PMID- 20811074 OWN - NLM STAT- MEDLINE DCOM- 20110103 LR - 20211020 IS - 1535-9484 (Electronic) IS - 1535-9476 (Print) IS - 1535-9476 (Linking) VI - 9 IP - 9 DP - 2010 Sep TI - Quantitative proteomics and metabolomics analysis of normal human cerebrospinal fluid samples. PG - 2063-75 LID - 10.1074/mcp.M900877-MCP200 [doi] AB - The analysis of cerebrospinal fluid (CSF) is used in biomarker discovery studies for various neurodegenerative central nervous system (CNS) disorders. However, little is known about variation of CSF proteins and metabolites between patients without neurological disorders. A baseline for a large number of CSF compounds appears to be lacking. To analyze the variation in CSF protein and metabolite abundances in a number of well-defined individual samples of patients undergoing routine, non-neurological surgical procedures, we determined the variation of various proteins and metabolites by multiple analytical platforms. A total of 126 common proteins were assessed for biological variations between individuals by ESI-Orbitrap. A large spread in inter-individual variation was observed (relative standard deviations [RSDs] ranged from 18 to 148%) for proteins with both high abundance and low abundance. Technical variation was between 15 and 30% for all 126 proteins. Metabolomics analysis was performed by means of GC-MS and nuclear magnetic resonance (NMR) imaging and amino acids were specifically analyzed by LC-MS/MS, resulting in the detection of more than 100 metabolites. The variation in the metabolome appears to be much more limited compared with the proteome: the observed RSDs ranged from 12 to 70%. Technical variation was less than 20% for almost all metabolites. Consequently, an understanding of the biological variation of proteins and metabolites in CSF of neurologically normal individuals appears to be essential for reliable interpretation of biomarker discovery studies for CNS disorders because such results may be influenced by natural inter-individual variations. Therefore, proteins and metabolites with high variation between individuals ought to be assessed with caution as candidate biomarkers because at least part of the difference observed between the diseased individuals and the controls will not be caused by the disease, but rather by the natural biological variation between individuals. FAU - Stoop, Marcel P AU - Stoop MP AD - Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands. FAU - Coulier, Leon AU - Coulier L FAU - Rosenling, Therese AU - Rosenling T FAU - Shi, Shanna AU - Shi S FAU - Smolinska, Agnieszka M AU - Smolinska AM FAU - Buydens, Lutgarde AU - Buydens L FAU - Ampt, Kirsten AU - Ampt K FAU - Stingl, Christoph AU - Stingl C FAU - Dane, Adrie AU - Dane A FAU - Muilwijk, Bas AU - Muilwijk B FAU - Luitwieler, Ronald L AU - Luitwieler RL FAU - Sillevis Smitt, Peter A E AU - Sillevis Smitt PA FAU - Hintzen, Rogier Q AU - Hintzen RQ FAU - Bischoff, Rainer AU - Bischoff R FAU - Wijmenga, Sybren S AU - Wijmenga SS FAU - Hankemeier, Thomas AU - Hankemeier T FAU - van Gool, Alain J AU - van Gool AJ FAU - Luider, Theo M AU - Luider TM LA - eng PT - Journal Article PL - United States TA - Mol Cell Proteomics JT - Molecular & cellular proteomics : MCP JID - 101125647 SB - IM MH - Case-Control Studies MH - Cerebrospinal Fluid/*metabolism MH - Chromatography, Liquid MH - Humans MH - Magnetic Resonance Spectroscopy MH - *Metabolomics MH - *Proteomics MH - Reproducibility of Results MH - Spectrometry, Mass, Electrospray Ionization MH - Tandem Mass Spectrometry PMC - PMC2938111 EDAT- 2010/09/03 06:00 MHDA- 2011/01/05 06:00 PMCR- 2011/09/01 CRDT- 2010/09/03 06:00 PHST- 2010/09/03 06:00 [entrez] PHST- 2010/09/03 06:00 [pubmed] PHST- 2011/01/05 06:00 [medline] PHST- 2011/09/01 00:00 [pmc-release] AID - S1535-9476(20)30916-6 [pii] AID - M110.000877 [pii] AID - 10.1074/mcp.M900877-MCP200 [doi] PST - ppublish SO - Mol Cell Proteomics. 2010 Sep;9(9):2063-75. doi: 10.1074/mcp.M900877-MCP200.