Recent Developments in Clinical Plasma Proteomics—Applied to Cardiovascular Research

The human plasma proteome mirrors the physiological state of the cardiovascular system, a fact that has been used to analyze plasma biomarkers in routine analysis for the diagnosis and monitoring of cardiovascular diseases for decades. These biomarkers address, however, only a very limited subset of cardiovascular diseases, such as acute myocardial infarct or acute deep vein thrombosis, and clinical plasma biomarkers for the diagnosis and stratification cardiovascular diseases that are growing in incidence, such as heart failure and abdominal aortic aneurysm, do not exist and are urgently needed. The discovery of novel biomarkers in plasma has been hindered by the complexity of the human plasma proteome that again transforms into an extreme analytical complexity when it comes to the discovery of novel plasma biomarkers. This complexity is, however, addressed by recent achievements in technologies for analyzing the human plasma proteome, thereby facilitating the possibility for novel biomarker discoveries. The aims of this article is to provide an overview of the recent achievements in technologies for proteomic analysis of the human plasma proteome and their applications in cardiovascular medicine.

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Faculty Opinions recommendation of Undulating changes in human plasma proteome profiles across the lifespan.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.737033740.793570208 ◽

2020 ◽

Author(s):

Shinya Kuroda ◽

Suguru Fujita

Keyword(s):

Human Plasma ◽

Plasma Proteome ◽

Human Plasma Proteome

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Detectability of Plasma Proteins in SRM Measurements

Current Proteomics ◽

10.2174/1570164615666180718151135 ◽

2018 ◽

Vol 16 (1) ◽

pp. 74-81 ◽

Cited By ~ 1

Author(s):

Olga I. Kiseleva ◽

Elena A. Ponomarenko ◽

Yulia A. Romashova ◽

Ekaterina V. Poverennaya ◽

Andrey V. Lisitsa

Keyword(s):

Blood Plasma ◽

Human Plasma ◽

Limit Of Detection ◽

Human Blood Plasma ◽

Analytical Sensitivity ◽

Plasma Proteome ◽

Protein Targets ◽

Blood Plasma Sample ◽

Specificity And Sensitivity ◽

Human Plasma Proteome

Background: Liquid chromatography coupled with targeted mass spectrometry underwent rapid technical evolution during last years and has become widely used technology in clinical laboratories. It offers confident specificity and sensitivity superior to those of traditional immunoassays. However, due to controversial reports on reproducibility of SRM measurements, the prospects of clinical appliance of the method are worth discussing. Objective: The study was aimed at assessment of capabilities of SRM to achieve a thorough assembly of the human plasma proteome. Method: We examined set of 19 human blood plasma samples to measure 100 proteins, including FDA-approved biomarkers, via SRM-assay. Results: Out of 100 target proteins 43 proteins were confidently detected in at least two blood plasma sample runs, 36 and 21 proteins were either not detected in any run or inconsistently detected, respectively. Empiric dependences on protein detectability were derived to predict the number of biological samples required to detect with certainty a diagnostically relevant quantum of the human plasma proteome. Conclusion: The number of samples exponentially increases with an increase in the number of protein targets, while proportionally decreasing to the logarithm of the limit of detection. Analytical sensitivity and enormous proteome heterogeneity are major bottlenecks of the human proteome exploration.

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