{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T02:39:43Z","timestamp":1769913583543,"version":"3.49.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Tuberculosis is currently the second highest cause of death from infectious diseases worldwide. The emergence of multi and extensive drug resistance is threatening to make tuberculosis incurable. There is growing evidence that the genetic diversity of <jats:italic>Mycobacterium tuberculosis<\/jats:italic> may have important clinical consequences. Therefore, combining genetic, clinical and socio-demographic data is critical to understand the epidemiology of this infectious disease, and how virulence and other phenotypic traits evolve over time. This requires dedicated bioinformatics platforms, capable of integrating and enabling analyses of this heterogeneous data.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We developed inTB, a web-based system for integrated warehousing and analysis of clinical, socio-demographic and molecular data for <jats:italic>Mycobacterium sp.<\/jats:italic> isolates. As a database it can organize and display data from any of the standard genotyping methods (SNP, MIRU-VNTR, RFLP and spoligotype), as well as an extensive array of clinical and socio-demographic variables that are used in multiple countries to characterize the disease. Through the inTB interface it is possible to insert and download data, browse the database and search specific parameters. New isolates are automatically classified into strains according to an internal reference, and data uploaded or typed in is checked for internal consistency. As an analysis framework, the system provides simple, point and click analysis tools that allow multiple types of data plotting, as well as simple ways to download data for external analysis. Individual trees for each genotyping method are available, as well as a super tree combining all of them. The integrative nature of inTB grants the user the ability to generate trees for filtered subsets of data crossing molecular and clinical\/socio-demografic information. inTB is built on open source software, can be easily installed locally and easily adapted to other diseases. Its design allows for use by research laboratories, hospitals or public health authorities. The full source code as well as ready to use packages is available at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.evocell.org\/inTB\" ext-link-type=\"uri\">http:\/\/www.evocell.org\/inTB<\/jats:ext-link>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>To the best of our knowledge, this is the only system capable of integrating different types of molecular data with clinical and socio-demographic data, empowering researchers and clinicians with easy to use analysis tools that were not possible before.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2105-14-264","type":"journal-article","created":{"date-parts":[[2013,8,30]],"date-time":"2013-08-30T18:14:19Z","timestamp":1377886459000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["inTB - a data integration platform for molecular and clinical epidemiological analysis of tuberculosis"],"prefix":"10.1186","volume":"14","author":[{"given":"Patr\u00edcia","family":"Soares","sequence":"first","affiliation":[]},{"given":"Renato J","family":"Alves","sequence":"additional","affiliation":[]},{"given":"Ana B","family":"Abecasis","sequence":"additional","affiliation":[]},{"given":"Carlos","family":"Penha-Gon\u00e7alves","sequence":"additional","affiliation":[]},{"given":"M Gabriela M","family":"Gomes","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 B","family":"Pereira-Leal","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2013,8,30]]},"reference":[{"key":"6040_CR1","volume-title":"Global tuberculosis control: WHO report 2011","author":"World Health Organization","year":"2011","unstructured":"World Health Organization: Global tuberculosis control: WHO report 2011. 