<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Current Bioinformatics</journal-id><journal-title-group><journal-title xml:lang="en">Current Bioinformatics</journal-title><trans-title-group xml:lang="ru"><trans-title>Current Bioinformatics</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1574-8936</issn><issn publication-format="electronic">2212-392X</issn><publisher><publisher-name xml:lang="en">Bentham Science</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">643735</article-id><article-id pub-id-type="doi">10.2174/1574893618666230417104543</article-id><article-categories><subj-group subj-group-type="toc-heading"><subject>Life Sciences</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">SVM-Root: Identification of Root-Associated Proteins in Plants by Employing the Support Vector Machine with Sequence-Derived Features</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Kumar Meher</surname><given-names>Prabina</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name><surname>Hati</surname><given-names>Siddhartha</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name><surname>Sahu</surname><given-names>Tanmaya</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><name><surname>Pradhan</surname><given-names>Upendra</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff4"/></contrib><contrib contrib-type="author"><name><surname>Gupta</surname><given-names>Ajit</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff4"/></contrib><contrib contrib-type="author"><name><surname>Rath</surname><given-names>Surya</given-names></name><email>info@benthamscience.net</email><xref ref-type="aff" rid="aff2"/></contrib></contrib-group><aff id="aff1"><institution>Statistical Genetics, ICAR-Indian Agricultural Statistics Research Institute</institution></aff><aff id="aff2"><institution>Department of Bioinformatics, Odisha University of Agriculture and Technology</institution></aff><aff id="aff3"><institution>Division of Genomic Resources, National Bureau of Plant Genetic Resources</institution></aff><aff id="aff4"><institution>Division of Statistical Genetics, ICAR-Indian Agricultural Statistics Research Institute</institution></aff><pub-date date-type="pub" iso-8601-date="2024-01-01" publication-format="electronic"><day>01</day><month>01</month><year>2024</year></pub-date><volume>19</volume><issue>1</issue><fpage>91</fpage><lpage>102</lpage><history><date date-type="received" iso-8601-date="2025-01-07"><day>07</day><month>01</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2024, Bentham Science Publishers</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="en">Bentham Science Publishers</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/></permissions><self-uri xlink:href="https://journals.eco-vector.com/1574-8936/article/view/643735">https://journals.eco-vector.com/1574-8936/article/view/643735</self-uri><abstract xml:lang="en"><p id="idm46041443744912">Background:Root is a desirable trait for modern plant breeding programs, as the roots play a pivotal role in the growth and development of plants. Therefore, identification of the genes governing the root traits is an essential research component. With regard to the identification of root-associated genes/proteins, the existing wet-lab experiments are resource intensive and the gene expression studies are species-specific. Thus, we proposed a supervised learning-based computational method for the identification of root-associated proteins.</p><p id="idm46041443748912">Method:The problem was formulated as a binary classification, where the root-associated proteins and non-root-associated proteins constituted the two classes. Four different machine learning algorithms such as support vector machine (SVM), extreme gradient boosting, random forest, and adaptive boosting were employed for the classification of proteins of the two classes. Sequence-derived features such as AAC, DPC, CTD, PAAC, and ACF were used as input for the learning algorithms.