Multiplatform Approach for Plasma Proteomics: Complementarity of Olink Proximity Extension Assay Technology to Mass Spectrometry-Based Protein Profiling

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...

Full description

Saved in:
Bibliographic Details
Published in:Journal of proteome research Vol. 20; no. 1; p. 751
Main Authors: Petrera, Agnese, von Toerne, Christine, Behler, Jennifer, Huth, Cornelia, Thorand, Barbara, Hilgendorff, Anne, Hauck, Stefanie M
Format: Journal Article
Language:English
Published: United States 01.01.2021
Subjects:
immunoassays
mass spectrometry
proteomics
plasma
complementarity
ISSN:1535-3907, 1535-3907
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1535-3907
1535-3907
DOI:10.1021/acs.jproteome.0c00641