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Combined Top-Down and Bottom-Up Mass Spectrometric Approach to Characterization of Biomarkers for Renal Disease
journal contribution
posted on 2005-11-15, 00:00 authored by Michael J. Chalmers, Colin Logan Mackay, Christopher L. Hendrickson, Stefan Wittke, Michael Walden, Harald Mischak, Danilo Fliser, Ingo Just, Alan G. MarshallHere we describe a mass spectrometry (MS) approach for
biomarker discovery and structural characterization, based
on both top-down and bottom-up analyses. Capillary
electrophoresis (CE) coupled to electrospray ionization
(ESI) time-of-flight (TOF) MS serves to separate and mass-measure the thousands of polypeptides contained in
human urine. Statistical analysis of the differences between healthy control samples and patients with focal-segmental glomerulosclerosis, membranous glomerulonephritis, minimal change disease, IgA nephropathy, and
diabetic nephropathy validates multiple biomarkers for
the control and each of the diseases. To identify those
biomarkers, we employ preparative CE, enabling direct
infusion ESI MS analysis, followed by sample manipulation and reanalysis where necessary. We show how
tandem Fourier transform ion cyclotron resonance (FT-ICR) MS identifies these sometimes large (>8 kDa)
biomarkers. Critically, we maintain connectivity between
the CE TOF MS data and the ICR data used for biomarker
identification.
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electrospray ionizationcontrol samplesbiomarker identificationmass spectrometrybiomarker discoverychange diseaseCE TOF MS datainfusion ESI MS analysissample manipulationion cyclotron resonanceCapillary electrophoresisnephropathy validatesmembranous glomerulonephritisICR dataRenal Diseasetandem FourierStatistical analysisIgA nephropathy
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