Approaching clinical proteomics: current state and future fields of application in cellular proteomics.
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.
Apweiler
Rolf
R
European Bioinformatics Institute, Hinxton, United Kingdom.
Aslanidis
Charalampos
C
Deufel
Thomas
T
Gerstner
Andreas
A
Hansen
Jens
J
Hochstrasser
Dennis
D
Kellner
Roland
R
Kubicek
Markus
M
Lottspeich
Friedrich
F
Maser
Edmund
E
Mewes
Hans-Werner
HW
Meyer
Helmut E
HE
Müllner
Stefan
S
Mutter
Wolfgang
W
Neumaier
Michael
M
Nollau
Peter
P
Nothwang
Hans G
HG
Ponten
Fredrik
F
Radbruch
Andreas
A
Reinert
Knut
K
Rothe
Gregor
G
Stockinger
Hannes
H
Tárnok
Attila
A
Taussig
Mike J
MJ
Thiel
Andreas
A
Thiery
Joachim
J
Ueffing
Marius
M
Valet
Günther
G
Vandekerckhove
Joel
J
Wagener
Christoph
C
Wagner
Oswald
O
Schmitz
Gerd
G
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