title: Recursive segment-wise peak alignment of biological (1)h NMR spectra for improved metabolic biomarker recovery.
abstract: Chemical shift variation in small-molecule (1)H NMR signals of biofluids complicates biomarker information recovery in metabonomic studies when using multivariate statistical and pattern recognition tools. Current peak realignment methods are generally time-consuming or align major peaks at the expense of minor peak shift accuracy. We present a novel recursive segment-wise peak alignment (RSPA) method to reduce variability in peak positions across the multiple (1)H NMR spectra used in metabonomic studies. The method refines a segmentation of reference and test spectra in a top-down fashion, sequentially subdividing the initial larger segments, as required, to improve the local spectral alignment. We also describe a general procedure that allows robust comparison of realignment quality of various available methods for a range of peak intensities. The RSPA method is illustrated with respect to 140 (1)H NMR rat urine spectra from a caloric restriction study and is compared with several other widely used peak alignment methods. We demonstrate the superior performance of the RSPA alignment over a wide range of peaks and its capacity to enhance interpretability and robustness of multivariate statistical tools. The approach is widely applicable for NMR-based metabolic studies and is potentially suitable for many other types of data sets such as chromatographic profiles and MS data.
authors.affiliation: Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anesthetics (SORA), Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, London, UK.
authors.forename: Kirill A
authors.initials: KA
authors.lastname: Veselkov
authors.forename: John C
authors.initials: JC
authors.lastname: Lindon
authors.forename: Timothy M D
authors.initials: TM
authors.lastname: Ebbels
authors.forename: Derek
authors.initials: D
authors.lastname: Crockford
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Volynkin
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.forename: David B
authors.initials: DB
authors.lastname: Davies
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis* / Q000737:chemistry / Q000652:urine; D031204:Caloric Restriction; D008297:Male; D055432:Metabolomics / Q000379:methods*; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016482:Urinalysis / Q000379:methods
chemical_list: D015415:Biomarkers