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.
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Objective: The study was aimed at assessment of capabilities of SRM to achieve a thorough assembly
of the human plasma proteome.
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Method: We examined set of 19 human blood plasma samples to measure 100 proteins, including
FDA-approved biomarkers, via SRM-assay.
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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.
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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.
The Human Plasma Proteome: History, Character, and Diagnostic Prospects: Fig. 3.
