Approaching clinical proteomics: current state and future fields of application in fluid proteomics
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Rolf Apweiler
Abstract
The field of clinical proteomics offers opportunities to identify new disease biomarkers in body fluids, cells and tissues. These biomarkers can be used in clinical applications for diagnosis, stratification of patients for specific treatment, or therapy monitoring. New protein array formats and improved spectrometry technologies have brought these analyses to a level with potential for use in clinical diagnostics. The nature of the human body fluid proteome with its large dynamic range of protein concentrations presents problems with quantitation. The extreme complexity of the proteome in body fluids presents enormous challenges and requires the establishment of standard operating procedures for handling of specimens, increasing sensitivity for detection and bioinformatical tools for distribution of proteomic data into the public domain. From studies of in vitro diagnostics, especially in clinical chemistry, it is evident that most errors occur in the preanalytical phase and during implementation of the diagnostic strategy. This is also true for clinical proteomics, and especially for fluid proteomics because of the multiple pretreatment processes. These processes include depletion of high-abundance proteins from plasma or enrichment processes for urine where biological variation or differences in proteolytic activities in the sample along with preanalytical variables such as inter- and intra-assay variability will likely influence the results of proteomics studies. However, before proteomic analysis can be introduced at a broader level into the clinical setting, standardization of the preanalytical phase including patient preparation, sample collection, sample preparation, sample storage, measurement and data analysis needs to be improved. In this review, we discuss the recent technological advances and applications that fulfil the criteria for clinical proteomics, with the focus on fluid proteomics. These advances relate to preanalytical factors, analytical standardization and quality-control measures required for effective implementation into routine laboratory testing in order to generate clinically useful information. With new disease biomarker candidates, it will be crucial to design and perform clinical studies that can identify novel diagnostic strategies based on these techniques, and to validate their impact on clinical decision-making.
Clin Chem Lab Med 2009;47:724–44.
©2009 by Walter de Gruyter Berlin New York
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Artikel in diesem Heft
- Editorial
- A focus on recent advances in proteomics – one step closer to entrance into the clinical arena
- Reviews
- Proteomics in protein misfolding diseases
- Multidimensional protein identification technology for clinical proteomic analysis
- Technical advances in proteomics mass spectrometry: identification of post-translational modifications
- Mass spectrometry based proteomics profiling as diagnostic tool in oncology: current status and future perspective
- Research Papers
- Thrombin induces broad spectrum proteolysis in human serum samples
- Influence of sample storage duration on serum protein profiles assessed by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS)
- Proteomics of exhaled breath: methodological nuances and pitfalls
- Pancreatic cancer biomarkers discovery by surface-enhanced laser desorption and ionization time-of-flight mass spectrometry
- Approaching clinical proteomics: current state and future fields of application in fluid proteomics
- Genetics and Molecular Diagnostics
- Detection of Hpdel in healthy individuals and cancer patients in Taiwan
- Increased CA 19-9 level in patients without malignant disease
- General Clinical Chemistry and Laboratory Medicine
- Quantitation of cerebrospinal fluid lactic acid in infectious and non-infectious neurological diseases
- Proficiency testing project for brain natriuretic peptide (BNP) and the N-terminal part of the propeptide of BNP (NT-proBNP) immunoassays: the CardioOrmocheck study
- Reference Values and Biological Variations
- Influence of tourniquet application on venous blood sampling for serum chemistry, hematological parameters, leukocyte activation and erythrocyte mechanical properties
- Systemic cytokine response following exercise-induced muscle damage in humans
- Letters to the Editor
- CACNA1A gene non-synonymous single nucleotide polymorphisms and common migraine in Italy: a case-control association study with a micro-array technology
- Proficiency test of plasma free and total metanephrines: report from a study group
