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bioRxiv · 10.1101/2020.08.04.236356

Multi-platforms approach for plasma proteomics: complementarity of Olink PEA technology to mass spectrometry-based protein profiling

Petrera, A.·von Toerne, C.·Behler, J.·Huth, C.·Thorand, B.·Hilgendorff, A.·Hauck, S. M.
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Abstract

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 structural 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 Assays (PEA). In order to address relevant differences and important shared characteristics, we tested the performance of LC-MS/MS in data-dependent and -independent acquisition modes and PEA Olink 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. In a next step, 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 prove their complementary strengths. We demonstrated a significant gain in proteome coverage depth and subsequent biological insight by platforms combination - a promising approach for future biomarker and mechanistic studies.

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Petrera, A., von Toerne, C., Behler, J., Huth, C., Thorand, B., Hilgendorff, A., Hauck, S. M.. 2020-08-06. Multi-platforms approach for plasma proteomics: complementarity of Olink PEA technology to mass spectrometry-based protein profiling. https://doi.org/10.1101/2020.08.04.236356

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