</p><p id="idm46041443752880">Results:The SVM achieved higher accuracy with the 250 selected features of AAC+DPC+CTD than that of other possible combinations of feature sets and learning algorithms. Specifically, SVM with the selected features achieved overall accuracies of 0.74, 0.73, and 0.73 when evaluated with single 5-fold cross-validation (5F-CV), repeated 5F-CV, and independent test set, respectively.</p><p id="idm46041443757936">Conclusions:A web-enabled prediction tool SVM-Root (https://iasri-sg.icar.gov.in/svmroot/) has been developed for the computational prediction of the root-associated proteins. Being the first of its kind, the proposed model is believed to supplement the existing experimental methods and high throughput GWAS and transcriptome studies.</p></abstract><kwd-group xml:lang="en"><kwd>Root-associated genes</kwd><kwd>machine learning</kwd><kwd>computational biology</kwd><kwd>root system architecture</kwd><kwd>support vector machine</kwd><kwd>artificial intelligence.</kwd></kwd-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Grierson C, Nielsen E, Ketelaarc T, Schiefelbein J. Root hairs. Arabidopsis Book 2014; 2014(12): e0172. doi: 10.1199/tab.0172</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Hayat R, Ali S, Amara U, Khalid R, Ahmed I. Soil beneficial bacteria and their role in plant growth promotion: A review. Ann Microbiol 2010; 60(4): 579-98. doi: 10.1007/s13213-010-0117-1</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Brown LK, George TS, Dupuy LX, White PJ. A conceptual model of root hair ideotypes for future agricultural environments: What combination of traits should be targeted to cope with limited P availability? Ann Bot 2013; 112(2): 317-30. doi: 10.1093/aob/mcs231 PMID: 23172412</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Moisseyev G, Park K, Cui A, et al. RGPDB: Database of root-associated genes and promoters in maize, soybean, and sorghum. Database 2020; 2020: baaa038. doi: 10.1093/database/baaa038</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Coudert Y, Le VAT, Adam H, et al. Identification of CROWN ROOTLESS 1‐regulated genes in rice reveals specific and conserved elements of postembryonic root formation. New Phytol 2015; 206(1): 243-54. doi: 10.1111/nph.13196 PMID: 25442012</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Ober ES, Alahmad S, Cockram J, et al. Wheat root systems as a breeding target for climate resilience. Theor Appl Genet 2021; 134(6): 1645-62. doi: 10.1007/s00122-021-03819-w PMID: 33900415</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Ogura T, Goeschl C, Filiault D, et al. Root system depth in arabidopsis is shaped by EXOCYST70A3 via the dynamic modulation of auxin transport. Cell 2019; 178(2): 400-412.e16. doi: 10.1016/j.cell.2019.06.021 PMID: 31299202</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Li Y, Liu X, Chen R, Tian J, Fan Y, Zhou X. Genome-scale mining of root-preferential genes from maize and characterization of their promoter activity. BMC Plant Biol 2019; 19(1): 584. doi: 10.1186/s12870-019-2198-8 PMID: 31878892</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Lynch JP, Lynch JP. Roots of the second green revolution. Aust J Bot 2007; 55(5): 493-512. doi: 10.1071/BT06118</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Gewin V. Food: An underground revolution. Nature 2010; 466(7306): 552-3. doi: 10.1038/466552a PMID: 20671689</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Coudert Y, Périn C, Courtois B, Khong NG, Gantet P. Genetic control of root development in rice, the model cereal. Trends Plant Sci 2010; 15(4): 219-26. doi: 10.1016/j.tplants.2010.01.008 PMID: 20153971</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Uga Y, Kitomi Y, Ishikawa S, Yano M. Genetic improvement for root growth angle to enhance crop production. Breed Sci 2015; 65(2): 111-9. doi: 10.1270/jsbbs.65.111 PMID: 26069440</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Kalidhasan N, Joshi D, Bhatt T K, Gupta A K. Identification of key genes involved in root development of tomato using expressed sequence tag analysis. Physiol Mol Biol Plants 2015; 21(4): 491-503. doi: 10.1007/s12298-015-0304-4</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Birnbaum K, Shasha DE, Wang JY, et al. A gene