<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.4 20241031//EN"
        "https://jats.nlm.nih.gov/publishing/1.4/JATS-journalpublishing1-4.dtd">
<article  article-type="research-article"        dtd-version="1.4">
            <front>

                <journal-meta>
                                                                <journal-id>gummfd</journal-id>
            <journal-title-group>
                                                                                    <journal-title>Gazi Üniversitesi Mühendislik Mimarlık Fakültesi Dergisi</journal-title>
            </journal-title-group>
                            <issn pub-type="ppub">1300-1884</issn>
                                        <issn pub-type="epub">1304-4915</issn>
                                                                                            <publisher>
                    <publisher-name>Gazi Üniversitesi</publisher-name>
                </publisher>
                    </journal-meta>
                <article-meta>
                                        <article-id pub-id-type="doi">10.17341/gazimmfd.1610635</article-id>
                                                                <article-categories>
                                            <subj-group  xml:lang="en">
                                                            <subject>Data Structures and Algorithms</subject>
                                                            <subject>Informetrics</subject>
                                                    </subj-group>
                                            <subj-group  xml:lang="tr">
                                                            <subject>Veri Yapıları ve Algoritmalar</subject>
                                                            <subject>İnformetrik</subject>
                                                    </subj-group>
                                    </article-categories>
                                                                                                                                                        <title-group>
                                                                                                                        <article-title>DNA dizileri için sezgisel yöntemlere dayalı çoklu dizi hizalama yaklaşımlarının karşılaştırılması</article-title>
                                                                                                                                                                                                <trans-title-group xml:lang="en">
                                    <trans-title>Comparison of multiple sequence alignment approaches based on heuristic methods for DNA sequences</trans-title>
                                </trans-title-group>
                                                                                                    </title-group>
            
                                                    <contrib-group content-type="authors">
                                                                        <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0002-5816-4804</contrib-id>
                                                                <name>
                                    <surname>Erdirik</surname>
                                    <given-names>Hatice</given-names>
                                </name>
                                                                    <aff>YILDIZ TECHNICAL UNIVERSITY</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0002-0907-751X</contrib-id>
                                                                <name>
                                    <surname>Karcıoğlu</surname>
                                    <given-names>Abdullah Ammar</given-names>
                                </name>
                                                                    <aff>ATATÜRK ÜNİVERSİTESİ, MÜHENDİSLİK FAKÜLTESİ</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0002-4368-0988</contrib-id>
                                                                <name>
                                    <surname>Tanyolaç</surname>
                                    <given-names>Bahattin</given-names>
                                </name>
                                                                    <aff>EGE ÜNİVERSİTESİ</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0002-4872-5698</contrib-id>
                                                                <name>
                                    <surname>Bulut</surname>
                                    <given-names>Hasan</given-names>
                                </name>
                                                                    <aff>EGE ÜNİVERSİTESİ</aff>
                                                            </contrib>
                                                                                </contrib-group>
                        
                                        <pub-date pub-type="pub" iso-8601-date="20260331">