2011, Geneva, Switzerland: World Health Organization, 2011"},{"key":"6040_CR2","doi-asserted-by":"publisher","first-page":"e7815","DOI":"10.1371\/journal.pone.0007815","volume":"4","author":"I Comas","year":"2009","unstructured":"Comas I, Homolka S, Niemann S, Gagneux S: Genotyping of genetically monomorphic bacteria: DNA sequencing in Mycobacterium tuberculosis highlights the limitations of current methodologies. PLoS ONE. 2009, 4: e7815-10.1371\/journal.pone.0007815.","journal-title":"PLoS ONE"},{"key":"6040_CR3","doi-asserted-by":"publisher","first-page":"e311","DOI":"10.1371\/journal.pbio.0060311","volume":"6","author":"R Hershberg","year":"2008","unstructured":"Hershberg R, Lipatov M, Small PM, Sheffer H, Niemann S, Homolka S, Roach JC, Kremer K, Petrov DA, Feldman MW, Gagneux S: High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography. PLoS Biol. 2008, 6: e311-10.1371\/journal.pbio.0060311.","journal-title":"PLoS Biol"},{"key":"6040_CR4","doi-asserted-by":"publisher","first-page":"e43","DOI":"10.1016\/j.ddmec.2010.09.004","volume":"7","author":"M Coscolla","year":"2010","unstructured":"Coscolla M, Gagneux S: Does M. tuberculosis genomic diversity explain disease diversity?. Drug Discovery Today: Disease Mechanisms. 2010, 7: e43-e59.","journal-title":"Drug Discovery Today: Disease Mechanisms"},{"key":"6040_CR5","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1136\/ewjm.172.4.256","volume":"172","author":"M Kato-Maeda","year":"2000","unstructured":"Kato-Maeda M, Small PM: How molecular epidemiology has changed what we know about tuberculosis. West J Med. 2000, 172: 256-259. 10.1136\/ewjm.172.4.256.","journal-title":"West J Med"},{"key":"6040_CR6","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1128\/JCM.02180-07","volume":"46","author":"G Thwaites","year":"2008","unstructured":"Thwaites G, Caws M, Chau TTH, D\u2019Sa A, Lan NTN, Huyen MNT, Gagneux S, Anh PTH, Tho DQ, Torok E, Nhu NTQ, Duyen NTH, Duy PM, Richenberg J, Simmons C, Hien TT, Farrar J: Relationship between Mycobacterium tuberculosis genotype and the clinical phenotype of pulmonary and meningeal tuberculosis. J Clin Microbiol. 2008, 46: 1363-1368. 10.1128\/JCM.02180-07.","journal-title":"J Clin Microbiol"},{"key":"6040_CR7","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/j.trstmh.2008.03.025","volume":"102","author":"MP Nicol","year":"2008","unstructured":"Nicol MP, Wilkinson RJ: The clinical consequences of strain diversity in Mycobacterium tuberculosis. Trans R Soc Trop Med Hyg. 2008, 102: 955-965. 10.1016\/j.trstmh.2008.03.025.","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"6040_CR8","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1046\/j.1365-2958.2000.01905.x","volume":"36","author":"P Supply","year":"2000","unstructured":"Supply P, Mazars E, Lesjean S, Vincent V, Gicquel B, Locht C: Variable human minisatellite-like regions in the Mycobacterium tuberculosis genome. Mol Microbiol. 2000, 36: 762-771.","journal-title":"Mol Microbiol"},{"key":"6040_CR9","doi-asserted-by":"publisher","first-page":"3563","DOI":"10.1128\/JCM.39.10.3563-3571.2001","volume":"39","author":"P Supply","year":"2001","unstructured":"Supply P, Lesjean S, Savine E, Kremer K, van Soolingen D, Locht C: Automated high-throughput genotyping for study of global epidemiology of Mycobacterium tuberculosis based on mycobacterial interspersed repetitive units. J Clin Microbiol. 2001, 39: 3563-3571. 10.1128\/JCM.39.10.3563-3571.2001.","journal-title":"J Clin Microbiol"},{"key":"6040_CR10","doi-asserted-by":"publisher","first-page":"4498","DOI":"10.1128\/JCM.01392-06","volume":"44","author":"P Supply","year":"2006","unstructured":"Supply P, Allix C, Lesjean S, Cardoso-Oelemann M, R\u00fcsch-Gerdes S, Willery E, Savine E, de Haas P, van Deutekom H, Roring S, Bifani P, Kurepina N, Kreiswirth B, Sola C, Rastogi N, Vatin V, Gutierrez MC, Fauville M, Niemann S, Skuce R, Kremer K, Locht C, van Soolingen D: Proposal for standardization of optimized mycobacterial interspersed repetitive unit-variable-number tandem repeat typing of Mycobacterium tuberculosis. J Clin Microbiol. 2006, 44: 4498-4510. 10.1128\/JCM.01392-06.","journal-title":"J Clin Microbiol"},{"key":"6040_CR11","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1016\/j.meegid.2009.09.006","volume":"9","author":"J Millet","year":"2009","unstructured":"Millet J, Baboolal S, Akpaka PE, Ramoutar D, Rastogi N: Phylogeographical and molecular characterization of an emerging Mycobacterium tuberculosis clone in Trinidad and Tobago. Infect Genet Evol. 2009, 9: 1336-1344. 