expression map of the Arabidopsis root. Science 2003; 302(5652): 1956-60. doi: 10.1126/science.1090022 PMID: 14671301</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Fizames C, Muños S, Cazettes C, et al. The Arabidopsis root transcriptome by serial analysis of gene expression. Gene identification using the genome sequence. Plant Physiol 2004; 134(1): 67-80. doi: 10.1104/pp.103.030536 PMID: 14730065</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Jones M, Smirnoff N. Nuclear dynamics during the simultaneous and sustained tip growth of multiple root hairs arising from a single root epidermal cell. J Exp Bot 2006; 57(15): 4269-75. doi: 10.1093/jxb/erl204 PMID: 17088364</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Markakis MN, De Cnodder T, Lewandowski M, et al. Identification of genes involved in the ACC-mediated control of root cell elongation in Arabidopsis thaliana. BMC Plant Biol 2012; 12(1): 208. doi: 10.1186/1471-2229-12-208 PMID: 23134674</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Toal T W, Ron M, Gibson D, et al. Regulation of root angle and gravitropism. G3 2018; 8(12): 3841-55. doi: 10.1534/g3.118.200540</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Kwasniewski M, Nowakowska U, Szumera J, Chwialkowska K, Szarejko I. iRootHair: A comprehensive root hair genomics database. Plant Physiol 2012; 161(1): 28-35. doi: 10.1104/pp.112.206441 PMID: 23129204</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Qi XH, Xu XW, Lin XJ, Zhang WJ, Chen XH. Identification of differentially expressed genes in cucumber (Cucumis sativus L.) root under waterlogging stress by digital gene expression profile. Genomics 2012; 99(3): 160-8. doi: 10.1016/j.ygeno.2011.12.008 PMID: 22240004</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Halder T, Liu H, Chen Y, Yan G, Siddique KHM. Identification of candidate genes for root traits using genotypephenotype association analysis of near-isogenic lines in hexaploid Wheat (Triticum aestivum L.). Int J Mol Sci 2021; 22(7): 3579. doi: 10.3390/ijms22073579 PMID: 33808237</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Xu F, Chen S, Yang X, et al. Genome-wide association study on root traits under different growing environments in wheat (Triticum aestivum L.). Front Genet 2021; 12: 646712. doi: 10.3389/fgene.2021.646712 PMID: 34178022</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Huang F, Chen Z, Du D, et al. Genome-wide linkage mapping of QTL for root hair length in a Chinese common wheat population. Crop J 2020; 8(6): 1049-56. doi: 10.1016/j.cj.2020.02.007</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Kirschner GK, Rosignoli S, Guo L, et al. Enhanced gravitropism 2 encodes a sterile alpha motifcontaining protein that controls root growth angle in barley and wheat. Proc Natl Acad Sci 2021; 118(35): e2101526118. doi: 10.1073/pnas.2101526118 PMID: 34446550</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Cai YD, Chou KC. Predicting membrane protein type by functional domain composition and pseudo-amino acid composition. J Theor Biol 2006; 238(2): 395-400. doi: 10.1016/j.jtbi.2005.05.035 PMID: 16040052</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Meher PK, Sahu TK, Saini V, Rao AR. Predicting antimicrobial peptides with improved accuracy by incorporating the compositional, physico-chemical and structural features into Chous general PseAAC. Sci Rep 2017; 7(1): 42362. doi: 10.1038/srep42362 PMID: 28205576</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Meher PK, Sahu TK, Mohanty J, et al. nifPred: Proteome-wide identification and categorization of nitrogen-fixation proteins of diaztrophs based on composition-transition-distribution features using support vector machine. Front Microbiol 2018; 9: 1100. doi: 10.3389/fmicb.2018.01100 PMID: 29896173</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Chou KC. Prediction of protein cellular attributes using pseudo-amino acid composition. Proteins 2001; 43(3): 246-55. doi: 10.1002/prot.1035 PMID: 11288174</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Dubchak I, Muchnik I, Holbrook SR, Kim SH. Prediction of protein