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      Multilevel data analysis of a crossover designed human nutritional intervention study.

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          Abstract

          A new method is introduced for the analysis of 'omics' data derived from crossover designed drug or nutritional intervention studies. The method aims at finding systematic variations in metabolic profiles after a drug or nutritional challenge and takes advantage of the crossover design in the data. The method, which can be considered as a multivariate extension of a paired t test, generates different multivariate submodels for the between- and the within-subject variation in the data. A major advantage of this variation splitting is that each submodel can be analyzed separately without being confounded with the other variation sources. The power of the multilevel approach is demonstrated in a human nutritional intervention study which used NMR-based metabolomics to assess the metabolic impact of grape/wine extract consumption. The variations in the urine metabolic profiles are studied between and within the human subjects using the multilevel analysis. After variation splitting, multilevel PCA is used to investigate the experimental and biological differences between the subjects, whereas a multilevel PLS-DA model is used to reveal the net treatment effect within the subjects. The observed treatment effect is validated with cross model validation and permutations. It is shown that the statistical significance of the multilevel classification model ( p << 0.0002) is a major improvement compared to a ordinary PLS-DA model ( p = 0.058) without variation splitting. Finally, rank products are used to determine which NMR signals are most important in the multilevel classification model.

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          Author and article information

          Journal
          J Proteome Res
          Journal of proteome research
          American Chemical Society (ACS)
          1535-3893
          1535-3893
          Oct 2008
          : 7
          : 10
          Affiliations
          [1 ] Biosystems Data Analysis, Swammerdam Institute for Life Sciences, Universiteit van Amsterdam, Nieuwe Achtergracht 166, 1018 WV Amsterdam, The Netherlands.
          Article
          10.1021/pr800145j
          18754629
          f5336f43-3646-4695-9edf-d63b294b610d
          History

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