By a News Reporter-Staff News Editor at Life Science Weekly -- Investigators discuss new findings in Proteomics. According to news originating from St. Louis, Missouri, by NewsRx correspondents, research stated, "Biomarkers are required for pre-symptomatic diagnosis, treatment, and monitoring of neurodegenerative diseases such as Alzheimer's disease. Cerebrospinal fluid (CSF) is a favored source because its proteome reflects the composition of the brain."
Our news journalists obtained a quote from the research from the Washington University School of Medicine, "Ideal biomarkers have low technical and inter-individual variability (subject variance) among control subjects to minimize overlaps between clinical groups. This study evaluates a process of multi-affinity fractionation (MAF) and quantitative label-free liquid chromatography tandem mass spectrometry (LC-MS/MS) for CSF biomarker discovery by (1) identifying reparable sources of technical variability, (2) assessing subject variance and residual technical variability for numerous CSF proteins, and (3) testing its ability to segregate samples on the basis of desired biomarker characteristics. Fourteen aliquots of pooled CSF and two aliquots from six cognitively normal individuals were randomized, enriched for low-abundance proteins by MAF, digested endoproteolytically, randomized again, and analyzed by nano-LC-MS. Nano-LC-MS data were time and m/z aligned across samples for relative peptide quantification. Among 11,433 aligned charge groups, 1360 relatively abundant ones were annotated by MS2, yielding 823 unique peptides. Analyses, including Pearson correlations of annotated LC-MS ion chromatograms, performed for all pairwise sample comparisons, identified several sources of technical variability: i) incomplete MAF and keratins; ii) globally-or segmentally-decreased ion current in isolated LC-MS analyses; and iii) oxidized methionine-containing peptides. Exclusion of these sources yielded 609 peptides representing 81 proteins. Most of these proteins showed very low coefficients of variation (CV
According to the news editors, the research concluded: "Thus, this technique shows potential for biomarker discovery for neurological diseases."
For more information on this research see: Quantitative label-free proteomics for discovery of biomarkers in cerebrospinal fluid: assessment of technical and inter-individual variation. Plos One, 2013;8(5):e64314. (Public Library of Science - www.plos.org; Plos One - www.plosone.org)
The news correspondents report that additional information may be obtained from R.J. Perrin, Division of Neuropathology, Washington University School of Medicine, St Louis, Missouri, United States. Additional authors for this research include J.E. Payton, J.P. Malone, P. Gilmore, A.E. Davis, C. Xiong, A.M. Fagan, R.R. Townsend and D.M Holtzman (see also Proteomics).
Keywords for this news article include: Missouri, Peptides, Proteins, St. Louis, Proteomics, Amino Acids, United States, North and Central America.
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