{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T22:30:47Z","timestamp":1723069847975},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"S5","license":[{"start":{"date-parts":[[2006,12,1]],"date-time":"2006-12-01T00:00:00Z","timestamp":1164931200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/2.0"},{"start":{"date-parts":[[2006,12,18]],"date-time":"2006-12-18T00:00:00Z","timestamp":1166400000000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2006,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Antigenic diversity in dengue virus strains has been studied, but large-scale and detailed systematic analyses have not been reported. In this study, we report a bioinformatics method for analyzing viral antigenic diversity in the context of T-cell mediated immune responses. We applied this method to study the relationship between short-peptide antigenic diversity and protein sequence diversity of dengue virus. We also studied the effects of sequence determinants on viral antigenic diversity. Short peptides, principally 9-mers were studied because they represent the predominant length of binding cores of T-cell epitopes, which are important for formulation of vaccines.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Our analysis showed that the number of unique protein sequences required to represent complete antigenic diversity of short peptides in dengue virus is significantly smaller than that required to represent complete protein sequence diversity. Short-peptide antigenic diversity shows an asymptotic relationship to the number of unique protein sequences, indicating that for large sequence sets (~200) the addition of new protein sequences has marginal effect to increasing antigenic diversity. A near-linear relationship was observed between the extent of antigenic diversity and the length of protein sequences, suggesting that, for the practical purpose of vaccine development, antigenic diversity of short peptides from dengue virus can be represented by short regions of sequences (~<100 aa) within viral antigens that are specific targets of immune responses (such as T-cell epitopes specific to particular human leukocyte antigen alleles).<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n This study provides evidence that there are limited numbers of antigenic combinations in protein sequence variants of a viral species and that short regions of the viral protein are sufficient to capture antigenic diversity of T-cell epitopes. The approach described herein has direct application to the analysis of other viruses, in particular those that show high diversity and\/or rapid evolution, such as influenza A virus and human immunodeficiency virus (HIV).<\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/1471-2105-7-s5-s4","type":"journal-article","created":{"date-parts":[[2006,12,19]],"date-time":"2006-12-19T07:17:26Z","timestamp":1166512646000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Large-scale analysis of antigenic diversity of T-cell epitopes in dengue virus"],"prefix":"10.1186","volume":"7","author":[{"given":"Asif M","family":"Khan","sequence":"first","affiliation":[]},{"given":"AT","family":"Heiny","sequence":"additional","affiliation":[]},{"given":"Kenneth X","family":"Lee","sequence":"additional","affiliation":[]},{"given":"KN","family":"Srinivasan","sequence":"additional","affiliation":[]},{"given":"Tin Wee","family":"Tan","sequence":"additional","affiliation":[]},{"given":"J Thomas","family":"August","sequence":"additional","affiliation":[]},{"given":"Vladimir","family":"Brusic","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2006,12,18]]},"reference":[{"issue":"2","key":"1354_CR1","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1016\/0042-6822(92)90560-C","volume":"188","author":"J Fu","year":"1992","unstructured":"Fu J, Tan BH, Yap EH, Chan YC, Tan YH: Full-length cDNA sequence of dengue type 1 virus (Singapore strain S275\/90). Virology 1992, 188(2):953\u2013958. 