title: CSF biomarker discovery using label-free nano-LC-MS based proteomic profiling: technical aspects.
abstract: Biomarker discovery in cerebrospinal fluid (CSF) can provide important information helping to diagnose and monitor disease progression in brain disorders. We present a label-free LC-MS strategy to investigate the proteomic profile of CSF. We provide a framework and protocol addressing quality control, sample replication steps and the adaptation of pattern recognition methods for the detection of experimental variation and (most importantly) putative biomarkers. This strategy was tested using a total of 20 CSF samples (ten samples from healthy volunteers and ten from schizophrenia patients). A clear difference was found between healthy volunteers and schizophrenia patients. With technical and biological variation controlled, we were able to detect 77 proteins with confidence in CSF, of which seven were newly identified, without prior depletion of abundant protein species. Our strategy provides a simple and controlled method for CSF biomarker discovery.
authors: Institute of Biotechnology, University of Cambridge, Cambridge, UK.
authors: Jeffrey T J
authors: JT
authors: Huang
authors: Therese
authors: T
authors: McKenna
authors: Chris
authors: C
authors: Hughes
authors: F Markus
authors: FM
authors: Leweke
authors: Emanuel
authors: E
authors: Schwarz
authors: Sabine
authors: S
authors: Bahn
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis* / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D036103:Nanotechnology / Q000379:methods*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins; D010446:Peptide Fragments; D010751:Phosphopyruvate Hydratase