{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:55:10Z","timestamp":1789638910880,"version":"4.0.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T00:00:00Z","timestamp":1481760000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T00:00:00Z","timestamp":1481760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study on interstitial cystitis (IC) aims to identify a unique urine metabolomic profile associated with IC, which can be defined as an unpleasant sensation including pain and discomfort related to the urinary bladder, without infection or other identifiable causes. Although the burden of IC on the American public is immense in both human and financial terms, there is no clear diagnostic test for IC, but rather it is a disease of exclusion. Very little is known about the clinically useful urinary biomarkers of IC, which are desperately needed. Untargeted comprehensive metabolomic profiling was performed using gas-chromatography\/mass-spectrometry to compare urine specimens of IC patients or health donors. The study profiled 200 known and 290 unknown metabolites. The majority of the thirty significantly changed metabolites before false discovery rate correction were unknown compounds. Partial least square discriminant analysis clearly separated IC patients from controls. The high number of unknown compounds hinders useful biological interpretation of such predictive models. Given that urine analyses have great potential to be adapted in clinical practice, research has to be focused on the identification of unknown compounds to uncover important clues about underlying disease mechanisms.<\/jats:p>","DOI":"10.1038\/srep39227","type":"journal-article","created":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T13:03:29Z","timestamp":1481807009000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Interstitial Cystitis-Associated Urinary Metabolites Identified by Mass-Spectrometry Based Metabolomics Analysis"],"prefix":"10.1038","volume":"6","author":[{"given":"Tobias","family":"Kind","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunho","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeeun D.","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenqiu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tack","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Fiehn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayoung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,12,15]]},"reference":[{"key":"BFsrep39227_CR1","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.juro.2011.03.132","volume":"186","author":"SH Berry","year":"2011","unstructured":"Berry, S. H. et al. Prevalence of symptoms of bladder pain syndrome\/interstitial cystitis among adult females in the United States. The Journal of urology 186, 540\u2013544, doi: 10.1016\/j.juro.2011.03.132 (2011).","journal-title":"The Journal of urology"},{"key":"BFsrep39227_CR2","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.1016\/j.juro.2011.03.064","volume":"185","author":"PM Hanno","year":"2011","unstructured":"Hanno, P. M. et al. AUA guideline for the diagnosis and treatment of interstitial cystitis\/bladder pain syndrome. The Journal of urology 185, 2162\u20132170, doi: 10.1016\/j.juro.2011.03.064 (2011).","journal-title":"The Journal of urology"},{"key":"BFsrep39227_CR3","doi-asserted-by":"publisher","first-page":"2464","DOI":"10.1016\/j.juro.2012.09.081","volume":"188","author":"JC Winters","year":"2012","unstructured":"Winters, J. C. et al. Urodynamic studies in adults: AUA\/SUFU guideline. The Journal of urology 188, 2464\u20132472, doi: 10.1016\/j.juro.2012.09.081 (2012).","journal-title":"The Journal of urology"},{"key":"BFsrep39227_CR4","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1007\/s00192-005-1301-x","volume":"16","author":"P Hanno","year":"2005","unstructured":"Hanno, P., Keay, S., Moldwin, R. & Van Ophoven, A. International Consultation on IC - Rome, September 2004\/Forging an International Consensus: progress in painful bladder syndrome\/interstitial cystitis. Report and abstracts. International urogynecology journal and pelvic floor