Pre-Analytical and Analytical Variability in Absolute Quantitative Mrm-Based Plasma Proteomic Studies

Abstract

Quantitative plasma proteomics, through the use of targeted MRM-MS and isotopically labeled standards, is emerging as a popular technique to address biological- and biomedical-centered queries. High precision and accuracy are essential in such measurements, particularly in protein biomarker research where translation to the clinic is sought. Standardized procedures and routine performance evaluation of all stages of the workflow (both pre-analytical and analytical) are therefore imperative to satisfy these requisites and enable high inter-laboratory reproducibility and transferability. In this review, we first discuss the pre-analytical and analytical variables that can affect the precision and accuracy of ‘absolute’ quantitative plasma proteomic measurements. Proposed strategies to limit such variability will then be highlighted and unmet needs for future exploration will be noted. Although there is no way to conduct a truly comprehensive review on this broad, rapidly changing topic, we have highlighted key aspects and included references to review articles on various sub-topics.

Financial & competing interests disclosure

All authors are employees of the UVic-Genome BC Proteomics Centre. The authors would like to thank Genome Canada, Genome BC, and the Western Economic Diversification of Canada for platform funding and support. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was obtained in the preparation of this manuscript. No writing assistance was utilized in the production of this manuscript.

Notes

Reprinted and modified with permission from Table 1 in [53].

*Extended from Table 1 in [53].

Table 16.2 reproduced from [51] with permission.

Table 1 reproduced from [53] with permission, and extended.

*: From Table 1 in [52].