10.1016\/0042-6822(92)90560-C","journal-title":"Virology"},{"issue":"7","key":"1354_CR2","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1038\/nm887","volume":"9","author":"J Mongkolsapaya","year":"2003","unstructured":"Mongkolsapaya J, Dejnirattisai W, Xu XN, Vasanawathana S, Tangthawornchaikul N, Chairunsri A, Sawasdivorn S, Duangchinda T, Dong T, Rowland-Jones S, et al.: Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever. Nat Med 2003, 9(7):921\u2013927. 10.1038\/nm887","journal-title":"Nat Med"},{"issue":"2","key":"1354_CR3","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/S0966-842X(99)01669-8","volume":"8","author":"EC Holmes","year":"2000","unstructured":"Holmes EC, Burch SS: The causes and consequences of genetic variation in dengue virus. Trends Microbiol 2000, 8(2):74\u201377. 10.1016\/S0966-842X(99)01669-8","journal-title":"Trends Microbiol"},{"issue":"24","key":"1354_CR4","doi-asserted-by":"publisher","first-page":"15123","DOI":"10.1128\/JVI.79.24.15123-15130.2005","volume":"79","author":"C Zhang","year":"2005","unstructured":"Zhang C, Mammen MP Jr, Chinnawirotpisan P, Klungthong C, Rodpradit P, Monkongdee P, Nimmannitya S, Kalayanarooj S, Holmes EC: Clade replacements in dengue virus serotypes 1 and 3 are associated with changing serotype prevalence. J Virol 2005, 79(24):15123\u201315130. 10.1128\/JVI.79.24.15123-15130.2005","journal-title":"J Virol"},{"key":"1354_CR5","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/1743-422X-2-72","volume":"2","author":"DY Chao","year":"2005","unstructured":"Chao DY, King CC, Wang WK, Chen WJ, Wu HL, Chang GJ: Strategically examining the full-genome of dengue virus type 3 in clinical isolates reveals its mutation spectra. Virol J 2005, 2: 72. 10.1186\/1743-422X-2-72","journal-title":"Virol J"},{"key":"1354_CR6","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/1743-422X-2-40","volume":"2","author":"CH Schein","year":"2005","unstructured":"Schein CH, Zhou B, Braun W: Stereophysicochemical variability plots highlight conserved antigenic areas in Flaviviruses. Virol J 2005, 2: 40. 10.1186\/1743-422X-2-40","journal-title":"Virol J"},{"issue":"4","key":"1354_CR7","first-page":"646","volume":"21","author":"PR Young","year":"1990","unstructured":"Young PR: Antigenic analysis of dengue virus using monoclonal antibodies. Southeast Asian J Trop Med Public Health 1990, 21(4):646\u2013651.","journal-title":"Southeast Asian J Trop Med Public Health"},{"issue":"1","key":"1354_CR8","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1111\/j.1348-0421.1993.tb03177.x","volume":"37","author":"N Maneekarn","year":"1993","unstructured":"Maneekarn N, Morita K, Tanaka M, Igarashi A, Usawattanakul W, Sirisanthana V, Innis BL, Sittisombut N, Nisalak A, Nimmanitya S: Applications of polymerase chain reaction for identification of dengue viruses isolated from patient sera. Microbiol Immunol 1993, 37(1):41\u201347.","journal-title":"Microbiol Immunol"},{"issue":"1","key":"1354_CR9","doi-asserted-by":"crossref","first-page":"100","DOI":"10.4269\/ajtmh.1997.57.100","volume":"57","author":"N Sittisombut","year":"1997","unstructured":"Sittisombut N, Sistayanarain A, Cardosa MJ, Salminen M, Damrongdachakul S, Kalayanarooj S, Rojanasuphot S, Supawadee J, Maneekarn N: Possible occurrence of a genetic bottleneck in dengue serotype 2 viruses between the 1980 and 1987 epidemic seasons in Bangkok, Thailand. Am J Trop Med Hyg 1997, 57(1):100\u2013108.","journal-title":"Am J Trop Med Hyg"},{"issue":"6","key":"1354_CR10","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1590\/S0036-46651998000600002","volume":"40","author":"SS Baba","year":"1998","unstructured":"Baba SS, Fagbami AH, Olaleye OD: Antigenic relatedness of selected flaviviruses: study with homologous and heterologous immune mouse ascitic fluids. Rev Inst Med Trop Sao Paulo 1998, 40(6):343\u2013349.","journal-title":"Rev Inst Med Trop Sao Paulo"},{"issue":"2","key":"1354_CR11","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1128\/CDLI.12.2.361-362.2005","volume":"12","author":"L Bernardo","year":"2005","unstructured":"Bernardo L, Yndart A, Vazquez S, Morier L, Guzman MG: Antibody responses to Asian and American genotypes of dengue 2 virus in immunized mice. Clin Diagn Lab Immunol 2005, 12(2):361\u2013362. 