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.
Crockford
Derek J
DJ
Biological Chemistry, Division of Biomedical Sciences, Sir Alexander Fleming Building, Imperial College, London, SW7 2AZ, UK. d.crockford@imperial.ac.uk
Lindon
John C
JC
Cloarec
Olivier
O
Plumb
Robert S
RS
Bruce
Stephen J
SJ
Zirah
Severine
S
Rainville
Paul
P
Stumpf
Chris L
CL
Johnson
Kelly
K
Holmes
Elaine
E
Nicholson
Jeremy K
JK
D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D002853:Chromatography, Liquid / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D051381:Rats
D015415:Biomarkers