                    <day>03</day>
                    <month>31</month>
                    <year>2026</year>
                </pub-date>
                                        <volume>41</volume>
                                        <issue>1</issue>
                                        <fpage>479</fpage>
                                        <lpage>494</lpage>
                        
                        <history>
                                    <date date-type="received" iso-8601-date="20241231">
                        <day>12</day>
                        <month>31</month>
                        <year>2024</year>
                    </date>
                                                    <date date-type="accepted" iso-8601-date="20260106">
                        <day>01</day>
                        <month>06</month>
                        <year>2026</year>
                    </date>
                            </history>
                                        <permissions>
                    <copyright-statement>Copyright © 1986, Gazi Üniversitesi Mühendislik Mimarlık Fakültesi Dergisi</copyright-statement>
                    <copyright-year>1986</copyright-year>
                    <copyright-holder>Gazi Üniversitesi Mühendislik Mimarlık Fakültesi Dergisi</copyright-holder>
                </permissions>
            
                                                                                                <abstract><p>Biyoenformatik, biyolojik verileri kavramsallaştırmak ve aralarındaki ilişkileri anlamak için matematik, bilgi işlem ve istatistikten faydalanan bir bilim dalıdır. Artan biyolojik veri hacmi, dizi hizalama problemini daha karmaşık hale getirerek manuel çözümleri imkânsız kılmıştır. Bu nedenle, otomatik hesaplama sistemleri geliştirilmiştir. Dizi hizalaması, çiftli ve çoklu olmak üzere iki kategoriye ayrılır. Bu çalışma, genetik algoritma (GA), diferansiyel evrim (DE) ve simüle edilmiş tavlama (SA) algoritmaları gibi meta-sezgisel yöntemleri kullanarak çoklu dizi hizalama problemine odaklanmaktadır. GA, DE, GASA ve DESA algoritmaları önerilmiş ve DNA dizileri üzerinde Needleman-Wunsch algoritmasıyla hizalamalar yapılmıştır. Deneyler, GA&#039;nın en iyi çalışma zamanına sahip olduğunu, DE ve DESA&#039;nın ise daha uzun sürdüğünü göstermiştir. GA, DE ve DESA, GASA&#039;ya göre daha yüksek hizalama puanları üretmiştir. Önerilen algoritmalar, Clustal algoritmasına kıyasla çoğu veri kümesinde daha iyi hizalama puanları sunarken, Clustal en hızlı çalışmayı gerçekleştirmiştir. Ayrıca, önerilen yöntemlerin aynı uzunluktaki diziler üzerinde mevcut algoritmalardan üstün performans gösterdiği tespit edilmiştir. Özellikle dört veri kümesinde (trnN-GUU_rps12, rrn4.5_rps12, rrn5_rps12, psbT_pbf1) önerilen algoritmalar daha yüksek puanlar elde etmiştir.</p></abstract>
                                                                                                                                    <trans-abstract xml:lang="en">
                            <p>Bioinformatics utilizes mathematics, computing, and statistics to analyze biological data and establish relationships among them. As biological data volumes increase, the sequence alignment problem becomes more complex, rendering manual solutions impractical and necessitating automated computational systems. Sequence alignment is categorized into pairwise and multiple sequence alignment. This study addresses the multiple sequence alignment problem using meta-heuristic approaches, specifically genetic algorithms (GA), differential evolution (DE), and simulated annealing (SA). Four algorithmic variations—GA, DE, GASA, and DESA—are proposed, reordering DNA sequences with the Needleman-Wunsch algorithm to produce diverse alignments. Experimental results show that GA, DE, and DESA achieved higher alignment scores than GASA, with GA exhibiting the fastest runtime, while DE and DESA had longer runtimes than both GA and GASA. Compared to the Clustal algorithm, the proposed algorithms generally achieved better alignment scores across most datasets, though Clustal demonstrated the fastest runtime. Specifically, for four datasets (trnN-GUU_rps12, rrn4.5_rps12, rrn5_rps12, psbT_pbf1), the proposed algorithms outperformed Clustal in alignment scores. Additionally, the proposed methods proved more effective on datasets with sequences of equal length compared to existing alignment algorithms. These findings highlight the potential of the proposed algorithms in improving multiple sequence alignment outcomes.</p></trans-abstract>
                                                            
            
                                                            <kwd-group>
                                                    <kwd>Çoklu Dizi Hizalaması</kwd>
                                                    <kwd>  Sezgisel Yaklaşım</kwd>
                                                    <kwd>  Genetik Algoritma</kwd>
                                                    <kwd>  Diferansiyel Evrim</kwd>