dysfunction 16 Suppl 1, S2\u2013S34, doi: 10.1007\/s00192-005-1301-x (2005).","journal-title":"International urogynecology journal and pelvic floor dysfunction"},{"key":"BFsrep39227_CR5","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/j.urology.2009.06.078","volume":"74","author":"JQ Clemens","year":"2009","unstructured":"Clemens, J. Q. et al. Validation of a modified National Institutes of Health chronic prostatitis symptom index to assess genitourinary pain in both men and women. Urology 74, 983\u2013987, quiz 987 e981\u2013983, doi: 10.1016\/j.urology.2009.06.078 (2009).","journal-title":"Urology"},{"key":"BFsrep39227_CR6","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1016\/j.juro.2016.04.070","volume":"196","author":"AJ Stephens-Shields","year":"2016","unstructured":"Stephens-Shields, A. J. et al. Symptom Variability and Early Symptom Regression in the MAPP Study: A Prospective Study of Urological Chronic Pelvic Pain Syndrome. The Journal of urology 196, 1450\u20131455, doi: 10.1016\/j.juro.2016.04.070 (2016).","journal-title":"The Journal of urology"},{"key":"BFsrep39227_CR7","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.ygyno.2015.08.026","volume":"139","author":"Z Liu","year":"2015","unstructured":"Liu, Z. et al. Suboptimal cytoreduction in ovarian carcinoma is associated with molecular pathways characteristic of increased stromal activation. Gynecologic oncology 139, 394\u2013400, doi: 10.1016\/j.ygyno.2015.08.026 (2015).","journal-title":"Gynecologic oncology"},{"key":"BFsrep39227_CR8","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1093\/bioinformatics\/btu778","volume":"31","author":"Z Liu","year":"2015","unstructured":"Liu, Z., Sun, F., Braun, J., McGovern, D. P. & Piantadosi, S. Multilevel regularized regression for simultaneous taxa selection and network construction with metagenomic count data. Bioinformatics 31, 1067\u20131074, doi: 10.1093\/bioinformatics\/btu778 (2015).","journal-title":"Bioinformatics"},{"key":"BFsrep39227_CR9","doi-asserted-by":"publisher","first-page":"6306","DOI":"10.1002\/anie.201300158","volume":"52","author":"S Grimme","year":"2013","unstructured":"Grimme, S. Towards first principles calculation of electron impact mass spectra of molecules. Angewandte Chemie 52, 6306\u20136312, doi: 10.1002\/anie.201300158 (2013).","journal-title":"Angewandte Chemie"},{"key":"BFsrep39227_CR10","doi-asserted-by":"publisher","first-page":"7689","DOI":"10.1021\/acs.analchem.6b01622","volume":"88","author":"F Allen","year":"2016","unstructured":"Allen, F., Pon, A., Greiner, R. & Wishart, D. Computational Prediction of Electron Ionization Mass Spectra to Assist in GC\/MS Compound Identification. Analytical chemistry 88, 7689\u20137697, doi: 10.1021\/acs.analchem.6b01622 (2016).","journal-title":"Analytical chemistry"},{"key":"BFsrep39227_CR11","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s13321-015-0087-1","volume":"7","author":"JG Jeffryes","year":"2015","unstructured":"Jeffryes, J. G. et al. MINEs: open access databases of computationally predicted enzyme promiscuity products for untargeted metabolomics. Journal of cheminformatics 7, 44, doi: 10.1186\/s13321-015-0087-1 (2015).","journal-title":"Journal of cheminformatics"},{"key":"BFsrep39227_CR12","doi-asserted-by":"publisher","first-page":"358184","DOI":"10.1155\/2012\/358184","volume":"2012","author":"J Lv","year":"2012","unstructured":"Lv, J. et al. MCP-1-induced histamine release from mast cells is associated with development of interstitial cystitis\/bladder pain syndrome in rat models. Mediators of inflammation 2012, 358184, doi: 10.1155\/2012\/358184 (2012).","journal-title":"Mediators of inflammation"},{"key":"BFsrep39227_CR13","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1046\/j.0014-2956.2002.02626.x","volume":"269","author":"S Erickson","year":"2002","unstructured":"Erickson, S. et al. Interferon-alpha inhibits Stat5 DNA-binding in IL-2 stimulated primary T-lymphocytes. European journal of biochemistry\/FEBS 269, 29\u201337 (2002).","journal-title":"European journal of biochemistry\/FEBS"},{"key":"BFsrep39227_CR14","doi-asserted-by":"publisher","first-page":"3806","DOI":"10.1016\/j.jchromb.2009.09.025","volume":"877","author":"Y Fukui","year":"2009","unstructured":"Fukui, Y., Kato, M., Inoue, Y., Matsubara, A. & Itoh, K. A metabonomic approach identifies human urinary phenylacetylglutamine as a novel marker of interstitial cystitis. