title: Comprehensive identification of proteins from MALDI imaging.
abstract: Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is a powerful tool for the visualization of proteins in tissues and has demonstrated considerable diagnostic and prognostic value. One main challenge is that the molecular identity of such potential biomarkers mostly remains unknown. We introduce a generic method that removes this issue by systematically identifying the proteins embedded in the MALDI matrix using a combination of bottom-up and top-down proteomics. The analyses of ten human tissues lead to the identification of 1400 abundant and soluble proteins constituting the set of proteins detectable by MALDI IMS including >90% of all IMS biomarkers reported in the literature. Top-down analysis of the matrix proteome identified 124 mostly N- and C-terminally fragmented proteins indicating considerable protein processing activity in tissues. All protein identification data from this study as well as the IMS literature has been deposited into MaTisse, a new publically available database, which we anticipate will become a valuable resource for the IMS community.
authors.affiliation: Chair for Proteomics and Bioanalytics, Technische Universität München, Emil Erlenmeyer Forum 5, 85354 Freising, Germany;
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Maier
authors.forename: Hannes
authors.initials: H
authors.lastname: Hahne
authors.forename: Amin Moghaddas
authors.initials: AM
authors.lastname: Gholami
authors.forename: Benjamin
authors.initials: B
authors.lastname: Balluff
authors.forename: Stephan
authors.initials: S
authors.lastname: Meding
authors.forename: Cédrik
authors.initials: C
authors.lastname: Schoene
authors.forename: Axel K
authors.initials: AK
authors.lastname: Walch
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kuster
mesh_terms: D000236:Adenoma / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001859:Bone Neoplasms / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism; D002853:Chromatography, Liquid; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism; D004947:Esophagus / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D012516:Osteosarcoma / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D011506:Proteins; D020543:Proteome