Chemometrics & Statistics
Novel tools for the analysis and integration of post-genomic datasets are required to maximise the benefit that can be derived from top-down systems biology approaches to understanding human health and disease.
Pattern Recognition and Expert Systems
Researchers in Biomolecular Medicine have been responsible for a number of the other recent developments in this field, including the development of expert systems for toxicity classicaition, application of genetic algorithms to optimise sample and variable selection, spectral alignment and calibration.
Statistical Spectroscopy
The development of statistical spectroscopy methods for information recovery from complex biofluid datasets has been driven forward in recent years and is now established as an efficient way of interrogating spectral data. Following the initial demonstration of statistical total correlation spectroscopy (STOCSY, Cloarec et al. (2005)) as a tool in metabonomics, an array of methods have been developed that combined various types of spectral data.
Multi-Omic Integration
Combining information from multiple omics platforms promises to allow a more holistic approach to understanding the complexity of mammalian biochemistry and Biomolecular Medicine continue to develop novel statistical and pathway-based approaches for data integration.
Curve Resolution
Recovering the latent information related to subtle time-modulated changes present in complex overlapped spectra is a considerable challenge. We have developed curve resolution methods based on the conept of spectrotype subunits of global profiles that enable such subtle features to be efficient revealed (Richards et al. (2008)).
Key Recent Publications
Garcia-Perez I, Couto Alves A, Angulo S, Li JV, Utzinger J, Ebbels TM, Legido-Quigley C, Nicholson JK, Holmes E, Barbas C. 2010. Bidirectional correlation of NMR and capillary electrophoresis fingerprints: a new approach to investigating Schistosoma mansoni infection in a mouse model. Anal Chem 82(1):203-10.
Ipsen A, Want EJ, Lindon JC, Ebbels TM. 2010. A statistically rigorous test for the identification of parent-fragment pairs in LC-MS datasets. Anal Chem 82(5):1766-78.
Veselkov KA, Lindon JC, Ebbels TMD, Crockford D, Volynkin VV, Holmes E, Davies DB, Nicholson JK. 2009. Recursive Segment-Wise Peak Alignment of Biological H-1 NMR Spectra for Improved Metabolic Biomarker Recovery. Analytical Chemistry 81(1):56-66.
Maher AD, Cloarec O, Patki P, Craggs M, Holmes E, Lindon JC, Nicholson JK. 2009. Dynamic biochemical information recovery in spontaneous human seminal fluid reactions via 1H NMR kinetic statistical total correlation spectroscopy. Anal Chem 81(1):288-95.
Sands CJ, Coen M, Maher AD, Ebbels TM, Holmes E, Lindon JC, Nicholson JK. 2009. Statistical total correlation spectroscopy editing of 1H NMR spectra of biofluids: application to drug metabolite profile identification and enhanced information recovery. Anal Chem 81(15):6458-66.
Alves AC, Rantalainen M, Holmes E, Nicholson JK, Ebbels TM. 2009. Analytic properties of statistical total correlation spectroscopy based information recovery in 1H NMR metabolic data sets. Anal Chem 81(6):2075-84.
Robinette SL, Veselkov KA, Bohus E, Coen M, Keun HC, Ebbels TM, Beckonert O, Holmes EC, Lindon JC, Nicholson JK. 2009. Cluster analysis statistical spectroscopy using nuclear magnetic resonance generated metabolic data sets from perturbed biological systems. Anal Chem 81(16):6581-9.
Pearce JT, Athersuch TJ, Ebbels TM, Lindon JC, Nicholson JK, Keun HC. 2008. Robust algorithms for automated chemical shift calibration of 1D 1H NMR spectra of blood serum. Anal Chem 80(18):7158-62.
Maher AD, Crockford D, Toft H, Malmodin D, Faber JH, McCarthy MI, Barrett A, Allen M, Walker M, Holmes E and others. 2008. Optimization of human plasma 1H NMR spectroscopic data processing for high-throughput metabolic phenotyping studies and detection of insulin resistance related to type 2 diabetes. Anal Chem 80(19):7354-62.
Richards SE, Wang Y, Lawler D, Kochhar S, Holmes E, Lindon JC, Nicholson JK. 2008. Self-modeling curve resolution recovery of temporal metabolite signal modulation in NMR spectroscopic data sets: application to a life-long caloric restriction study in dogs. Anal Chem 80(13):4876-85.
Richards S, Miller R, Gemperline P. 2008. Advantages of soft versus hard constraints in self-modeling curve resolution problems. Penalty alternating least squares (P-ALS) extension to multi-way problems. Appl Spectrosc 62(2):197-206.
Smith LM, Maher AD, Cloarec O, Rantalainen M, Tang H, Elliott P, Stamler J, Lindon JC, Holmes E, Nicholson JK. 2007. Statistical correlation and projection methods for improved information recovery from diffusion-edited NMR spectra of biological samples. Anal Chem 79(15):5682-9.
Cloarec O, Dumas ME, Craig A, Barton RH, Trygg J, Hudson J, Blancher C, Gauguier D, Lindon JC, Holmes E and others. 2005. Statistical total correlation spectroscopy: an exploratory approach for latent biomarker identification from metabolic 1H NMR data sets. Anal Chem 77(5):1282-9.
