{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T20:04:25Z","timestamp":1770494665876,"version":"3.49.0"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1011988","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000}}],"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 62131004"],"award-info":[{"award-number":["No. 62131004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 62271353"],"award-info":[{"award-number":["No. 62271353"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2022ZD0117700"],"award-info":[{"award-number":["2022ZD0117700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LD24F020004"],"award-info":[{"award-number":["LD24F020004"]}]},{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["2022NSFSC0926"],"award-info":[{"award-number":["2022NSFSC0926"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Municipal Government of Quzhou","award":["No. 2023D036"],"award-info":[{"award-number":["No. 2023D036"]}]},{"name":"Fellowship of China Postdoctoral Science Foundation","award":["2023M731984,GZB20230365"],"award-info":[{"award-number":["2023M731984,GZB20230365"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Accurate multiple sequence alignment (MSA) is imperative for the comprehensive analysis of biological sequences. However, a notable challenge arises as no single MSA tool consistently outperforms its counterparts across diverse datasets. Users often have to try multiple MSA tools to achieve optimal alignment results, which can be time-consuming and memory-intensive. While the overall accuracy of certain MSA results may be lower, there could be local regions with the highest alignment scores, prompting researchers to seek a tool capable of merging these locally optimal results from multiple initial alignments into a globally optimal alignment. In this study, we introduce Two Pointers Meta-Alignment (TPMA), a novel tool designed for the integration of nucleic acid sequence alignments. TPMA employs two pointers to partition the initial alignments into blocks containing identical sequence fragments. It selects blocks with the high sum of pairs (SP) scores to concatenate them into an alignment with an overall SP score superior to that of the initial alignments. Through tests on simulated and real datasets, the experimental results consistently demonstrate that TPMA outperforms M-Coffee in terms of aSP, Q, and total column (TC) scores across most datasets. Even in cases where TPMA\u2019s scores are comparable to M-Coffee, TPMA exhibits significantly lower running time and memory consumption. Furthermore, we comprehensively assessed all the MSA tools used in the experiments, considering accuracy, time, and memory consumption. We propose accurate and fast combination strategies for small and large datasets, which streamline the user tool selection process and facilitate large-scale dataset integration. The dataset and source code of TPMA are available on GitHub (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/github.com\/malabz\/TPMA\" xlink:type=\"simple\">https:\/\/github.com\/malabz\/TPMA<\/jats:ext-link>).<\/jats:p>","DOI":"10.1371\/journal.pcbi.1011988","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T17:49:47Z","timestamp":1711993787000},"page":"e1011988","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["TPMA: A two pointers meta-alignment tool to ensemble different multiple nucleic acid sequence alignments"],"prefix":"10.1371","volume":"20","author":[{"given":"Yixiao","family":"Zhai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiannan","family":"Chao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yizheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1788-3084","authenticated-orcid":true,"given":"Pinglu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Furong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6406-1142","authenticated-orcid":true,"given":"Quan","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,4,1]]},"reference":[{"issue":"4","key":"pcbi.1011988.ref001","doi-asserted-by":"crossref","first-page":"546","DOI":"10.3390\/biom12040546","article-title":"Developments in algorithms for sequence alignment: a review.","volume":"12","author":"J Chao","year":"2022","journal-title":"Biomolecules"},{"issue":"4","key":"pcbi.1011988.ref002","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT multiple sequence alignment software version 7: improvements in performance and usability","volume":"30","author":"K Katoh","year":"2013","journal-title":"Mol Biol Evol"},{"issue":"5","key":"pcbi.1011988.ref003","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1093\/nar\/gkh340","article-title":"MUSCLE: multiple sequence alignment with high accuracy and high throughput","volume":"32","author":"RC Edgar","year":"2004","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"pcbi.1011988.ref004","doi-asserted-by":"crossref","DOI":"10.31449\/inf.v43i4.2621","article-title":"Refin-Align: New Refinement Algorithm for Multiple Sequence Alignment.","volume":"43","author":"A Mokaddem","year":"2019","journal-title":"Informatica"},{"issue":"9","key":"pcbi.1011988.ref005","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1093\/nar\/gkl274","article-title":"Refining multiple sequence alignments with conserved core regions","volume":"34","author":"S Chakrabarti","year":"2006","journal-title":"Nucleic Acids Res"},{"issue":"8","key":"pcbi.1011988.ref006","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1093\/bioinformatics\/bti159","article-title":"Evaluation of iterative alignment algorithms for multiple alignment","volume":"21","author":"IM Wallace","year":"2005","journal-title":"Bioinformatics"},{"key":"pcbi.1011988.ref007","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2105-15-265","article-title":"ReformAlign: improved multiple sequence alignments using a profile-based meta-alignment approach.","volume":"15","author":"DP Lyras","year":"2014","journal-title":"BMC Bioinform"},{"issue":"2","key":"pcbi.1011988.ref008","first-page":"122","article-title":"Combining many multiple alignments in one improved alignment","volume":"15","author":"K Bucka-Lassen","year":"1999","journal-title":"Bioinformatics (Oxford, England)."