{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:14:08Z","timestamp":1788408848030,"version":"build-2803163510"},"reference-count":32,"publisher":"American Chemical Society (ACS)","issue":"1","license":[{"start":{"date-parts":[[2015,10,30]],"date-time":"2015-10-30T00:00:00Z","timestamp":1446163200000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI052473"],"award-info":[{"award-number":["R01AI052473"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U01AI088752"],"award-info":[{"award-number":["U01AI088752"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000061","name":"Fogarty International Center","doi-asserted-by":"publisher","award":["R01TW009504"],"award-info":[{"award-number":["R01TW009504"]}],"id":[{"id":"10.13039\/100000061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,1,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>With increasing efficiency, accuracy, and speed we can access complete genome sequences from thousands of infectious microorganisms; however, the ability to predict antigenic targets of the immune system based on amino acid sequence alone is still needed. Here we use a Leptospira interrogans microarray expressing 91% (3359) of all leptospiral predicted ORFs (3667) and make an empirical accounting of all antibody reactive antigens recognized in sera from naturally infected humans; 191 antigens elicited an IgM or IgG response, representing 5% of the whole proteome. We classified the reactive antigens into 26 annotated COGs (clusters of orthologous groups), 26 JCVI Mainrole annotations, and 11 computationally predicted proteomic features. Altogether, 14 significantly enriched categories were identified, which are associated with immune recognition including mass spectrometry evidence of in vitro expression and in vivo mRNA up-regulation. Together, this group of 14 enriched categories accounts for just 25% of the leptospiral proteome but contains 50% of the immunoreactive antigens. These findings are consistent with our previous studies of other Gram-negative bacteria. This genome-wide approach provides an empirical basis to predict and classify antibody reactive antigens based on structural, physical\u2013chemical, and functional proteomic features and a framework for understanding the breadth and specificity of the immune response to L. interrogans.<\/jats:p>","DOI":"10.1021\/pr500718t","type":"journal-article","created":{"date-parts":[[2014,10,30]],"date-time":"2014-10-30T17:07:51Z","timestamp":1414688871000},"page":"549-556","source":"Crossref","is-referenced-by-count":10,"title":["Proteomic Features Predict\nSeroreactivity against\nLeptospiral Antigens in Leptospirosis Patients"],"prefix":"10.1021","volume":"14","author":[{"given":"Carolina","family":"Lessa-Aquino","sequence":"first","affiliation":[{"name":"Brazilian Ministry of Health , , Avenida Brasil, 4365 - Manguinhos , , ,","place":["Rio de Janeiro, RJ, Brazil, 21040-900"]},{"name":"University of California Irvine , , 3221 McGaugh Hall , , ,","place":["Irvine, California, United States, 92697"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Elsio A.","family":"Wunder","sequence":"additional","affiliation":[{"name":"Yale School of Public Health , , 60 College Street , , ,","place":["New Haven, Connecticut, United States, 06520"]},{"name":"Brazilian Ministry of Health, Rua Waldemar Falca\u0303o, 121 - Candeal , , , ,","place":["Salvador, BA 40296-710, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet C.","family":"Lindow","sequence":"additional","affiliation":[{"name":"Yale School of Public Health , , 60 College Street , , ,","place":["New Haven, Connecticut, United States, 06520"]},{"name":"Brazilian Ministry of Health, Rua Waldemar Falca\u0303o, 121 - Candeal , , , ,","place":["Salvador, BA 40296-710, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila B.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Brazilian Ministry of Health , , Avenida Brasil, 4365 - Manguinhos , , ,","place":["Rio de Janeiro, RJ, Brazil, 21040-900"]},{"name":"University of California Irvine , , 3221 McGaugh Hall , , ,","place":["Irvine, California, United States, 92697"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozelyn","family":"Pablo","sequence":"additional","affiliation":[{"name":"University of California Irvine , , 3221 McGaugh Hall , , ,","place":["Irvine, California, United States, 92697"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Nakajima","sequence":"additional","affiliation":[{"name":"University of California Irvine , , 3221 McGaugh Hall , , ,","place":["Irvine, California, United States, 92697"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Algis","family":"Jasinskas","sequence":"additional","affiliation":[{"name":"University of California Irvine , , 3221 McGaugh Hall , , ,","place":["Irvine, California, United States, 92697"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Liang","sequence":"additional","affiliation":[{"name":"University of California Irvine , , 3221 McGaugh Hall , , ,","place":["Irvine, California, United States, 92697"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitermayer G.","family":"Reis","sequence":"additional","affiliation":[{"name":"Brazilian Ministry of Health, Rua Waldemar Falca\u0303o, 121 - Candeal , , , ,","place":["Salvador, BA 40296-710, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert I.","family":"Ko","sequence":"additional","affiliation":[{"name":"Yale School of Public Health , , 60 College Street , , ,","place":["New Haven, Connecticut, United States, 06520"]},{"name":"Brazilian Ministry of Health, Rua Waldemar Falca\u0303o, 121 - Candeal , , , ,","place":["Salvador, BA 40296-710, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco A.","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Brazilian Ministry of Health , , Avenida Brasil, 4365 - Manguinhos , , ,","place":["Rio de Janeiro, RJ, Brazil, 21040-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip L.","family":"Felgner","sequence":"additional","affiliation":[{"name":"University of California Irvine , , 3221 McGaugh Hall , , ,","place":["Irvine, California, United States, 92697"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,10,30]]},"reference":[{"issue":"2","key":"2026090223330425500_cit1","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1128\/CMR.14.2.296-326.2001","article-title":"Leptospirosis","volume":"14","author":"Levett","year":"2001","journal-title":"Clin. Microbiol. Rev."},{"issue":"5","key":"2026090223330425500_cit2","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1097\/01.qco.0000178824.05715.2c","article-title":"Leptospirosis","volume":"18","author":"McBride","year":"2005","journal-title":"Curr. Opin. Infect. Dis."},{"issue":"10","key":"2026090223330425500_cit3","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nrmicro2208","article-title":"Leptospira:\nthe dawn of the molecular\ngenetics era for an emerging zoonotic pathogen","volume":"7","author":"Ko","year":"2009","journal-title":"Nat. Rev. Microbiol"},{"issue":"3","key":"2026090223330425500_cit4","doi-asserted-by":"crossref","first-page":"505","DOI":"10.3201\/eid1403.071064","article-title":"Leptospirosis-associated severe pulmonary hemorrhagic syndrome, Salvador,\nBrazil","volume":"14","author":"Gouveia","year":"2008","journal-title":"Emerging Infect. Dis."},{"issue":"6","key":"2026090223330425500_cit5","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1086\/313501","article-title":"Acute lung injury in leptospirosis:\nclinical and laboratory features, outcome, and factors associated\nwith mortality","volume":"29","author":"Marotto","year":"1999","journal-title":"Clin. Infect. Dis."},{"issue":"5","key":"2026090223330425500_cit6","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1111\/j.1365-3083.2010.02505.x","article-title":"Leptospirosis:\naspects of innate\nimmunity, immunopathogenesis and immune evasion from the complement\nsystem","volume":"73","author":"Fraga","year":"2011","journal-title":"Scand. J. Immunol."},{"issue":"6","key":"2026090223330425500_cit7","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1089\/hyb.2008.0056","article-title":"Monoclonal antibodies to LipL32 protect\nagainst heterologous Leptospira spp. challenge","volume":"27","author":"Maneewatch","year":"2008","journal-title":"Hybridoma"},{"issue":"1","key":"2026090223330425500_cit8","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1017\/S0950268800048779","article-title":"Antigens recognized\nby the human immune response to severe leptospirosis in Barbados","volume":"107","author":"Chapman","year":"1991","journal-title":"Epidemiol. Infect."},{"issue":"2","key":"2026090223330425500_cit9","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1084\/jem.31.2.135","article-title":"Etiology of\nYellow Fever: X. Comparative Immunological Studies on Leptospira Icteroides\nand Leptospira IcterohaemoorrhagiaE","volume":"31","author":"Noguchi","year":"1920","journal-title":"J. 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Vaccine Immunol."},{"issue":"10","key":"2026090223330425500_cit14","doi-asserted-by":"crossref","first-page":"M110.006304","DOI":"10.1074\/mcp.M110.006304","article-title":"Profiling the humoral immune response of acute and\nchronic Q fever by protein microarray","volume":"10","author":"Vigil","year":"2011","journal-title":"Mol.\nCell. Proteomics"},{"issue":"9","key":"2026090223330425500_cit15","doi-asserted-by":"crossref","first-page":"M111.007948","DOI":"10.1074\/mcp.M111.007948","article-title":"Sterile\nprotective immunity to malaria is associated with a panel of novel\nP. falciparum antigens","volume":"10","author":"Trieu","year":"2011","journal-title":"Mol. Cell. 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Cell.\nProteomics"},{"issue":"10","key":"2026090223330425500_cit19","doi-asserted-by":"crossref","first-page":"4813","DOI":"10.1021\/pr200619r","article-title":"Systems biology approach predicts antibody signature\nassociated with Brucella melitensis infection in humans","volume":"10","author":"Liang","year":"2011","journal-title":"J. Proteome Res."