Journal ArticleDOI
Quantitative analysis of the intra- and inter-individual variability of the normal urinary proteome.
Nagarjuna Nagaraj,Matthias Mann +1 more
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TLDR
Determination of the normal fluctuation of individual urinary proteins should be useful in establishing significance thresholds in biomarker studies and allowed definition of a common and abundant set of 500 proteins that were readily detectable in all studied individuals.Abstract:
Urine is a readily and noninvasively obtainable body fluid. Mass spectrometry (MS)-based proteomics has shown that urine contains thousands of proteins. Urine is a potential source of biomarkers for diseases of proximal and distal tissues but it is thought to be more variable than the more commonly used plasma. By LC-MS/MS analysis on an LTQ-Orbitrap without prefractionation we characterized the urinary proteome of seven normal human donors over three consecutive days. Label-free quantification of triplicate single runs covered the urinary proteome to a depth of more than 600 proteins. The median coefficient of variation (cv) of technical replicates was 0.18. Interday variability was markedly higher with a cv of 0.48 and the overall variation of the urinary proteome between individuals was 0.66. Thus technical variability in our data was 7.5%, whereas intrapersonal variability contributed 45.5% and interpersonal variability contributed 47.1% to total variability. Determination of the normal fluctuation of individual urinary proteins should be useful in establishing significance thresholds in biomarker studies. Our data also allowed definition of a common and abundant set of 500 proteins that were readily detectable in all studied individuals. This core urinary proteome has a high proportion of secreted, membrane, and relatively high-molecular weight proteins.read more
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Journal ArticleDOI
Urine proteome of autosomal dominant polycystic kidney disease patients
Magda Bakun,Mariusz Niemczyk,Dominik Domanski,Radoslaw Jazwiec,Anna Perzanowska,Stanisław Niemczyk,Michał Kistowski,Agnieszka Fabijanska,Agnieszka Borowiec,Leszek Paczek,Michal Dadlez,Michal Dadlez +11 more
TL;DR: The aim of this study was to characterize the higher molecular weight fraction of urinary proteome of ADPKD population in comparison to healthy controls as a part of a general effort aiming at exhaustive characterization of human urine proteome in health and disease, preceding establishment of clinically useful disease marker panel.
Journal ArticleDOI
Urinary exosomal proteins as (pan-)cancer biomarkers: insights from the proteome.
TL;DR: MS‐based proteomic data on urinary exosomes from cancer patients is analysed, and the potential of urinaryExosome‐derived biomarkers in cancer is discussed.
Journal ArticleDOI
Dynamic changes of urinary proteins in a focal segmental glomerulosclerosis rat model
TL;DR: A rat model of adriamycin-induced nephropathy resembling human focal segmental glomerulosclerosis (FSGS) development is used to identify proteins changed in different stages of FSGS in rat models, which may aid in biomarker development and the understanding ofFSGS pathogenesis.
Journal ArticleDOI
Precise quantitation of 136 urinary proteins by LC/MRM-MS using stable isotope labeled peptides as internal standards for biomarker discovery and/or verification studies.
Andrew J. Percy,Juncong Yang,Darryl B. Hardie,Andrew G. Chambers,Jessica Tamura-Wells,Christoph H. Borchers +5 more
TL;DR: This work has systematically advanced and rigorously assessed the methodology toward the precise quantitation of the largest, multiplexed panel of candidate protein biomarkers in human urine to date, and the analysis strategy and discussion of the utility of this method in translational studies are discussed.
Journal ArticleDOI
High performance computational analysis of large-scale proteome data sets to assess incremental contribution to coverage of the human genome.
Nadin Neuhauser,Nagarjuna Nagaraj,Peter McHardy,Sara Zanivan,Richard A. Scheltema,Juergen Cox,Matthias Mann +6 more
TL;DR: This work describes parallelization and memory optimization of the MaxQuant software with the aim of executing it on a large computer cluster and finds that the most time-consuming algorithms are those detecting peptide features in the MS(1) data as well as the fragment spectrum search.
References
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Jiirgen Cox,Matthias Mann +1 more
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Journal ArticleDOI
Mass spectrometry-based proteomics
Ruedi Aebersold,Matthias Mann +1 more
TL;DR: The ability of mass spectrometry to identify and, increasingly, to precisely quantify thousands of proteins from complex samples can be expected to impact broadly on biology and medicine.
Journal ArticleDOI
Universal sample preparation method for proteome analysis
TL;DR: A method is described, filter-aided sample preparation (FASP), which combines the advantages of in-gel and in-solution digestion for mass spectrometry–based proteomics and allows single-run analyses of organelles and an unprecedented depth of proteome coverage.
Journal ArticleDOI
Stop and Go extraction tips for matrix-assisted laser desorption/ionization, nanoelectrospray, and lc/ms sample pretreatment in proteomics
TL;DR: A novel procedure in which a very small disk of beads embedded in a Teflon meshwork is placed as a microcolumn into pipet tips, finding that the Stage system is well-suited as a universal sample preparation system for proteomics.