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 877, 3806\u20133812, doi: 10.1016\/j.jchromb.2009.09.025 (2009).","journal-title":"Journal of chromatography. B, Analytical technologies in the biomedical and life sciences"},{"key":"BFsrep39227_CR15","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1016\/j.urology.2006.04.033","volume":"68","author":"LM Lamale","year":"2006","unstructured":"Lamale, L. M., Lutgendorf, S. K., Zimmerman, M. B. & Kreder, K. J. Interleukin-6, histamine, and methylhistamine as diagnostic markers for interstitial cystitis. Urology 68, 702\u2013706, doi: 10.1016\/j.urology.2006.04.033 (2006).","journal-title":"Urology"},{"key":"BFsrep39227_CR16","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1021\/pr5007729","volume":"14","author":"H Wen","year":"2015","unstructured":"Wen, H. et al. Urinary metabolite profiling combined with computational analysis predicts interstitial cystitis-associated candidate biomarkers. Journal of proteome research 14, 541\u2013548, doi: 10.1021\/pr5007729 (2015).","journal-title":"Journal of proteome research"},{"key":"BFsrep39227_CR17","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.ebiom.2016.03.040","volume":"7","author":"KS Parker","year":"2016","unstructured":"Parker, K. S. et al. Urinary Metabolomics Identifies a Molecular Correlate of Interstitial Cystitis\/Bladder Pain Syndrome in a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Cohort. EBioMedicine 7, 167\u2013174, doi: 10.1016\/j.ebiom.2016.03.040 (2016).","journal-title":"EBioMedicine"},{"key":"BFsrep39227_CR18","doi-asserted-by":"publisher","first-page":"e73076","DOI":"10.1371\/journal.pone.0073076","volume":"8","author":"S Bouatra","year":"2013","unstructured":"Bouatra, S. et al. The human urine metabolome. PloS one 8, e73076, doi: 10.1371\/journal.pone.0073076 (2013).","journal-title":"PloS one"},{"key":"BFsrep39227_CR19","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.ab.2007.01.028","volume":"363","author":"T Kind","year":"2007","unstructured":"Kind, T., Tolstikov, V., Fiehn, O. & Weiss, R. H. A comprehensive urinary metabolomic approach for identifying kidney cancerr. Analytical biochemistry 363, 185\u2013195, doi: 10.1016\/j.ab.2007.01.028 (2007).","journal-title":"Analytical biochemistry"},{"key":"BFsrep39227_CR20","doi-asserted-by":"publisher","first-page":"10038","DOI":"10.1021\/ac9019522","volume":"81","author":"T Kind","year":"2009","unstructured":"Kind, T. et al. FiehnLib: mass spectral and retention index libraries for metabolomics based on quadrupole and time-of-flight gas chromatography\/mass spectrometry. Analytical chemistry 81, 10038\u201310048, doi: 10.1021\/ac9019522 (2009).","journal-title":"Analytical chemistry"},{"key":"BFsrep39227_CR21","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1093\/bioinformatics\/btr392","volume":"27","author":"J Xia","year":"2011","unstructured":"Xia, J., Sinelnikov, I. V. & Wishart, D. S. MetATT: a web-based metabolomics tool for analyzing time-series and two-factor datasets. Bioinformatics 27, 2455\u20132456, doi: 10.1093\/bioinformatics\/btr392 (2011).","journal-title":"Bioinformatics"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep39227.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep39227","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep39227.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T02:54:40Z","timestamp":1672887280000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep39227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,15]]},"references-count":21,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep39227"],"URL":"https:\/\/doi.org\/10.1038\/srep39227","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,15]]},"assertion":[{"value":"22 August 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"39227"}}