},{"issue":"10","key":"2026090223330425500_cit20","doi-asserted-by":"crossref","first-page":"e2499","DOI":"10.1371\/journal.pntd.0002499","article-title":"Identification\nof\nseroreactive proteins of Leptospira interrogans serovar copenhageni\nusing a high-density protein microarray approach","volume":"7","author":"Lessa-Aquino","year":"2013","journal-title":"PLoS Neglected Trop. Dis."},{"issue":"22","key":"2026090223330425500_cit21","doi-asserted-by":"crossref","first-page":"6074","DOI":"10.1128\/JB.01119-12","article-title":"Leptospiral outer membrane protein\nmicroarray, a novel approach to identification of host ligand-binding\nproteins","volume":"194","author":"Pinne","year":"2012","journal-title":"J. Bacteriol."},{"issue":"5","key":"2026090223330425500_cit22","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1002\/cbdv.201100360","article-title":"Predicting antigenicity\nof proteins in a bacterial\nproteome; a protein microarray and nai\u0308ve Bayes classification\napproach","volume":"9","author":"Liang","year":"2012","journal-title":"Chem. Biodiversity"},{"issue":"3","key":"2026090223330425500_cit23","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1073\/pnas.0408782102","article-title":"Profiling the humoral immune response\nto infection\nby using proteome microarrays: high-throughput vaccine and diagnostic\nantigen discovery","volume":"102","author":"Davies","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U.\nS. A."},{"issue":"4","key":"2026090223330425500_cit24","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1046\/j.1365-2958.2003.03619.x","article-title":"Pathogenic Leptospira species express\nsurface-exposed proteins belonging to the bacterial immunoglobulin\nsuperfamily","volume":"49","author":"Matsunaga","year":"2003","journal-title":"Mol. Microbiol."},{"issue":"7256","key":"2026090223330425500_cit25","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/nature08184","article-title":"Proteome-wide\ncellular protein concentrations of the\nhuman pathogen Leptospira interrogans","volume":"460","author":"Malmstro\u0308m","year":"2009","journal-title":"Nature"},{"issue":"3","key":"2026090223330425500_cit26","doi-asserted-by":"crossref","first-page":"e1004004","DOI":"10.1371\/journal.ppat.1004004","article-title":"A model system for\nstudying the transcriptomic and physiological changes associated with\nmammalian host-adaptation by Leptospira interrogans serovar Copenhageni","volume":"10","author":"Caimano","year":"2014","journal-title":"PLoS Pathog."},{"issue":"7","key":"2026090223330425500_cit27","doi-asserted-by":"crossref","first-page":"e11447","DOI":"10.1371\/journal.pone.0011447","article-title":"Identification\nof the feline humoral immune response to Bartonella henselae infection\nby protein microarray","volume":"5","author":"Vigil","year":"2010","journal-title":"PLoS One"},{"issue":"8","key":"2026090223330425500_cit28","doi-asserted-by":"crossref","first-page":"3374","DOI":"10.1128\/IAI.00048-08","article-title":"A genome-wide proteome array reveals\na limited set of immunogens in natural infections of humans and white-footed\nmice with Borrelia burgdorferi","volume":"76","author":"Barbour","year":"2008","journal-title":"Infect. Immun."},{"issue":"32","key":"2026090223330425500_cit29","doi-asserted-by":"crossref","first-page":"13499","DOI":"10.1073\/pnas.0812080106","article-title":"A Burkholderia\npseudomallei protein microarray reveals serodiagnostic and cross-reactive\nantigens","volume":"106","author":"Felgner","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"9181","key":"2026090223330425500_cit30","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/S0140-6736(99)80012-9","article-title":"Urban epidemic\nof severe leptospirosis in Brazil. Salvador Leptospirosis Study Group","volume":"354","author":"Ko","year":"1999","journal-title":"Lancet"},{"issue":"1","key":"2026090223330425500_cit31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actatropica.2008.07.005","article-title":"Carriage of Leptospira interrogans among domestic rats\nfrom an urban setting highly endemic for leptospirosis in Brazil","volume":"108","author":"de Faria","year":"2008","journal-title":"Acta Trop"},{"issue":"23","key":"2026090223330425500_cit32","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1093\/bioinformatics\/btq551","article-title":"High-throughput prediction of protein\nantigenicity using protein microarray data","volume":"26","author":"Magnan","year":"2010","journal-title":"Bioinformatics"}],"container-title":["Journal of Proteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/pr500718t","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/14\/1\/549\/16228560\/pr500718t.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/14\/1\/549\/16228560\/pr500718t.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T03:34:08Z","timestamp":1788406448000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/14\/1\/549\/1518515\/Proteomic-Features-Predict-Seroreactivity-against"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,30]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2014,10,30]]},"published-print":{"date-parts":[[2015,1,2]]}},"URL":"https:\/\/doi.org\/10.1021\/pr500718t","relation":{},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,30]]}}}