function. Recent studies show that optimizing the parameters for hidden Markov model, as well as integrating hidden Markov model with partition function can raise the accuracy of alignment. The combination of partition function and optimized HMM, which could further improve the alignment’s accuracy, however, was ignored by these researches.ResultsA novel algorithm for MSA called ProbPFP is presented in this paper. It intergrate optimized HMM by particle swarm with partition function. The algorithm of PSO was applied to optimize HMM’s parameters. After that, the posterior probability obtained by the HMM was combined with the one obtained by partition function, and thus to calculate an integrated substitution score for alignment. In order to evaluate the effectiveness of ProbPFP, we compared it with 13 outstanding or classic MSA methods. The results demonstrate that the alignments obtained by ProbPFP got the maximum mean TC scores and mean SP scores on these two benchmark datasets: SABmark and OXBench, and it got the second highest mean TC scores and mean SP scores on the benchmark dataset BAliBASE. ProbPFP is also compared with 4 other outstanding methods, by reconstructing the phylogenetic trees for six protein families extracted from the database TreeFam, based on the alignments obtained by these 5 methods. The result indicates that the reference trees are closer to the phylogenetic trees reconstructed from the alignments obtained by ProbPFP than the other methods.ConclusionsWe propose a new multiple sequence alignment method combining optimized HMM and partition function in this paper. The performance validates this method could make a great improvement of the alignment’s accuracy.

Deoxyribonucleic Acid as a Tool for Digital Information Storage: An Overview

Current data storage technologies cannot keep pace longer with exponentially growing amounts of data through the extensive use of social networking photos and media, etc. The "digital world” with 4.4 zettabytes in 2013 has predicted it to reach 44 zettabytes by 2020. From the past 30 years, scientists and researchers have been trying to develop a robust way of storing data on a medium which is dense and ever-lasting and found DNA as the most promising storage medium. Unlike existing storage devices, DNA requires no maintenance, except the need to store at a cool and dark place. DNA has a small size with high density; just 1 gram of dry DNA can store about 455 exabytes of data. DNA stores the informations using four bases, viz., A, T, G, and C, while CDs, hard disks and other devices stores the information using 0’s and 1’s on the spiral tracks. In the DNA based storage, after binarization of digital file into the binary codes, encoding and decoding are important steps in DNA based storage system. Once the digital file is encoded, the next step is to synthesize arbitrary single-strand DNA sequences and that can be stored in the deep freeze until use.When there is a need for information to be recovered, it can be done using DNA sequencing. New generation sequencing (NGS) capable of producing sequences with very high throughput at a much lower cost about less than 0.1 USD for one MB of data than the first sequencing technologies. Post-sequencing processing includes alignment of all reads using multiple sequence alignment (MSA) algorithms to obtain different consensus sequences. The consensus sequence is decoded as the reversal of the encoding process. Most prior DNA data storage efforts sequenced and decoded the entire amount of stored digital information with no random access, but nowadays it has become possible to extract selective files (e.g., retrieving only required image from a collection) from a DNA pool using PCR-based random access. Various scientists successfully stored up to 110 zettabytes data in one gram of DNA. In the future, with an efficient encoding, error corrections, cheaper DNA synthesis,and sequencing, DNA based storage will become a practical solution for storage of exponentially growing digital data.