10.1016\/j.meegid.2009.09.006.","journal-title":"Infect Genet Evol"},{"key":"6040_CR12","doi-asserted-by":"publisher","first-page":"e1000481","DOI":"10.1371\/journal.pcbi.1000481","volume":"5","author":"EC Berglund","year":"2009","unstructured":"Berglund EC, Nystedt B, Andersson SGE: Computational resources in infectious disease: limitations and challenges. PLoS Comp Biol. 2009, 5: e1000481-10.1371\/journal.pcbi.1000481.","journal-title":"PLoS Comp Biol"},{"key":"6040_CR13","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1016\/j.meegid.2010.07.006","volume":"10","author":"E Abadia","year":"2010","unstructured":"Abadia E, Zhang J, Vultos dos T, Ritacco V, Kremer K, Aktas E, Matsumoto T, Refregier G, van Soolingen D, Gicquel B, Sola C: Resolving lineage assignation on Mycobacterium tuberculosis clinical isolates classified by spoligotyping with a new high-throughput 3R SNPs based method. Infect Genet Evol. 2010, 10: 1066-1074. 10.1016\/j.meegid.2010.07.006.","journal-title":"Infect Genet Evol"},{"key":"6040_CR14","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/1471-2180-6-23","volume":"6","author":"K Brudey","year":"2006","unstructured":"Brudey K, Driscoll J, Rigouts L, Prodinger W, Gori A, Al-Hajoj S, Allix C, Aristimu\u00f1o L, Arora J, Baumanis V: Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology. BMC Microbiol. 2006, 6: 23-10.1186\/1471-2180-6-23.","journal-title":"BMC Microbiol"},{"key":"6040_CR15","doi-asserted-by":"publisher","first-page":"W326","DOI":"10.1093\/nar\/gkq351","volume":"38","author":"T Weniger","year":"2010","unstructured":"Weniger T, Krawczyk J, Supply P, Niemann S, Harmsen D: MIRU-VNTRplus: a web tool for polyphasic genotyping of Mycobacterium tuberculosis complex bacteria. Nucleic Acids Res. 2010, 38: W326-W331. 10.1093\/nar\/gkq351.","journal-title":"Nucleic Acids Res"},{"key":"6040_CR16","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1016\/j.meegid.2012.02.004","volume":"12","author":"C Demay","year":"2012","unstructured":"Demay C, Liens B, Burgui\u00e8re T, Hill V, Couvin D, Millet J, Mokrousov I, Sola C, Zozio T, Rastogi N: SITVITWEB-a publicly available international multimarker database for studying Mycobacterium tuberculosis genetic diversity and molecular epidemiology. Infect Genet Evol. 2012, 12: 755-766. 10.1016\/j.meegid.2012.02.004.","journal-title":"Infect Genet Evol"},{"key":"6040_CR17","doi-asserted-by":"publisher","first-page":"W728","DOI":"10.1093\/nar\/gki415","volume":"33","author":"DM Aanensen","year":"2005","unstructured":"Aanensen DM, Spratt BG: The multilocus sequence typing network: mlst.net. Nucleic Acids Res. 2005, 33: W728-W733. 10.1093\/nar\/gki415.","journal-title":"Nucleic Acids Res"},{"key":"6040_CR18","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1186\/1471-2105-5-86","volume":"5","author":"KA Jolley","year":"2004","unstructured":"Jolley KA, Chan M-S, Maiden MCJ: mlstdbNet - distributed multi-locus sequence typing (MLST) databases. BMC Bioinforma. 2004, 5: 86-10.1186\/1471-2105-5-86.","journal-title":"BMC Bioinforma"},{"key":"6040_CR19","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/1471-2334-7-32","volume":"7","author":"A Amadoz","year":"2007","unstructured":"Amadoz A, Gonz\u00e1lez-Candelas F: epiPATH: an information system for the storage and management of molecular epidemiology data from infectious pathogens. BMC Infect Dis. 2007, 7: 32-10.1186\/1471-2334-7-32.","journal-title":"BMC Infect Dis"},{"key":"6040_CR20","volume-title":"SNP typing reveals similarity in Mycobacterium tuberculosis genetic diversity between Portugal and Northeast Brazil","author":"JS Lopes","year":"2013","unstructured":"Lopes JS, Marques I, Soares P, Nebenzahl-Guimaraes H, Costa J, Miranda A, Duarte R, Alves A, Macedo R, Duarte TA, Barbosa T, Oliveira M, Nery JS, Boechat N, Pereira SM, Barreto ML, Pereira-Leal J, Gomes MGM, Penha-Goncalves C: SNP typing reveals similarity in Mycobacterium tuberculosis genetic diversity between Portugal and Northeast Brazil. 2013, Evol: Infect. Genet"},{"key":"6040_CR21","doi-asserted-by":"publisher","first-page":"W541","DOI":"10.1093\/nar\/gkr469","volume":"39","author":"PL Whetzel","year":"2011","unstructured":"Whetzel PL, Noy NF, Shah NH, Alexander PR, Nyulas C, Tudorache T, Musen MA: BioPortal: enhanced functionality via new Web services from the national center for biomedical ontology to access and use ontologies in software applications. Nucleic Acids Res. 2011, 39: W541-W545. 