title: Discovery of putative salivary biomarkers for Sjögren's syndrome using high resolution mass spectrometry and bioinformatics.
abstract: The purpose of the current study was to determine if saliva contains biomarkers that can be used as diagnostic tools for Sjögren's syndrome (SjS). Twenty seven SjS patients and 27 age-matched healthy controls were recruited for these studies. Unstimulated glandular saliva was collected from the Wharton's duct using a suction device. Two µl of salvia were processed for mass spectrometry analyses on a prOTOF 2000 matrix-assisted laser desorption/ionization orthogonal time of flight (MALDI O-TOF) mass spectrometer. Raw data were analyzed using bioinformatic tools to identify biomarkers. MALDI O-TOF MS analyses of saliva samples were highly reproducible and the mass spectra generated were very rich in peptides and peptide fragments in the 750-7,500 Da range. Data analysis using bioinformatic tools resulted in several classification models being built and several biomarkers identified. One model based on 7 putative biomarkers yielded a sensitivity of 97.5%, specificity of 97.8% and an accuracy of 97.6%. One biomarker was present only in SjS samples and was identified as a proteolytic peptide originating from human basic salivary proline-rich protein 3 precursor. We conclude that salivary biomarkers detected by high-resolution mass spectrometry coupled with powerful bioinformatic tools offer the potential to serve as diagnostic/prognostic tools for SjS.
authors.affiliation: Department of General Dentistry, Tufts University School of Dental Medicine, Boston, MA 02111, USA. driss.zoukhri@tufts.edu
authors.forename: Driss
authors.initials: D
authors.lastname: Zoukhri
authors.forename: Ian
authors.initials: I
authors.lastname: Rawe
authors.forename: Mabi
authors.initials: M
authors.lastname: Singh
authors.forename: Ashley
authors.initials: A
authors.lastname: Brown
authors.forename: Claire L
authors.initials: CL
authors.lastname: Kublin
authors.forename: Kevin
authors.initials: K
authors.lastname: Dawson
authors.forename: William F
authors.initials: WF
authors.lastname: Haddon
authors.forename: Earl L
authors.initials: EL
authors.lastname: White
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Hanley
authors.forename: Daniel
authors.initials: D
authors.lastname: Tusé
authors.forename: Wasyl
authors.initials: W
authors.lastname: Malyj
authors.forename: Athena
authors.initials: A
authors.lastname: Papas
mesh_terms: D000368:Aged; D000465:Algorithms; D000595:Amino Acid Sequence; D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D048048:Dental Informatics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000032:analysis; D015203:Reproducibility of Results; D012463:Saliva / Q000737:chemistry*; D055273:Salivary Proline-Rich Proteins / Q000032:analysis*; D012680:Sensitivity and Specificity; D012859:Sjogren's Syndrome / Q000175:diagnosis* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013363:Submandibular Gland / Q000378:metabolism
chemical_list: D015415:Biomarkers; D011498:Protein Precursors; D055273:Salivary Proline-Rich Proteins