10.1128\/CDLI.12.2.361-362.2005","journal-title":"Clin Diagn Lab Immunol"},{"issue":"5","key":"1354_CR12","doi-asserted-by":"crossref","first-page":"3108","DOI":"10.1128\/jvi.70.5.3108-3117.1996","volume":"70","author":"L Zeng","year":"1996","unstructured":"Zeng L, Kurane I, Okamoto Y, Ennis FA, Brinton MA: Identification of amino acids involved in recognition by dengue virus NS3-specific, HLA-DR15-restricted cytotoxic CD4+ T-cell clones. J Virol 1996, 70(5):3108\u20133117.","journal-title":"J Virol"},{"issue":"2","key":"1354_CR13","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1006\/viro.1997.8925","volume":"240","author":"I Kurane","year":"1998","unstructured":"Kurane I, Zeng L, Brinton MA, Ennis FA: Definition of an epitope on NS3 recognized by human CD4+ cytotoxic T lymphocyte clones cross-reactive for dengue virus types 2, 3, and 4. Virology 1998, 240(2):169\u2013174. 10.1006\/viro.1997.8925","journal-title":"Virology"},{"issue":"11","key":"1354_CR14","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1086\/324320","volume":"184","author":"H Loke","year":"2001","unstructured":"Loke H, Bethell DB, Phuong CX, Dung M, Schneider J, White NJ, Day NP, Farrar J, Hill AV: Strong HLA class I \u2013 restricted T cell responses in dengue hemorrhagic fever: a double-edged sword? J Infect Dis 2001, 184(11):1369\u20131373. 10.1086\/324320","journal-title":"J Infect Dis"},{"issue":"9","key":"1354_CR15","doi-asserted-by":"publisher","first-page":"5665","DOI":"10.1128\/JVI.79.9.5665-5675.2005","volume":"79","author":"CP Simmons","year":"2005","unstructured":"Simmons CP, Dong T, Chau NV, Dung NT, Chau TN, Thao le TT, Dung NT, Hien TT, Rowland-Jones S, Farrar J: Early T-cell responses to dengue virus epitopes in Vietnamese adults with secondary dengue virus infections. J Virol 2005, 79(9):5665\u20135675. 10.1128\/JVI.79.9.5665-5675.2005","journal-title":"J Virol"},{"issue":"6","key":"1354_CR16","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/0923-2516(90)90039-L","volume":"141","author":"J Morvan","year":"1990","unstructured":"Morvan J, Besselaar T, Fontenille D, Coulanges P: Antigenic variations in West Nile virus strains isolated in Madagascar since 1978. Res Virol 1990, 141(6):667\u2013676. 10.1016\/0923-2516(90)90039-L","journal-title":"Res Virol"},{"issue":"5682","key":"1354_CR17","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1126\/science.1097211","volume":"305","author":"DJ Smith","year":"2004","unstructured":"Smith DJ, Lapedes AS, de Jong JC, Bestebroer TM, Rimmelzwaan GF, Osterhaus AD, Fouchier RA: Mapping the antigenic and genetic evolution of influenza virus. Science 2004, 305(5682):371\u2013376. 10.1126\/science.1097211","journal-title":"Science"},{"key":"1354_CR18","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/S0065-3527(03)59009-1","volume":"59","author":"R Rico-Hesse","year":"2003","unstructured":"Rico-Hesse R: Microevolution and virulence of dengue viruses. Adv Virus Res 2003, 59: 315\u2013341.","journal-title":"Adv Virus Res"},{"issue":"Database","key":"1354_CR19","doi-asserted-by":"publisher","first-page":"D39","DOI":"10.1093\/nar\/gki062","volume":"33","author":"DL Wheeler","year":"2005","unstructured":"Wheeler DL, Barrett T, Benson DA, Bryant SH, Canese K, Church DM, DiCuccio M, Edgar R, Federhen S, Helmberg W, et al.: Database resources of the National Center for Biotechnology Information. Nucleic Acids Res 2005, 33(Database):D39\u201345. 10.1093\/nar\/gki062","journal-title":"Nucleic Acids Res"},{"issue":"7\u20138","key":"1354_CR20","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1016\/S0264-410X(01)00441-8","volume":"20","author":"J Ho","year":"2002","unstructured":"Ho J, MacDonald KS, Barber BH: Construction of recombinant targeting immunogens incorporating an HIV-1 neutralizing epitope into sites of differing conformational constraint. Vaccine 2002, 20(7\u20138):1169\u20131180. 10.1016\/S0264-410X(01)00441-8","journal-title":"Vaccine"},{"key":"1354_CR21","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1471-2172-7-7","volume":"7","author":"J Huang","year":"2006","unstructured":"Huang J, Honda W: CED: a conformational epitope database. BMC Immunol 2006, 7: 7. 