10.1093\/nar\/gkr469.","journal-title":"Nucleic Acids Res"},{"key":"6040_CR22","doi-asserted-by":"publisher","first-page":"e11147","DOI":"10.1371\/journal.pone.0011147","volume":"5","author":"AE Darling","year":"2010","unstructured":"Darling AE, Mau B, Perna NT: ProgressiveMauve: multiple genome alignment with gene gain. Loss and Rearrangement. PLoS ONE. 2010, 5: e11147-10.1371\/journal.pone.0011147.","journal-title":"Loss and Rearrangement. PLoS ONE"},{"key":"6040_CR23","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1128\/JB.188.2.759-772.2006","volume":"188","author":"I Filliol","year":"2005","unstructured":"Filliol I, Motiwala AS, Cavatore M, Qi W, Hazbon MH, Bobadilla delValle M, Fyfe J, Garcia-Garcia L, Rastogi N, Sola C, Zozio T, Guerrero MI, Leon CI, Crabtree J, Angiuoli S, Eisenach KD, Durmaz R, Joloba ML, Rendon A, Sifuentes-Osornio J, Ponce de Leon A, Cave MD, Fleischmann R, Whittam TS, Alland D: Global phylogeny of Mycobacterium tuberculosis based on Single Nucleotide Polymorphism (SNP) analysis: insights into tuberculosis evolution, phylogenetic accuracy of other DNA fingerprinting systems, and recommendations for a minimal standard SNP Set. J Bacteriol. 2005, 188: 759-772.","journal-title":"J Bacteriol"},{"key":"6040_CR24","doi-asserted-by":"publisher","first-page":"1758","DOI":"10.1128\/JCM.02255-09","volume":"48","author":"C Bouakaze","year":"2010","unstructured":"Bouakaze C, Keyser C, de Martino SJ, Sougakoff W, Veziris N, Dabernat H, Ludes B: Identification and genotyping of Mycobacterium tuberculosis complex species by Use of a SNaPshot minisequencing-based assay. J Clin Microbiol. 2010, 48: 1758-1766. 10.1128\/JCM.02255-09.","journal-title":"J Clin Microbiol"},{"key":"6040_CR25","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/978-1-59745-251-9_6","volume":"537","author":"S Guindon","year":"2009","unstructured":"Guindon S, Delsuc F, Dufayard J-F, Gascuel O: Estimating maximum likelihood phylogenies with PhyML. Methods Mol Biol. 2009, 537: 113-137. 10.1007\/978-1-59745-251-9_6.","journal-title":"Methods Mol Biol"},{"key":"6040_CR26","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1101\/gr.2289704","volume":"14","author":"ACE Darling","year":"2004","unstructured":"Darling ACE, Mau B, Blattner FR, Perna NT: Mauve: multiple alignment of conserved genomic sequence with rearrangements. Genome Res. 2004, 14: 1394-1403. 10.1101\/gr.2289704.","journal-title":"Genome Res"},{"key":"6040_CR27","unstructured":"BioNumerics, created by Applied Maths NV. Available from http:\/\/www.applied-maths.com"},{"key":"6040_CR28","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.tree.2004.03.015","volume":"19","author":"ORP Bininda-Emonds","year":"2004","unstructured":"Bininda-Emonds ORP: The evolution of supertrees. Trends Ecol Evol. 2004, 19: 315-322. 10.1016\/j.tree.2004.03.015.","journal-title":"Trends Ecol Evol"},{"key":"6040_CR29","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1146\/annurev.ecolsys.33.010802.150511","volume":"33","author":"ORP Bininda-Emonds","year":"2002","unstructured":"Bininda-Emonds ORP, Gittleman JL, Steel MA: THE (SUPER)TREE OF LIFE: procedures, problems, and prospects. Annu Rev Ecol Syst. 2002, 33: 265-289. 10.1146\/annurev.ecolsys.33.010802.150511.","journal-title":"Annu Rev Ecol Syst"},{"key":"6040_CR30","first-page":"249","volume-title":"Proceedings of the SIGCHI Conference on Human Factors in Computing Systems","author":"J Nielsen","year":"1990","unstructured":"Nielsen J, Molich R: Heuristic evaluation of user interfaces. Proceedings of the SIGCHI Conference on Human Factors in Computing Systems. 1990, Seattle, Washington, USA: ACM, 249-256."}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-14-264.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T01:14:01Z","timestamp":1630545241000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-14-264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8,30]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["6040"],"URL":"https:\/\/doi.org\/10.1186\/1471-2105-14-264","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8,30]]},"assertion":[{"value":"6 September 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"264"}}