Towards comprehensive and quantitative proteomics for diagnosis and therapy of human disease

Abstract

Given superior analytical features, mass spectrometry proteomics is well suited for the basic investigation and clinical diagnosis of human disease. Modern mass spectrometry enables detailed functional characterization of the pathogenic biochemical processes, as achieved by accurate and comprehensive quantification of proteins and their regulatory chemical modifications. Here, we describe how high-accuracy mass spectrometry in combination with high-resolution chromatographic separations can be leveraged to meet these analytical requirements in a mechanism-focused manner. We review the quantification methods capable of producing accurate measurements of protein abundance and post-translational modification stoichiometries. We then discuss how experimental design and chromatographic resolution can be leveraged to achieve comprehensive functional characterization of biochemical processes in complex biological proteomes. Finally, we describe current approaches for quantitative analysis of a common functional protein modification: reversible phosphorylation. In all, current instrumentation and methods of high-resolution chromatography and mass spectrometry proteomics are poised for immediate translation into improved diagnostic strategies for pediatric and adult diseases.

Proteomic profiling of the hypothalamus in two mouse models of narcolepsy

“…Despite the remarkable advances in quantitative proteomics , many limitations remain. One limitation is the coelution of low abundance peptides with high abundance peptides, which leads to ion suppression and an inability to detect the coeluting low abundance peptides.…”

“…Recent advances in quantitative proteomics have significantly improved protein profiling of complex systems . Label‐free quantification with LC‐MS/MS allows for the identification of hundreds of proteins, and facilitates quantitative comparisons of protein levels between samples and across groups .…”

Quantitative proteomics identified 3 oxidative phosphorylation genes with clinical prognostic significance in gastric cancer

“…Proteomics is considered as a state‐of‐the‐art, large‐scale and systematic analytic approach, enabling the identification and quantification of proteins in specific biological specimens 3 . Additionally, the difference between normal and lesion samples can be quantified using quantitative proteomics and this offers valuable evidence for identifying novel biomarkers and elucidating mechanisms underlying complicated biological processes 4 . A comprehensive molecular characterization of gastric adenocarcinoma has been studied in 2014 5 .…”

Exploration the mechanism of doxorubicin-induced Heart failure in Rats by integration of proteomics and metabolomics data

“…With the development of proteomics technology, tandem mass tag (TMT) labeling quantitative proteomics technology, as a novel quantitative method, can be used to quickly and quantitatively evaluate protein localization independent of antibody (Sueki et al, 2020). Based on proteomics of mass spectrometry has excellent analytical functions and is very suitable for basic research and clinical diagnosis of human diseases (Cifani and Kentsis, 2017). Metabolites control the expression of genes and proteins to a large extent, and drive key covalent chemical modi cations of DNA and RNA (such as methylation) and proteins (post-translational modi cation), thereby affecting cell function (Rinschen et al, 2019).…”