                                                    <kwd>  Benzetimli Tavlama</kwd>
                                                    <kwd>  Biyoenformatik.</kwd>
                                            </kwd-group>
                                                        
                                                                            <kwd-group xml:lang="en">
                                                    <kwd>Multiple Sequence Alignmnet</kwd>
                                                    <kwd>  Heuristic Approach</kwd>
                                                    <kwd>  Genetic Algorithm</kwd>
                                                    <kwd>  Differential Evaluation</kwd>
                                                    <kwd>  Simulated Annealing</kwd>
                                                    <kwd>  Bioinformatic</kwd>
                                            </kwd-group>
                                                                                                        <funding-group specific-use="FundRef">
                    <award-group>
                                                    <funding-source>
                                <named-content content-type="funder_name">Ege Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü</named-content>
                            </funding-source>
                                                                            <award-id>FOA-2020-20981</award-id>
                                            </award-group>
                </funding-group>
                                </article-meta>
    </front>
    <back>
                            <ref-list>
                                    <ref id="ref1">
                        <label>1</label>
                        <mixed-citation publication-type="journal">1.	Cohen, J., Bioinformatics-an introduction for computer scientists, ACM Comput. Surv. ,36 (2), 122-158, 2004.</mixed-citation>
                    </ref>
                                    <ref id="ref2">
                        <label>2</label>
                        <mixed-citation publication-type="journal">2.	Luscombe N.M., Greenbaum D., Gerstein M., What is bioinformatics? An introduction and overview, Yearbook of medical informatics, 10 (1), 83-100, 2001.</mixed-citation>
                    </ref>
                                    <ref id="ref3">
                        <label>3</label>
                        <mixed-citation publication-type="journal">3.	Karcioglu A.A., Bulut H., Improving hash-q exact string-matching algorithm with perfect hashing for DNA sequences, Computers in Biology and Medicine,131, 104292, 2021.</mixed-citation>
                    </ref>
                                    <ref id="ref4">
                        <label>4</label>
                        <mixed-citation publication-type="journal">4.	Karcıoğlu A.A, Bulut H., Q-gram hash comparison based multiple exact string matching algorithm for DNA sequences, Journal of the Faculty of Engineering and Architecture of Gazi University, 38 (2), 2023.</mixed-citation>
                    </ref>
                                    <ref id="ref5">
                        <label>5</label>
                        <mixed-citation publication-type="journal">5.	Karcioglu A.A., Bulut H., The WM-q multiple exact string matching algorithm for DNA sequences, Computers in Biology and Medicine, 136, 104656, 2021.</mixed-citation>
                    </ref>
                                    <ref id="ref6">
                        <label>6</label>
                        <mixed-citation publication-type="journal">6.	Karcioglu A.A., Bulut H., q-frame hash comparison based exact string matching algorithms for DNA sequences, Concurrency and Computation: Practice and Experience, 34 (9), 2022.</mixed-citation>
                    </ref>
                                    <ref id="ref7">
                        <label>7</label>
                        <mixed-citation publication-type="journal">7.	Botta M., Negro G., Multiple sequence alignment with genetic algorithms, Computational Intelligence Methods for Bioinformatics and Biostatistics, Springer, Berlin, Germany, 206-214, 2009.</mixed-citation>
                    </ref>
                                    <ref id="ref8">
                        <label>8</label>
                        <mixed-citation publication-type="journal">8.	Haque W., Aravind A., Reddy B., Pairwise sequence alignment algorithms: a survey, Information Science, Technology and Applications Conference, 96-103, 2009.</mixed-citation>
                    </ref>
                                    <ref id="ref9">
                        <label>9</label>
                        <mixed-citation publication-type="journal">9.	Lee Z.J., Su S.F., Chuang C.C., Liu K.H., Genetic algorithm with ant colony optimization (GA-ACO) for multiple sequence alignment, Applied Soft Computing, 8 (1), 55-78, 2008.</mixed-citation>
                    </ref>
