title: Large-scale inference of protein tissue origin in gram-positive sepsis plasma using quantitative targeted proteomics.
abstract: The plasma proteome is highly dynamic and variable, composed of proteins derived from surrounding tissues and cells. To investigate the complex processes that control the composition of the plasma proteome, we developed a mass spectrometry-based proteomics strategy to infer the origin of proteins detected in murine plasma. The strategy relies on the construction of a comprehensive protein tissue atlas from cells and highly vascularized organs using shotgun mass spectrometry. The protein tissue atlas was transformed to a spectral library for highly reproducible quantification of tissue-specific proteins directly in plasma using SWATH-like data-independent mass spectrometry analysis. We show that the method can determine drastic changes of tissue-specific protein profiles in blood plasma from mouse animal models with sepsis. The strategy can be extended to several other species advancing our understanding of the complex processes that contribute to the plasma proteome dynamics.
authors.affiliation: Department of Clinical Sciences, Lund, Division of Infection Medicine, Lund University, BMC, Tornavägen 10, SE-22184 Lund, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Malmström
authors.affiliation: Department of Clinical Sciences, Lund, Division of Infection Medicine, Lund University, BMC, Tornavägen 10, SE-22184 Lund, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Kilsgård
authors.affiliation: Department of Clinical Sciences, Lund, Division of Infection Medicine, Lund University, BMC, Tornavägen 10, SE-22184 Lund, Sweden.
authors.forename: Simon
authors.initials: S
authors.lastname: Hauri
authors.affiliation: Department of Clinical Sciences, Lund, Division of Infection Medicine, Lund University, BMC, Tornavägen 10, SE-22184 Lund, Sweden.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Smeds
authors.affiliation: Department of Clinical Sciences, Lund, Division of Infection Medicine, Lund University, BMC, Tornavägen 10, SE-22184 Lund, Sweden.
authors.forename: Heiko
authors.identifier: http://orcid.org/0000-0002-8111-2842
authors.initials: H
authors.lastname: Herwald
authors.affiliation: S3IT, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Lars
authors.initials: L
authors.lastname: Malmström
authors.affiliation: Department of Clinical Sciences, Lund, Division of Infection Medicine, Lund University, BMC, Tornavägen 10, SE-22184 Lund, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Malmström
mesh_terms: D000818:Animals; D015415:Biomarkers; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D010949:Plasma / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry / Q000145:classification* / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D018805:Sepsis / Q000097:blood* / Q000382:microbiology; D013290:Streptococcal Infections / Q000097:blood* / Q000382:microbiology; D013297:Streptococcus pyogenes
chemical_list: D015415:Biomarkers; D011506:Proteins