},{"key":"pcbi.1011988.ref009","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2105-13-117","article-title":"MergeAlign: improving multiple sequence alignment performance by dynamic reconstruction of consensus multiple sequence alignments.","volume":"13","author":"PW Collingridge","year":"2012","journal-title":"BMC Bioinform"},{"issue":"2","key":"pcbi.1011988.ref010","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/bioinformatics\/btp651","article-title":"AQUA: automated quality improvement for multiple sequence alignments","volume":"26","author":"J Muller","year":"2010","journal-title":"Bioinformatics"},{"issue":"9","key":"pcbi.1011988.ref011","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1093\/bioinformatics\/btg133","article-title":"RASCAL: rapid scanning and correction of multiple sequence alignments","volume":"19","author":"JD Thompson","year":"2003","journal-title":"Bioinformatics"},{"issue":"6","key":"pcbi.1011988.ref012","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1093\/nar\/gkl091","article-title":"M-Coffee: combining multiple sequence alignment methods with T-Coffee","volume":"34","author":"IM Wallace","year":"2006","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pcbi.1011988.ref013","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1748-7188-3-6","article-title":"DIALIGN-TX: greedy and progressive approaches for segment-based multiple sequence alignment","volume":"3","author":"AR Subramanian","year":"2008","journal-title":"Algorithms Mol Biol"},{"issue":"1","key":"pcbi.1011988.ref014","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1006\/jmbi.2000.4042","article-title":"T-Coffee: A novel method for fast and accurate multiple sequence alignment","volume":"302","author":"C Notredame","year":"2000","journal-title":"J Mol Biol"},{"issue":"10a","key":"pcbi.1011988.ref015","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1101\/gr.2286304","article-title":"Mitochondrial genome variation in eastern Asia and the peopling of Japan","volume":"14","author":"M Tanaka","year":"2004","journal-title":"Genome Res"},{"issue":"6155","key":"pcbi.1011988.ref016","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1126\/science.1241844","article-title":"Ancient DNA reveals key stages in the formation of central European mitochondrial genetic diversity","volume":"342","author":"G Brandt","year":"2013","journal-title":"Science"},{"issue":"suppl_2","key":"pcbi.1011988.ref017","doi-asserted-by":"crossref","first-page":"W394","DOI":"10.1093\/nar\/gkl244","article-title":"NAST: a multiple sequence alignment server for comparative analysis of 16S rRNA genes","volume":"34","author":"TZ DeSantis","year":"2006","journal-title":"Nucleic Acids Res"},{"issue":"22","key":"pcbi.1011988.ref018","doi-asserted-by":"crossref","first-page":"5019","DOI":"10.1093\/bioinformatics\/btac658","article-title":"WMSA: a novel method for multiple sequence alignment of DNA sequences","volume":"38","author":"Y Wei","year":"2022","journal-title":"Bioinformatics"},{"issue":"8","key":"pcbi.1011988.ref019","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1093\/molbev\/msp098","article-title":"INDELible: a flexible simulator of biological sequence evolution","volume":"26","author":"W Fletcher","year":"2009","journal-title":"Mol Biol Evol"},{"issue":"5","key":"pcbi.1011988.ref020","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1093\/molbev\/msaa015","article-title":"IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era","volume":"37","author":"BQ Minh","year":"2020","journal-title":"Mol Biol Evol"},{"issue":"21","key":"pcbi.1011988.ref021","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal W and Clustal X version 2.0","volume":"23","author":"MA Larkin","year":"2007","journal-title":"Bioinformatics"},{"issue":"8","key":"pcbi.1011988.ref022","doi-asserted-by":"crossref","first-page":"msac166","DOI":"10.1093\/molbev\/msac166","article-title":"HAlign 3: fast multiple alignment of ultra-large numbers of similar DNA\/RNA sequences","volume":"39","author":"F Tang","year":"2022","journal-title":"Mol Biol Evol"},{"issue":"6","key":"pcbi.1011988.ref023","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1093\/bioinformatics\/btz795","article-title":"Kalign 3: multiple sequence alignment of large datasets.","volume":"36","author":"T Lassmann","year":"2019","journal-title":"Bioinformatics"},{"issue":"1","key":"pcbi.1011988.ref024","doi-asserted-by":"crossref","first-page":"6968","DOI":"10.1038\/s41467-022-34630-w","article-title":"Muscle5: High-accuracy alignment ensembles enable unbiased assessments of sequence homology and phylogeny.","volume":"13","author":"RC Edgar","year":"2022","journal-title":"Nat Commun"},{"issue":"3","key":"pcbi.1011988.ref025","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1093\/bioinformatics\/btg008","article-title":"PCMA: fast and accurate multiple sequence alignment based on profile consistency","volume":"19","author":"J Pei","year":"2003","journal-title":"Bioinformatics"},{"issue":"3","key":"pcbi.1011988.ref026","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1093\/bioinformatics\/18.3.452","article-title":"Multiple sequence alignment using partial order graphs","volume":"18","author":"C Lee","year":"2002","journal-title":"Bioinformatics"},{"key":"pcbi.1011988.ref027","doi-asserted-by":"crossref","first-page":"bbad190","DOI":"10.1093\/bib\/bbad190","article-title":"WMSA 2: a multiple DNA\/RNA sequence alignment tool implemented with accurate progressive mode and a fast win-win mode combining the center star and progressive strategies.","author":"J Chen","year":"2023","journal-title":"Brief Bioinformatics"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1011988","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011988","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T20:22:53Z","timestamp":1712866973000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011988"}},"subtitle":[],"editor":[{"given":"Xin","family":"Gao","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,4,1]]},"references-count":27,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1011988","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pcbi.1011988","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,1]]}}}