folding class using global description of amino acid sequence. Proc Natl Acad Sci 1995; 92(19): 8700-4. doi: 10.1073/pnas.92.19.8700 PMID: 7568000</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Govindan G, Nair AS. Composition, transition and distribution CTD - A dynamic feature for predictions based on hierarchical structure of cellular sorting. Proceedings - 2011 Annual IEEE India Conference: Engineering Sustainable Solutions, INDICON-2011. doi: 10.1109/INDCON.2011.6139332</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Liu W, Chou KC. Prediction of protein structural classes by modified mahalanobis discriminant algorithm. J Protein Chem 1998; 17(3): 209-17. doi: 10.1023/A:1022576400291 PMID: 9588944</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Zhang CT, Lin ZS, Zhang Z, Yan M. Prediction of the helix/strand content of globular proteins based on their primary sequences. Protein Eng Des Sel 1998; 11(11): 971-9. doi: 10.1093/protein/11.11.971 PMID: 9876917</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Ding Y, Cai Y, Zhang G, Xu W. The influence of dipeptide composition on protein thermostability. FEBS Lett 2004; 569(1-3): 284-8. doi: 10.1016/j.febslet.2004.06.009 PMID: 15225649</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Wang YC, Wang XB, Yang ZX, Deng NY. Prediction of enzyme subfamily class via pseudo amino acid composition by incorporating the conjoint triad feature. Protein Pept Lett 2010; 17(11): 1441-9. doi: 10.2174/0929866511009011441 PMID: 20666729</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Kawashima S, Kanehisa M. AAindex: Amino acid index database. Nucleic Acids Res 2000; 28(1): 374-4. doi: 10.1093/nar/28.1.374 PMID: 10592278</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Xiao N, Cao DS, Zhu MF, Xu QS. protr/ProtrWeb: R package and web server for generating various numerical representation schemes of protein sequences. Bioinformatics 2015; 31(11): 1857-9. doi: 10.1093/bioinformatics/btv042 PMID: 25619996</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Li H. Using the BioSeqClass Package. Homo. 2010; pp. 1-18. Available from: https://www.bioconductor.org/packages//2.7/bioc/vignettes/BioSeqClass/inst/doc/BioSeqClass.pdf</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Guyon I, Weston J, Barnhill S, Vapnik V. Gene selection for cancer classification using support vector machines. Mach Learn 2002; 46(1/3): 389-422. doi: 10.1023/A:1012487302797</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Harikrishna S, Farquad MAH, Shabana . Credit scoring using support vector machine: A comparative analysis. Adv Mat Res 2012; 433(440): 6527-6533,-. doi: 10.4028/www.scientific.net/AMR.433-440.6527</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>Lin X, Yang F, Zhou L, et al. A support vector machine-recursive feature elimination feature selection method based on artificial contrast variables and mutual information. J Chromatogr B Analyt Technol Biomed Life Sci 2012; 910: 149-55. doi: 10.1016/j.jchromb.2012.05.020 PMID: 22682888</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>Huang ML, Hung YH, Lee WM, Li RK, Jiang BR. SVM-RFE based feature selection and Taguchi parameters optimization for multiclass SVM classifier. ScientificWorldJournal 2014; 2014: 1-10. doi: 10.1155/2014/795624 PMID: 25295306</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>Meher PK, Begam S, Sahu TK, et al. ASRmiRNA: Abiotic stress-responsive mirna prediction in plants by using machine learning algorithms with pseudo K-Tuple Nucleotide compositional features. Int J Mol Sci 2022; 23(3): 1612. doi: 10.3390/ijms23031612 PMID: 35163534</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>Das P, Roychowdhury A, Das S, Roychoudhury S, Tripathy S. sigFeature: Novel significant feature selection method for classification of gene expression data using support vector machine and t statistic. Front Genet 2020; 11: 247. doi: 10.3389/fgene.2020.00247 PMID: 32346383</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>Cortes C, Vapnik V. Support-vector networks. Mach Learn 1995; 20(3): 273-97. doi: 10.1007/BF00994018</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>Breiman L. Random forests. Mach Learn 2001; 45(1): 5-32. doi: 10.1023/A:1010933404324</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>Freund Y, Schapire RE. Experiments with a new boosting algorithm. In Proceedings of the 13th International Conference on Machine Learning. San Fransisco, USA. 1996; pp. 148-56.