title: Statistical search space reduction and two-dimensional data display approaches for UPLC-MS in biomarker discovery and pathway analysis.
abstract: 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.
authors.affiliation: Biological Chemistry, Division of Biomedical Sciences, Sir Alexander Fleming Building, Imperial College, London, SW7 2AZ, UK. d.crockford@imperial.ac.uk
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Crockford
authors.forename: John C
authors.initials: JC
authors.lastname: Lindon
authors.forename: Olivier
authors.initials: O
authors.lastname: Cloarec
authors.forename: Robert S
authors.initials: RS
authors.lastname: Plumb
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Bruce
authors.forename: Severine
authors.initials: S
authors.lastname: Zirah
authors.forename: Paul
authors.initials: P
authors.lastname: Rainville
authors.forename: Chris L
authors.initials: CL
authors.lastname: Stumpf
authors.forename: Kelly
authors.initials: K
authors.lastname: Johnson
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D002853:Chromatography, Liquid / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D051381:Rats
chemical_list: D015415:Biomarkers