New modes of data partitioning based on PARS peak alignment for improved multivariate biomarker/biopattern detection in1H-NMR spectroscopic metabolic profiling of urine.
This paper addresses the possibility of mathematically partition and process urine1H-NMR spectra to enhance the efficiency of the subsequent multivariate data analysis in the context of metabolic profiling of a toxicity study. We show that by processing the NMR data with the peak alignment using reduced set mapping (PARS) algorithm and the use of sparse representation of the data results in the information contained in the original NMR data being preserved with retained resolution but free of the problem of peak shifts. We can now describe a method for differential expression analysis of NMR spectra by using prior knowledge,i.e., the onset of dosing, a partitioning not possible to achieve using raw or bucketed data. In addition we also outline a scheme for soft removal of "biological noise" from the aligned data: exhaustive bio-noise subtraction (EBS). The result is a straightforward protocol for detection of peaks that appear as a consequence of the drug response. In other words, it is possible to elucidate peak origin, either from endogenous substancesorfrom the administered drug/biomarkers. The partition of data originating from the normally regulating metabolome can, furthermore, be analyzed free of the superimposed biological noise. The proposed protocol results in enhanced interpretability of the processed data,i.e., a more refined metabolic trace, simplification of detection of consistent biomarkers, and a simplified search for metabolic end products of the administered drug.
Department of Analytical Chemistry, BioSysteMetrics Group, Stockholm University, SE-106 91 Stockholm, Sweden ; Safety Assessment, Molecular Toxicology, AstraZeneca R&D Södertälje, SE-151 85 Södertälje, Sweden.
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RJ
Torgrip
Safety Assessment, Molecular Toxicology, AstraZeneca R&D Södertälje, SE-151 85 Södertälje, Sweden.
J
J
Lindberg
Statistical Science, AstraZeneca R&D Södertälje, SE-151 85 Södertälje, Sweden.
M
M
Linder
Department of Analytical Chemistry, BioSysteMetrics Group, Stockholm University, SE-106 91 Stockholm, Sweden.
B
B
Karlberg
Department of Analytical Chemistry, BioSysteMetrics Group, Stockholm University, SE-106 91 Stockholm, Sweden ; PAR&D, AstraZeneca R&D Södertälje, SE-151 85 Södertälje, Sweden.
S P
SP
Jacobsson
Safety Assessment, Molecular Toxicology, AstraZeneca R&D Södertälje, SE-151 85 Södertälje, Sweden.
J
J
Kolmert
Safety Assessment, Molecular Toxicology, AstraZeneca R&D Södertälje, SE-151 85 Södertälje, Sweden.
I
I
Gustafsson
Safety Assessment, Molecular Toxicology, AstraZeneca R&D Södertälje, SE-151 85 Södertälje, Sweden.
I
I
Schuppe-Koistinen
1H-NMR; biofluid; hepatic steatosis; metabolic profiling; multivariate; peak alignment; urine