title: Approaching clinical proteomics: current state and future fields of application in cellular proteomics.
abstract: Recent developments in proteomics technology offer new opportunities for clinical applications in hospital or specialized laboratories including the identification of novel biomarkers, monitoring of disease, detecting adverse effects of drugs, and environmental hazards. Advanced spectrometry technologies and the development of new protein array formats have brought these analyses to a standard, which now has the potential to be used in clinical diagnostics. Besides standardization of methodologies and distribution of proteomic data into public databases, the nature of the human body fluid proteome with its high dynamic range in protein concentrations, its quantitation problems, and its extreme complexity present enormous challenges. Molecular cell biology (cytomics) with its link to proteomics is a new fast moving scientific field, which addresses functional cell analysis and bioinformatic approaches to search for novel cellular proteomic biomarkers or their release products into body fluids that provide better insight into the enormous biocomplexity of disease processes and are suitable for patient stratification, therapeutic monitoring, and prediction of prognosis. Experience from studies of in vitro diagnostics and especially in clinical chemistry showed that the majority of errors occurs in the preanalytical phase and the setup of the diagnostic strategy. This is also true for clinical proteomics where similar preanalytical variables such as inter- and intra-assay variability due to biological variations or proteolytical activities in the sample will most likely also influence the results of proteomics studies. However, before complex proteomic analysis can be introduced at a broader level into the clinic, standardization of the preanalytical phase including patient preparation, sample collection, sample preparation, sample storage, measurement, and data analysis is another issue which has to be improved. In this report, we discuss the recent advances and applications that fulfill the criteria for clinical proteomics with the focus on cellular proteomics (cytoproteomics) as related to preanalytical and analytical standardization and to quality control measures required for effective implementation of these technologies and analytes into routine laboratory testing to generate novel actionable health information. It will then be crucial to design and carry out clinical studies that can eventually identify novel clinical diagnostic strategies based on these techniques and validate their impact on clinical decision making.
authors.affiliation: European Bioinformatics Institute, Hinxton, United Kingdom.
authors.forename: Rolf
authors.initials: R
authors.lastname: Apweiler
authors.forename: Charalampos
authors.initials: C
authors.lastname: Aslanidis
authors.forename: Thomas
authors.initials: T
authors.lastname: Deufel
authors.forename: Andreas
authors.initials: A
authors.lastname: Gerstner
authors.forename: Jens
authors.initials: J
authors.lastname: Hansen
authors.forename: Dennis
authors.initials: D
authors.lastname: Hochstrasser
authors.forename: Roland
authors.initials: R
authors.lastname: Kellner
authors.forename: Markus
authors.initials: M
authors.lastname: Kubicek
authors.forename: Friedrich
authors.initials: F
authors.lastname: Lottspeich
authors.forename: Edmund
authors.initials: E
authors.lastname: Maser
authors.forename: Hans-Werner
authors.initials: HW
authors.lastname: Mewes
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.forename: Stefan
authors.initials: S
authors.lastname: Müllner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Mutter
authors.forename: Michael
authors.initials: M
authors.lastname: Neumaier
authors.forename: Peter
authors.initials: P
authors.lastname: Nollau
authors.forename: Hans G
authors.initials: HG
authors.lastname: Nothwang
authors.forename: Fredrik
authors.initials: F
authors.lastname: Ponten
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Knut
authors.initials: K
authors.lastname: Reinert
authors.forename: Gregor
authors.initials: G
authors.lastname: Rothe
authors.forename: Hannes
authors.initials: H
authors.lastname: Stockinger
authors.forename: Attila
authors.initials: A
authors.lastname: Tárnok
authors.forename: Mike J
authors.initials: MJ
authors.lastname: Taussig
authors.forename: Andreas
authors.initials: A
authors.lastname: Thiel
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.forename: Marius
authors.initials: M
authors.lastname: Ueffing
authors.forename: Günther
authors.initials: G
authors.lastname: Valet
authors.forename: Joel
authors.initials: J
authors.lastname: Vandekerckhove
authors.forename: Christoph
authors.initials: C
authors.lastname: Wagener
authors.forename: Oswald
authors.initials: O
authors.lastname: Wagner
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
mesh_terms: D053000:Analytic Sample Preparation Methods; D002477:Cells / Q000378:metabolism*; D019295:Computational Biology; D006801:Humans; D040901:Proteomics / Q000379:methods* / Q000592:standards / Q000639:trends*; D013223:Statistics as Topic