                                    <ref id="ref10">
                        <label>10</label>
                        <mixed-citation publication-type="journal">10.	Zhu X., Li K., Salah A., A data parallel strategy for aligning multiple biological sequences on multi-core computers, Computers in biology and medicine, 43 (4), 350-361, 2013.</mixed-citation>
                    </ref>
                                    <ref id="ref11">
                        <label>11</label>
                        <mixed-citation publication-type="journal">11.	Liu X., Yang X., Wang C., Yao Y., Dai Q., Number of distinct sequence alignments with k-match and match sections, Computers in biology and medicine, 63, 287-292, 2015.</mixed-citation>
                    </ref>
                                    <ref id="ref12">
                        <label>12</label>
                        <mixed-citation publication-type="journal">12.	Naorem L. D., Sharma N., Raghava G. P., A web server for predicting and scanning of IL-5 inducing peptides using alignment-free and alignment-based method,Computers in Biology and Medicine, 158, 106864, 2023.</mixed-citation>
                    </ref>
                                    <ref id="ref13">
                        <label>13</label>
                        <mixed-citation publication-type="journal">13.	Pais F.S.M., Ruy P.D.C., Oliveira G., Coimbra R.S., Assessing the efficiency of multiple sequence alignment programs, Algorithms for Molecular Biology, 9 (1), 4, 2014.</mixed-citation>
                    </ref>
                                    <ref id="ref14">
                        <label>14</label>
                        <mixed-citation publication-type="journal">14.	Aktan M.N., Bulut H., Metaheuristic task scheduling algorithms for cloud computing environments, Concurrency and Computation: Practice and Experience, 34 (9), 2022.</mixed-citation>
                    </ref>
                                    <ref id="ref15">
                        <label>15</label>
                        <mixed-citation publication-type="journal">15.	Çavga S. H., Performance of neural networks and heuristic models for disease prediction from liver enzymes: Application to biochemistry device output, Journal of the Faculty of Engineering and Architecture of Gazi University, 39 (4), 2263-2270, 2024</mixed-citation>
                    </ref>
                                    <ref id="ref16">
                        <label>16</label>
                        <mixed-citation publication-type="journal">16.	Kaya F., Conker Ç., Hybrid input shaper design and genetic algorithm-based multi-objective optimization for elimination of residual vibrations at specific frequencies in flexible systems, Journal of the Faculty of Engineering and Architecture of Gazi University (Advanced Online Publication), 2541-2552, 2025.</mixed-citation>
                    </ref>
                                    <ref id="ref17">
                        <label>17</label>
                        <mixed-citation publication-type="journal">17.	Arıkan M., Hybrid simulated annealing–tabu search algorithms for solving U-shaped type-2 assembly line balancing problems with workload smoothing objective, Journal of the Faculty of Engineering and Architecture of Gazi University, 39 (3), 1457–1472, 2024.</mixed-citation>
                    </ref>
                                    <ref id="ref18">
                        <label>18</label>
                        <mixed-citation publication-type="journal">18.	Yalcin A., Deliktas D., Genetic algorithm based on weighted goal programming for doctor rostering problem, Journal of the Faculty of Engıneerıng and Archıtecture of Gazı Unıversıty, 39 (4), 2567-2585, 2024.</mixed-citation>
                    </ref>
                                    <ref id="ref19">
                        <label>19</label>
                        <mixed-citation publication-type="journal">19.	Erdirik H., Karcıoğlu A. A., Tanyolaç B., Bulut H., Meta-Sezgisel Tabanlı Clustal-SA Algoritmasını Kullanarak DNA Sekanslarında Çoklu Dizi Hizalama, Journal of the Institute of Science and Technology, 14 (2), 544-562, 2024.</mixed-citation>
                    </ref>
                                    <ref id="ref20">
                        <label>20</label>
                        <mixed-citation publication-type="journal">20.	Bucak, İ. Ö., Uslan, V., Sequence alignment from the perspective of stochastic optimization: a Survey, Turkish Journal of Electrical Engineering and Computer Sciences, 19 (1), 157-173, 2011.</mixed-citation>
                    </ref>
                                    <ref id="ref21">
                        <label>21</label>
                        <mixed-citation publication-type="journal">21.	Nalbantoğlu O.U., Dynamic Programming, Multiple Sequence Alignment Methods, Methods in Molecular Biology, 1079, Russell D.J., Springer, 3–27, 2014.</mixed-citation>
                    </ref>
                                    <ref id="ref22">
                        <label>22</label>
