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Review
. 2015 Jun;12(3):235-53.
doi: 10.1586/14789450.2015.1042867. Epub 2015 May 8.

Current strategies and findings in clinically relevant post-translational modification-specific proteomics

Oliver Pagel  1 , Stefan Loroch, Albert Sickmann, René P Zahedi
Affiliations
Review

Current strategies and findings in clinically relevant post-translational modification-specific proteomics

Oliver Pagel et al. Expert Rev Proteomics. 2015 Jun.

Abstract

Mass spectrometry-based proteomics has considerably extended our knowledge about the occurrence and dynamics of protein post-translational modifications (PTMs). So far, quantitative proteomics has been mainly used to study PTM regulation in cell culture models, providing new insights into the role of aberrant PTM patterns in human disease. However, continuous technological and methodical developments have paved the way for an increasing number of PTM-specific proteomic studies using clinical samples, often limited in sample amount. Thus, quantitative proteomics holds a great potential to discover, validate and accurately quantify biomarkers in body fluids and primary tissues. A major effort will be to improve the complete integration of robust but sensitive proteomics technology to clinical environments. Here, we discuss PTMs that are relevant for clinical research, with a focus on phosphorylation, glycosylation and proteolytic cleavage; furthermore, we give an overview on the current developments and novel findings in mass spectrometry-based PTM research.

Keywords: ERLIC; LC-MS; PTM; biomarkers; clinical proteomics; degradomics; glycoproteomics; phosphoproteomics; quantification.

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Figures

Figure 1.
Figure 1.
Frequently reported post-translational protein modifications.
Figure 2.
Figure 2.
Frequency of human PTMs. Summary of human PTMs which, according to UniProt and PhosphoSitePlus, have been detected (A) frequently, (B) less frequently and (C) rarely. For UniProt, the percentage of entries with experimental evidence is given (ECO:0000269). (D) The high number of known PTMs is in stark contrast to the limited knowledge about their involvement in disease.PTM: Post-translational modification.
Figure 3.
Figure 3.
Using the classical t-test for biomarker research. Two simulated markers 1 and 2 (A) in a background of an iTRAQ-based phosphoproteomics experiment (B, C). Using the two-sample t-test, the not-promising marker 2 would be defined as significant, whereas marker 1 would not be considered. Using the moderated t-test provided in the Limma package , only the promising marker 1 remains significant. A detailed description for the use of this package was recently published by Kammers et al. .
Figure 4.
Figure 4.
Protein copy number distribution in HeLa cells and copy numbers of some prominent cancer biomarkers. (*indicates a membrane protein). Dashed lines give the limits of detection when analyzing a certain number of cells, assuming a full quantitative recovery and a limit of detection of 100 amol. If only 600 cells are available, approximately 20% of the proteome will be covered.
See this image and copyright information in PMC

References

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