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Pacific Northwest National Laboratory"},{"name":"Battelle Memorial Institute for the U.S. Department of Energy","award":["DE-AC05-76RLO-1830"],"award-info":[{"award-number":["DE-AC05-76RLO-1830"]}]},{"name":"EMSL"},{"name":"U.S. Department of Energy (DOE) Office of Biological and Environmental Research"},{"name":"NIH Institute of General Medical Sciences","award":["GM 103493-11"],"award-info":[{"award-number":["GM 103493-11"]}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:p>There are several notable challenges inherent for fully characterizing the entirety of the human saliva proteome using bottom\u2010up approaches, including polymorphic isoforms, <jats:styled-content style=\"fixed-case\">PTM<\/jats:styled-content>s, unique splice variants, deletions, and truncations. To address these challenges, we have developed a top\u2010down based <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\/MS approach, which cataloged 20 major human salivary proteins with a total of 83 proteoforms, containing a broad range of <jats:styled-content style=\"fixed-case\">PTM<\/jats:styled-content>s. Among these proteins, several previously reported disease biomarker proteins were identified at the intact protein level, such as beta\u20102 microglobulin. In addition, intact glycosylated proteoforms of several saliva proteins were also characterized, including intact <jats:italic>N<\/jats:italic>\u2010glycosylated protein prolactin inducible protein and <jats:italic>O<\/jats:italic>\u2010glycosylated acidic protein rich protein. These characterized proteoforms constitute an intact saliva proteoform database, which was used for quantitative comparison of intact salivary proteoforms among six healthy individuals. Human parotid and submandibular\/sublingual gland secretion samples (2 \u03bcg of protein each) from six healthy individuals were compared using <jats:styled-content style=\"fixed-case\">RPLC<\/jats:styled-content> coupled with the 12<jats:styled-content style=\"fixed-case\">T FT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ICR<\/jats:styled-content> mass spectrometer. Significantly different proteoform profiles were resolved with high reproducibility between parotid secretion and submandibular\/sublingual glands. The results from this study provide further insight into the potential mechanisms of <jats:styled-content style=\"fixed-case\">PTM<\/jats:styled-content> pathways in oral glandular secretion, expanding our knowledge of this complex yet easily accessible fluid. Intact protein <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> approach presented herein can potentially be applied for rapid and accurate identification of biomarkers from only a few microliters of human glandular saliva.<\/jats:p>","DOI":"10.1002\/pmic.201300378","type":"journal-article","created":{"date-parts":[[2014,3,3]],"date-time":"2014-03-03T20:12:45Z","timestamp":1393877565000},"page":"1211-1222","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Quantitative analysis of human salivary gland\u2010derived intact proteome using top\u2010down mass spectrometry"],"prefix":"10.1002","volume":"14","author":[{"given":"Si","family":"Wu","sequence":"first","affiliation":[{"name":"Environmental Molecular Sciences Laboratory Pacific Northwest National Laboratories  Richland WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph N.","family":"Brown","sequence":"additional","affiliation":[{"name":"Biological Sciences Division Pacific Northwest National Laboratories  Richland WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikola","family":"Toli\u0107","sequence":"additional","affiliation":[{"name":"Environmental Molecular Sciences Laboratory Pacific Northwest National Laboratories  Richland WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Meng","sequence":"additional","affiliation":[{"name":"Computational Mathematics Division Pacific Northwest National Laboratories  Richland WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of BioHealth Informatics Indiana University\u2010Purdue University Indianapolis  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haizhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Environmental Molecular Sciences Laboratory Pacific Northwest National Laboratories  Richland WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Environmental Molecular Sciences Laboratory Pacific Northwest National Laboratories  Richland WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J.","family":"Moore","sequence":"additional","affiliation":[{"name":"Biological Sciences Division Pacific Northwest National Laboratories  Richland WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Pevzner","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering University of California, San Diego  La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Smith","sequence":"additional","affiliation":[{"name":"Biological Sciences Division Pacific Northwest National Laboratories  Richland WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ljiljana","family":"Pa\u0161a\u2010Toli\u0107","sequence":"additional","affiliation":[{"name":"Environmental Molecular Sciences Laboratory Pacific Northwest National Laboratories  Richland WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,4,13]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"903","article-title":"The application of saliva, sweat and tear fluid for diagnostic purposes","volume":"51","author":"Haeckel R.","year":"1993","journal-title":"Ann. 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