                        <mixed-citation publication-type="journal">22.	Karadimitriou K., Kraft D.H., Genetic algorithms and the multiple sequence alignment problem in biology, Second Annual Molecular Biology and Biotechnology Conference, Baton Rouge, 1–7, 1996.</mixed-citation>
                    </ref>
                                    <ref id="ref23">
                        <label>23</label>
                        <mixed-citation publication-type="journal">23.	Onwubolu G., Davendra D., Scheduling flow shops using differential evolution algorithm, European Journal of Operational Research, 171 (2), 674-692, 2006.</mixed-citation>
                    </ref>
                                    <ref id="ref24">
                        <label>24</label>
                        <mixed-citation publication-type="journal">24.	Major Differences. Difference between Global and Local Sequence Alignment. https://www.majordifferences.com/2016/05/difference-between-global-and-local.html. Erişim tarihi: 28.12.2024.</mixed-citation>
                    </ref>
                                    <ref id="ref25">
                        <label>25</label>
                        <mixed-citation publication-type="journal">25.	Likic V., The Needleman–Wunsch Algorithm for Sequence Alignment, Lecture Notes, 7th Melbourne Bioinformatics Course, Molecular Science and Biotechnology Institute, University of Melbourne, 1–46, 2008.</mixed-citation>
                    </ref>
                                    <ref id="ref26">
                        <label>26</label>
                        <mixed-citation publication-type="journal">26.	Needleman S. B., Wunsch C. D., A general method applicable to the search for similarities in the amino acid sequence of two proteins, Journal of Molecular Biology, 48 (3), 443–453, 1970.</mixed-citation>
                    </ref>
                                    <ref id="ref27">
                        <label>27</label>
                        <mixed-citation publication-type="journal">27.	Diamantis S., Charissi A., Comparison of Multiple Sequence Alignment Programs, MSc Bioinformatics Report, National and Kapodistrian University of Athens, 2005.</mixed-citation>
                    </ref>
                                    <ref id="ref28">
                        <label>28</label>
                        <mixed-citation publication-type="journal">28.	Smith T.F., Waterman M.S., Identification of common molecular subsequences, Journal of Molecular Biology, 147 (1), 195–197, 1981.</mixed-citation>
                    </ref>
                                    <ref id="ref29">
                        <label>29</label>
                        <mixed-citation publication-type="journal">29.	Thompson J.D., Higgins D.G., Gibson T.J., CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice, Nucleic Acids Research, 22 (22), 4673–4680, 1994.</mixed-citation>
                    </ref>
                                    <ref id="ref30">
                        <label>30</label>
                        <mixed-citation publication-type="journal">30.	Doğan H., Otu H.H., Objective Functions, Multiple Sequence Alignment Methods, Methods in Molecular Biology, Cilt 1079, Editör: Russell D.J., Springer, 45–58, 2014.</mixed-citation>
                    </ref>
                                    <ref id="ref31">
                        <label>31</label>
                        <mixed-citation publication-type="journal">31.	Sastry K., Goldberg D., Kendall G., Genetic Algorithms, Search Methodologies: Introductory Tutorials in Optimization and Decision Support Techniques, Editör: Burke E.K., Kendall G., Springer, 97–125, 2005.</mixed-citation>
                    </ref>
                                    <ref id="ref32">
                        <label>32</label>
                        <mixed-citation publication-type="journal">32.	Mirjalili S., Evolutionary Algorithms and Neural Networks, Studies in Computational Intelligence, Springer, Berlin, 780, 2019.</mixed-citation>
                    </ref>
                                    <ref id="ref33">
                        <label>33</label>
                        <mixed-citation publication-type="journal">33.	Karaboğa D., Ökdem S., A simple and global optimization algorithm for engineering problems: differential evolution algorithm, Turkish Journal of Electrical Engineering and Computer Sciences, 12 (1), 53–60, 2004.</mixed-citation>
                    </ref>
                                    <ref id="ref34">
                        <label>34</label>
                        <mixed-citation publication-type="journal">34.	Aarts E.H., Van Laarhoven P.J., Simulated annealing: a pedestrian review of the theory and some applications, Pattern Recognition Theory and Applications, Springer, Berlin, 179–192, 1987.
35.	Edgar R.C., Batzoglou S., Multiple sequence alignment, Current Opinion in Structural Biology, 16 (3), 368–373, 2006.</mixed-citation>
                    </ref>
                            </ref-list>
                    </back>
    </article>
