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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Schlattmann, Peter / Tate, Jillian R. / Tsongalis, Gregory J.

12 Issues per year

IMPACT FACTOR 2013: 2.955
Rank 5 out of 29 in category Medical Laboratory Technology in the 2013 Thomson Reuters Journal Citation Report/Science Edition

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Approaching clinical proteomics: current state and future fields of application in fluid proteomics

Rolf Apweiler1, b / Charalampos Aslanidis2 / Thomas Deufel3, a / Andreas Gerstner4, c / Jens Hansen2 / Dennis Hochstrasser5, d / Roland Kellner6, b / Markus Kubicek7, e / Friedrich Lottspeich8, b / Edmund Maser9 / Hans-Werner Mewes10 / Helmut E. Meyer11, b / Stefan Müllner12, b, f / Wolfgang Mutter13, b / Michael Neumaier14, a / Peter Nollau15, a / Hans G. Nothwang16, a / Fredrik Ponten17 / Andreas Radbruch18, c / Knut Reinert19 / Gregor Rothe20, a / Hannes Stockinger21, c, f / Attila Tarnok22 / Mike J. Taussig23 / Andreas Thiel18, c / Joachim Thiery24, a / Marius Ueffing25, b / Günther Valet8, c / Joel Vandekerckhove26 / Wiltrud Verhuven27 / Christoph Wagener15, a / Oswald Wagner7, e, f / Gerd Schmitz2, a, b, f

1European Bioinformatics Institute, Welcome Trust Genome Campus, Hinxton, UK

2Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany

3Institute for Clinical Chemistry and Laboratory Diagnostics, University of Jena, Jena, Germany

4Department of Otorhinolaryngology/Surgery, University of Bonn, Bonn, Germany

5Department of Pathology/Clinical Chemistry, University of Geneva, Geneva, Switzerland

6Merck, Darmstadt, Germany

7Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Vienna, Austria

8Max-Planck-Institute for Biochemistry, Martinsried/Munich, Germany

9Institute of Toxicology and Pharmacology, University Kiel, Kiel, Germany

10Institute for Bioinformatics, GSF, Neuherberg, Germany

11Medical Proteomics Center, University of Bochum, Bochum, Germany

12Protagen, Dortmund, Germany

13PROFOS, Regensburg, Germany

14Institute for Clinical Chemistry, University Hospital Mannheim, Mannheim, Germany

15Institute for Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

16Department of Animal Physiology, Technical University Kaiserslautern, Kaiserslautern, Germany

17Institute for Genetics and Pathology, University of Uppsala, Uppsala, Sweden

18German Rheumatism Research Center Berlin, Berlin, Germany

19Department of Mathematics and Computer Science, University of Berlin, Berlin, Germany

20Laboratory Center Bremen, Bremen, Germany

21Department of Molecular Immunology, University of Vienna, Vienna, Austria

22Department of Pediatric Cardiology, University of Leipzig, Leipzig, Germany

23Technology Research Group, The Babraham Institute Cambridge, Cambridge, UK

24Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany

25Institute of Human Genetics, GSF Neuherberg, Neuherberg, Germany

26Department of Medical Protein Research, University of Gent, Gent, Belgium

27Waters, Eschborn, Germany

aConsensus document of the DGKL – Deutsche Vereinte Gesellschaft für Klinische Chemie und Laboratorioumsmedizin (www.dgkl.de)

bDGPF – Deutsche Gesellschaft für Proteomforschung (www.dgpf.org)

cDGfZ – Deutsche Gesellschaft für Zytometrie (www.dgfz.org)

dSSCC – Schweizerische Gesellschaft für Klinische Chemie (www.sscc.ch)

eÖGLMKC – Österreichische Gesellschaft für Laboratoriumsmedizin und Klinische Chemie (www.oeglmkc.at)

fDanubian Biobank Consortium (www.danubianbiobank.de)

Corresponding author: Prof. Dr. med. Gerd Schmitz, Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauß Allee 11, 93053 Regensburg, Germany Phone: +49-941-944-6201, Fax: +49-941-944-6202,

Citation Information: Clinical Chemistry and Laboratory Medicine. Volume 47, Issue 6, Pages 724–744, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2009.167, June 2009

Publication History



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.

Keywords: cerebrospinal fluid (CSF); clinical proteomics; fluid proteomics; mass spectrometry (MS); matrix assisted laser desorption/ionization (MALDI); preanalytical effects; standard operating procedures (SOP); surface-enhanced laser desorption/ionization (SELDI)

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