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Multiplatform approach for plasma proteomics: Complementarity of olink proximity extension assay technology to mass spectrometry-based protein profiling.
J. Proteome Res. 20, 751-762 (2021)
The plasma proteome is the ultimate target for biomarker discovery. It stores an endless amount of information on the pathophysiological status of a living organism, which is, however, still difficult to comprehensively access. The high complexity of the plasma proteome can be addressed by either a system-wide and unbiased tool such as mass spectrometry (LC-MS/MS) or a highly sensitive targeted immunoassay such as the proximity extension assay (PEA). To address relevant differences and important shared characteristics, we tested the performance of LC-MS/MS in the data-dependent and data-independent acquisition modes and Olink PEA to measure circulating plasma proteins in 173 human plasma samples from a Southern German population-based cohort. We demonstrated the measurement of more than 300 proteins with both LC-MS/MS approaches applied, mainly including high-abundance plasma proteins. By the use of the PEA technology, we measured 728 plasma proteins, covering a broad dynamic range with high sensitivity down to pg/mL concentrations. Then, we quantified 35 overlapping proteins with all three analytical platforms, verifying the reproducibility of data distributions, measurement correlation, and gender-based differential expression. Our work highlights the limitations and the advantages of both targeted and untargeted approaches and proves their complementary strengths. We demonstrated a significant gain in proteome coverage depth and subsequent biological insight by a combination of platforms - a promising approach for future biomarker and mechanistic studies.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Complementarity ; Immunoassays ; Mass Spectrometry ; Plasma ; Proteomics; Sex-differences; Biomarkers; Workflow
ISSN (print) / ISBN
1535-3893
e-ISSN
1535-3907
Zeitschrift
Journal of Proteome Research
Quellenangaben
Band: 20,
Heft: 1,
Seiten: 751-762
Verlag
American Chemical Society (ACS)
Verlagsort
1155 16th St, Nw, Washington, Dc 20036 Usa
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
CF Metabolomics & Proteomics (CF-MPC)
Institute of Epidemiology II (EPI2)
Lung Health and Immunity (LHI)
Institute of Epidemiology II (EPI2)
Lung Health and Immunity (LHI)
Förderungen
Helmholtz Zentrum Munchen-German Research Center for Environmental Health - German Federal Ministry of Education and Research (BMBF)
State of Bavaria
Munich Center of Health Sciences (MC-Health), LudwigMaximilians-Universitat Munchen, as part of LMUinnovativ
State of Bavaria
Munich Center of Health Sciences (MC-Health), LudwigMaximilians-Universitat Munchen, as part of LMUinnovativ