10.1186\/1471-2172-7-7","journal-title":"BMC Immunol"},{"issue":"2","key":"1354_CR22","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/0042-6822(90)90102-W","volume":"174","author":"R Rico-Hesse","year":"1990","unstructured":"Rico-Hesse R: Molecular evolution and distribution of dengue viruses type 1 and 2 in nature. Virology 1990, 174(2):479\u2013493. 10.1016\/0042-6822(90)90102-W","journal-title":"Virology"},{"issue":"1","key":"1354_CR23","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1006\/viro.2002.1447","volume":"298","author":"SS Twiddy","year":"2002","unstructured":"Twiddy SS, Farrar JJ, Vinh Chau N, Wills B, Gould EA, Gritsun T, Lloyd G, Holmes EC: Phylogenetic relationships and differential selection pressures among genotypes of dengue-2 virus. Virology 2002, 298(1):63\u201372. 10.1006\/viro.2002.1447","journal-title":"Virology"},{"issue":"1","key":"1354_CR24","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/S1567-1348(03)00004-2","volume":"3","author":"EC Holmes","year":"2003","unstructured":"Holmes EC, Twiddy SS: The origin, emergence and evolutionary genetics of dengue virus. Infect Genet Evol 2003, 3(1):19\u201328. 10.1016\/S1567-1348(03)00004-2","journal-title":"Infect Genet Evol"},{"issue":"1","key":"1354_CR25","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1093\/molbev\/msg010","volume":"20","author":"SS Twiddy","year":"2003","unstructured":"Twiddy SS, Holmes EC, Rambaut A: Inferring the rate and time-scale of dengue virus evolution. Mol Biol Evol 2003, 20(1):122\u2013129. 10.1093\/molbev\/msg010","journal-title":"Mol Biol Evol"},{"issue":"2","key":"1354_CR26","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/0042-6822(91)90540-R","volume":"185","author":"F Preugschat","year":"1991","unstructured":"Preugschat F, Strauss JH: Processing of nonstructural proteins NS4A and NS4B of dengue 2 virus in vitro and in vivo. Virology 1991, 185(2):689\u2013697. 10.1016\/0042-6822(91)90540-R","journal-title":"Virology"},{"issue":"1","key":"1354_CR27","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/nrmicro1067","volume":"3","author":"S Mukhopadhyay","year":"2005","unstructured":"Mukhopadhyay S, Kuhn RJ, Rossmann MG: A structural perspective of the flavivirus life cycle. Nat Rev Microbiol 2005, 3(1):13\u201322. 10.1038\/nrmicro1067","journal-title":"Nat Rev Microbiol"},{"issue":"9341","key":"1354_CR28","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1016\/S0140-6736(02)11276-1","volume":"360","author":"SB Halstead","year":"2002","unstructured":"Halstead SB, Deen J: The future of dengue vaccines. Lancet 2002, 360(9341):1243\u20131245. 10.1016\/S0140-6736(02)11276-1","journal-title":"Lancet"},{"issue":"6","key":"1354_CR29","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1517\/14622416.5.6.597","volume":"5","author":"V Brusic","year":"2004","unstructured":"Brusic V, August JT: The changing field of vaccine development in the genomics era. Pharmacogenomics 2004, 5(6):597\u2013600. 10.1517\/14622416.5.6.597","journal-title":"Pharmacogenomics"},{"issue":"4","key":"1354_CR30","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1517\/14622416.5.4.417","volume":"5","author":"IG Ovsyannikova","year":"2004","unstructured":"Ovsyannikova IG, Jacobson RM, Poland GA: Variation in vaccine response in normal populations. Pharmacogenomics 2004, 5(4):417\u2013427. 10.1517\/14622416.5.4.417","journal-title":"Pharmacogenomics"},{"issue":"Suppl 1","key":"1354_CR31","doi-asserted-by":"publisher","first-page":"I297","DOI":"10.1093\/bioinformatics\/bth943","volume":"20","author":"KN Srinivasan","year":"2004","unstructured":"Srinivasan KN, Zhang GL, Khan AM, August JT, Brusic V: Prediction of class I T-cell epitopes: evidence of presence of immunological hot spots inside antigens. Bioinformatics 2004, 20(Suppl 1):I297-I302. 10.1093\/bioinformatics\/bth943","journal-title":"Bioinformatics"},{"issue":"1","key":"1354_CR32","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/0952-7915(95)80033-6","volume":"7","author":"HG Rammensee","year":"1995","unstructured":"Rammensee HG: Chemistry of peptides associated with MHC class I and class II molecules. Curr Opin Immunol 1995, 7(1):85\u201396. 