</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>Chen T, Guestrin C. XGBoost: A scalable tree boosting system. In Proceedings of the ACM SIGKDD International Conference on Knowledge Discovery and Data Mining. Anchorage, USA. 2019; pp. 13-7. doi: 10.1145/2939672.2939785</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>Dimitriadou AE, Hornik K, Leisch F, Meyer D, Weingessel A, Friedrichleischcituwienacat MFL. The E1071 Package. 2014. Available from: https://cran.r-project.org/web/packages/e1071/index.html</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>Liaw A, Wiener M. Classification and regression by random forest. R News 2002; 2: 18-22. Available from: https://cogns.northwestern.edu/cbmg/LiawAndWiener2002.pdf</mixed-citation></ref><ref id="B50"><label>50.</label><mixed-citation>Alfaro E, Gámez M, García N. adabag: An R package for classification with boosting and bagging. J Stat Softw 2013; 54(2): 1-35. doi: 10.18637/jss.v054.i02</mixed-citation></ref><ref id="B51"><label>51.</label><mixed-citation>xgboost: Extreme Gradient Boosting version 1.6.0.1 from CRAN. Available from: https://rdrr.io/cran/xgboost/ (accessed 2022-04-21).</mixed-citation></ref><ref id="B52"><label>52.</label><mixed-citation>Fawcett T. An introduction to ROC analysis. Pattern Recognit Lett 2006; 27(8): 861-74. doi: 10.1016/j.patrec.2005.10.010</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>Davis J, Goadrich M. The relationship between precision-recall and ROC curves. In. ACM International Conference Proceeding Series. New York, USA: ACM 2006; pp. 233-40. doi: 10.1145/1143844.1143874</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>Manschadi AM, Kaul HP, Vollmann J, Eitzinger J, Wenzel W. Developing phosphorus-efficient crop varieties-An interdisciplinary research framework. Field Crops Res 2014; 162: 87-98. doi: 10.1016/j.fcr.2013.12.016</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>Comas LH, Becker SR, Cruz VMV, Byrne PF, Dierig DA. Root traits contributing to plant productivity under drought. Front Plant Sci 2013; 4: 442. doi: 10.3389/fpls.2013.00442 PMID: 24204374</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>Fenta B, Beebe S, Kunert K, et al. Field phenotyping of soybean roots for drought stress tolerance. Agronomy 2014; 4(3): 418-35. doi: 10.3390/agronomy4030418</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>Wade LJ, Bartolome V, Mauleon R, et al. Environmental response and genomic regions correlated with rice root growth and yield under drought in the oryzasnp panel across multiple study systems. PLoS One 2015; 10(4): e0124127. doi: 10.1371/journal.pone.0124127 PMID: 25909711</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>Rosas-Quijano R, Ontiveros-Cisneros A, Montes-García N, et al. A General Overview of Sweet Sorghum Genomics. London, UK: IntechOpen 2021. doi: 10.5772/intechopen.98539</mixed-citation></ref><ref id="B59"><label>59.</label><mixed-citation>Brendel V, Kurtz S, Walbot V. Comparative genomics of Arabidopsis and maize: Prospects and limitations. Genome Biol 2002; 3(3): reviews1005.1. doi: 10.1186/gb-2002-3-3-reviews1005 PMID: 11897028</mixed-citation></ref><ref id="B60"><label>60.</label><mixed-citation>Paterson AH. Genomics of sorghum. Int J Plant Genomics 2008; 2008: 1-6. doi: 10.1155/2008/362451 PMID: 18483564</mixed-citation></ref><ref id="B61"><label>61.</label><mixed-citation>Traore SM, He G, Traore SM, He G. Soybean as a Model Crop to Study Plant Oil Genes: Mutations in FAD2 Gene Family. London. UK: IntechOpen 2021. doi: 10.5772/intechopen.99752</mixed-citation></ref><ref id="B62"><label>62.</label><mixed-citation>Ferguson BJ, Gresshoff PM. Soybean as a model legume. Grain Legumes 2009; 53: 7.</mixed-citation></ref></ref-list></back></article>
