Abstract
The utility of mass spectrometry (MS)-based proteomic analyses and their clinical applications have been increasingly recognized over the past decade due to their high sensitivity, specificity and throughput. MS-based proteomic measurements have been used in a wide range of biological and biomedical investigations, including analysis of cellular responses and disease-specific post-translational modifications. These studies greatly enhance our understanding of the complex and dynamic nature of the proteome in biology and disease. Some MS techniques, such as those for targeted analysis, are being successfully applied for biomarker verification, whereas others, including global quantitative analysis (for example, for biomarker discovery), are more challenging and require further development. However, recent technological improvements in sample processing, instrumental platforms, data acquisition approaches and informatics capabilities continue to advance MS-based applications. Improving the detection of significant changes in proteins through these advances shows great promise for the discovery of improved biomarker candidates that can be verified pre-clinically using targeted measurements, and ultimately used in clinical studies - for example, for early disease diagnosis or as targets for drug development and therapeutic intervention. Here, we review the current state of MS-based proteomics with regard to its advantages and current limitations, and we highlight its translational applications in studies of protein biomarkers.
Highlights
The utility of mass spectrometry (MS)-based proteomic analyses and their clinical applications have been increasingly recognized over the past decade due to their high sensitivity, speci city and throughput
Translational proteomics: the importance of mass spectrometry-based approaches Interest in using mass spectrometry (MS) for clinical analyses has grown significantly in the past few years due to its success in studies of human specimens, such as its recent applications for single cell analysis of bone marrow [1], direct blood sampling in multiple disease states, such as cardiac injury [2] and breast cancer [3], and the identification of Gram-negative bacilli in multiple clinical samples, including blood, tissue and urine [4,5]
Since human proteins perform cellular functions essential to health and/or disease, obtaining knowledge of their presence and variance is of great importance in understanding disease states and for advancing translational studies, especially those related to personalized medicine [9,10]
Summary
Depletion [33,34,35], fractionation [36], or a combination of all three with MS analyses. E detection of more proteins (for example, thousands) from plasma is possible with extensive off-line fractionation prior to on-line LC-MS analyses [38], but days or weeks of LC-MS measurements are necessary for analysis of the multiple fractions While this approach is highly attractive for the detection and discovery of potential biomarkers, the inherently low throughput largely precludes population studies to enable investigation of human and disease heterogeneity, and limits the possibility of performing personal profiling. Data-dependent MS/MS analysis of selected peptides relies on an initial MS scan, and it is widely used in proteomic discovery studies, it has inherent limitations that are associated with MS/MS under sampling in complex samples To overcome these limita tions and improve quantification, the accurate mass and time (AMT) tag strategy was developed for use on either labeled or label-free samples [52]. In a typical AMT tag study, a database is created and populated with peptide masses and LC elution times from many LC-MS/MS
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