10.1016\/0952-7915(95)80033-6","journal-title":"Curr Opin Immunol"},{"issue":"2\u20133","key":"1354_CR33","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/S0928-0197(98)00039-7","volume":"10","author":"MA Brinton","year":"1998","unstructured":"Brinton MA, Kurane I, Mathew A, Zeng L, Shi PY, Rothman A, Ennis FA: Immune mediated and inherited defences against flaviviruses. Clin Diagn Virol 1998, 10(2\u20133):129\u2013139. 10.1016\/S0928-0197(98)00039-7","journal-title":"Clin Diagn Virol"},{"key":"1354_CR34","unstructured":"NCBI Entrez protein database[http:\/\/www.ncbi.nlm.nih.gov\/entrez]"},{"issue":"2","key":"1354_CR35","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/0042-6822(90)90037-R","volume":"176","author":"K Osatomi","year":"1990","unstructured":"Osatomi K, Sumiyoshi H: Complete nucleotide sequence of dengue type 3 virus genome RNA. Virology 1990, 176(2):643\u2013647. 10.1016\/0042-6822(90)90037-R","journal-title":"Virology"},{"issue":"Web Server","key":"1354_CR36","doi-asserted-by":"publisher","first-page":"W20","DOI":"10.1093\/nar\/gkh435","volume":"32","author":"S McGinnis","year":"2004","unstructured":"McGinnis S, Madden TL: BLAST: at the core of a powerful and diverse set of sequence analysis tools. Nucleic Acids Res 2004, 32(Web Server):W20\u201325. 10.1093\/nar\/gkh435","journal-title":"Nucleic Acids Res"},{"issue":"24","key":"1354_CR37","doi-asserted-by":"publisher","first-page":"4876","DOI":"10.1093\/nar\/25.24.4876","volume":"25","author":"JD Thompson","year":"1997","unstructured":"Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG: The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 1997, 25(24):4876\u20134882. 10.1093\/nar\/25.24.4876","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"1354_CR38","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S0041-0101(01)00182-9","volume":"40","author":"KN Srinivasan","year":"2002","unstructured":"Srinivasan KN, Gopalakrishnakone P, Tan PT, Chew KC, Cheng B, Kini RM, Koh JL, Seah SH, Brusic V: SCORPION, a molecular database of scorpion toxins. Toxicon 2002, 40(1):23\u201331. 10.1016\/S0041-0101(01)00182-9","journal-title":"Toxicon"},{"issue":"22","key":"1354_CR39","doi-asserted-by":"publisher","first-page":"4673","DOI":"10.1093\/nar\/22.22.4673","volume":"22","author":"JD Thompson","year":"1994","unstructured":"Thompson JD, Higgins DG, Gibson TJ: CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 1994, 22(22):4673\u20134680. 10.1093\/nar\/22.22.4673","journal-title":"Nucleic Acids Res"},{"key":"1354_CR40","doi-asserted-by":"publisher","first-page":"6893","DOI":"10.1016\/j.vaccine.2006.06.009","volume":"24","author":"F Li","year":"2006","unstructured":"Li F, Malhotra U, Gilbert PB, Hawkins NR, Duerr AC, McElrath JM, Corey L, Self SG: Peptide selection for human immunodeficiency virus type 1 CTL-based vaccine evaluation. Vaccine 2006, 24: 6893\u20136904. 10.1016\/j.vaccine.2006.06.009","journal-title":"Vaccine"},{"key":"1354_CR41","first-page":"313","volume":"6","author":"V Brusic","year":"1999","unstructured":"Brusic V, Zeleznikow J: Computational binding assays of antigenic peptides. Lett Pept Sci 1999, 6: 313\u2013324.","journal-title":"Lett Pept Sci"},{"key":"1354_CR42","unstructured":"HLA Informatics Group[http:\/\/www.anthonynolan.org.uk\/HIG]"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-7-S5-S4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/1471-2105-7-S5-S4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-7-S5-S4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T02:32:40Z","timestamp":1630463560000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-7-S5-S4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,12]]},"references-count":42,"journal-issue":{"issue":"S5","published-print":{"date-parts":[[2006,12]]}},"alternative-id":["1354"],"URL":"https:\/\/doi.org\/10.1186\/1471-2105-7-s5-s4","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,12]]},"assertion":[{"value":"18 December 2006","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"S4"}}