1H NMR and UPLC-MS(E) statistical heterospectroscopy: characterization of drug metabolites (xenometabolome) in epidemiological studies.

Statistical HeterospectroscopY (SHY) is a statistical strategy for the coanalysis of multiple spectroscopic data sets acquired in parallel on the same samples. This method operates through the analysis of the intrinsic covariance between signal intensities in the same and related molecular fingerprints measured by multiple spectroscopic techniques across cohorts of samples. Here, the method is applied to 600-MHz (1)H NMR and UPLC-TOF-MS (E) data obtained from human urine samples ( n = 86) from a subset of an epidemiological population unselected for any relevant phenotype or disease factor.

Integrative top-down system metabolic modeling in experimental disease states via data-driven Bayesian methods.

Multivariate metabolic profiles from biofluids such as urine and plasma are highly indicative of the biological fitness of complex organisms and can be captured analytically in order to derive top-down systems biology models. The application of currently available modeling approaches to human and animal metabolic pathway modeling is problematic because of multicompartmental cellular and tissue exchange of metabolites operating on many time scales. Hence, novel approaches are needed to analyze metabolic data obtained using minimally invasive sampling methods in order to reconstruct the patho-physiological modulations of metabolic interactions that are representative of whole system dynamics.

Statistical search space reduction and two-dimensional data display approaches for UPLC-MS in biomarker discovery and pathway analysis.

A new analytical strategy for biomarker recovery from directly coupled ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC Tof MS) data on biofluids is presented and exemplified using a study on hydrazine-induced liver toxicity. A key step in the strategy involves a novel procedure for reducing the spectroscopic search space by differential analysis of cohorts of normal and pathological samples using an orthogonal projection to latent structures discriminant analysis (O-PLS-DA). This efficiently sorts principal discriminators of toxicity from the background of thousands of metabolic features commonly observed in data sets generated by UPLC-MS analysis of biological fluids and is thus a powerful tool for biomarker discovery.

Statistical heterospectroscopy, an approach to the integrated analysis of NMR and UPLC-MS data sets: application in metabonomic toxicology studies.

Statistical heterospectroscopy (SHY) is a new statistical paradigm for the coanalysis of multispectroscopic data sets acquired on multiple samples. This method operates through the analysis of the intrinsic covariance between signal intensities in the same and related molecules measured by different techniques across cohorts of samples. The potential of SHY is illustrated using both 600-MHz 1H NMR and UPLC-TOFMS data obtained from control rat urine samples (n = 54) and from a corresponding hydrazine-treated group (n = 58).