title: Piecewise multivariate modelling of sequential metabolic profiling data.
abstract: BACKGROUND
  Modelling the time-related behaviour of biological systems is essential for understanding their dynamic responses to perturbations. In metabolic profiling studies, the sampling rate and number of sampling points are often restricted due to experimental and biological constraints.
  
  
  RESULTS
  A supervised multivariate modelling approach with the objective to model the time-related variation in the data for short and sparsely sampled time-series is described. A set of piecewise Orthogonal Projections to Latent Structures (OPLS) models are estimated, describing changes between successive time points. The individual OPLS models are linear, but the piecewise combination of several models accommodates modelling and prediction of changes which are non-linear with respect to the time course. We demonstrate the method on both simulated and metabolic profiling data, illustrating how time related changes are successfully modelled and predicted.
  
  
  CONCLUSIONS
  The proposed method is effective for modelling and prediction of short and multivariate time series data. A key advantage of the method is model transparency, allowing easy interpretation of time-related variation in the data. The method provides a competitive complement to commonly applied multivariate methods such as OPLS and Principal Component Analysis (PCA) for modelling and analysis of short time-series data.
authors.affiliation: Research Group for Chemometrics, Institute of Chemistry, Umeå University, Umeå, S-901 87, Sweden. mattias.rantalainen@imperial.ac.uk
authors.forename: Mattias
authors.initials: M
authors.lastname: Rantalainen
authors.forename: Olivier
authors.initials: O
authors.lastname: Cloarec
authors.forename: Timothy M D
authors.initials: TM
authors.lastname: Ebbels
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Lundstedt
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.forename: Johan
authors.initials: J
authors.lastname: Trygg
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000503:physiopathology; D007700:Kinetics; D008627:Mercuric Chloride / Q000633:toxicity; D008660:Metabolism; D008954:Models, Biological; D015233:Models, Statistical; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D051381:Rats; D012016:Reference Values; D049490:Systems Biology / Q000379:methods / Q000706:statistics & numerical data; D013997:Time Factors
chemical_list: D008627:Mercuric Chloride