title: Interdependence of signal processing and analysis of urine 1H NMR spectra for metabolic profiling.
abstract: Metabolic profiling of urine presents challenges because of the extensive random variation of metabolite concentrations and the dilution resulting from changes in the overall urine volume. Thus statistical analysis methods play a particularly important role; however, appropriate choices of these methods are not straightforward. Here we investigate constant and variance-stabilization normalization of raw and peak picked spectra, for use with exploratory analysis (principal component analysis) and confirmatory analysis (ordinary and Empirical Bayes t-test) in (1)H NMR-based metabolic profiling of urine. We compare the performance of these methods using urine samples spiked with known metabolites according to a Latin square design. We find that analysis of peak picked and logarithm-transformed spectra is preferred, and that signal processing and statistical analysis steps are interdependent. While variance-stabilizing transformation is preferred in conjunction with principal component analysis, constant normalization is more appropriate for use with a t-test. Empirical Bayes t-test provides more reliable conclusions when the number of samples in each group is relatively small. Performance of these methods is illustrated using a clinical metabolomics experiment on patients with type 1 diabetes to evaluate the effect of insulin deprivation.
authors: Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA.
authors: Shucha
authors: S
authors: Zhang
authors: Cheng
authors: C
authors: Zheng
authors: Ian R
authors: IR
authors: Lanza
authors: K Sreekumaran
authors: KS
authors: Nair
authors: Daniel
authors: D
authors: Raftery
authors: Olga
authors: O
authors: Vitek
mesh_terms: D002097:C-Reactive Protein / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D025341:Principal Component Analysis; D012815:Signal Processing, Computer-Assisted; D016482:Urinalysis
chemical_list: D002097:C-Reactive Protein