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Discovery and validation of protein biomarkers
10 July 2012 • Author(s): Péter Horvatovich & Rainer Bischoff, Analytical Biochemistry, Department of Pharmacy, University of Groningen
Biomarkers are biological characteristics that are objectively measured and evaluated as indicators of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention1. Biomarkers can be used to determine disease onset, progression, efficacy of drug treatment, patient susceptibility to develop a certain type of disease or predict efficacy of treatment at a particular disease stage2. Protein molecular biomarkers are particularly popular due to the availability of a large range of analytical instrumentation, which can identify and quantify proteins in complex biological samples.
Proteins are key compounds in biosynthesis, cell, tissue and organ signalling and provide cell and tissue structural stability in living organisms. The primary protein sequences are encoded in the genome; however, their complex posttranslational modifications (PTMs) and three dimensional structures are fairly unpredictable from genomic information. In this mini-review, we will provide an overview of the current state, challenge and important aspects of protein biomarker discovery and validation.
Biomarker research should start with defining the target normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention, what the biomarker should highlight. This is followed by setting up a team with medical, analytical and bioinformatics partners (Figure 1).
The medical partner is responsible for sample collection, storage and pre-classification of samples based on accurate clinical data (disease phenotype), and store samples and clinical information in biobanks. The analytical participant is responsible for the development of an analytical platform both for the discovery stage comprehensively measuring a low number of samples and for validation. Validation includes the targeted analysis of a preselected list of biomarker candidates in a large sample cohort. The bioinformatics partner is responsible for management, processing and accurate evaluation of all data acquired during the study. All of the three parties need to collaborate closely, and the work requires careful planning before starting the sample collection and analytical work3.
ABB Analytical Measurement ACD/Labs ADInstruments Ltd Advanced Analytical Technologies GmbH Analytik Jena AG Astell Scientific Ltd B&W Tek Bachem AG Bibby Scientific Limited Bio-Rad Laboratories BioNavis Ltd Biopharma Group Black Swan Analysis Limited Charles Ischi AG | Kraemer Elektronik Cherwell Laboratories CI Precision Cobalt Light Systems Coulter Partners CPC Biotech srl Dassault Systèmes BIOVIA DiscoverX Edinburgh Instruments Enterprise System Partners (ESP) EUROGENTEC F.P.S. Food and Pharma Systems Srl IDBS JEOL Europe L.B. Bohle Maschinen + Verfahren GmbH Lab M Ltd. LabWare Linkam Scientific Instruments Limited Molins Technologies Multicore Dynamics Ltd Nanosurf New England Biolabs, Inc. Panasonic Biomedical Sales Europe B.V. PerkinElmer Inc ReAgent Russell Finex Limited Source BioScience Takara Clontech Tornado Spectral Systems Tuttnauer Watson-Marlow Fluid Technology Group Wickham Laboratories Limited Xylem Analytics YMC Europe GmbH Yusen Logistics