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Improving the analysis of designed studies by combining statistical modelling with study design information

Author: Thissen, U. · Wopereis, S. · Berg, S.A.A. van den · Bobeldijk, I. · Kleemann, R. · Kooistra, T. · Dijk, K.W. van · Ommen, B. van · Smilde, A.K.
Institution: TNO Kwaliteit van Leven
Source:BMC Bioinformatics, 10
Identifier: 241414
doi: doi:10.1186/1471-2105-10-52
Article number: 52
Keywords: Biology · Biomedical Research · Animals · Databases, Factual · Humans · Metabolomics · Models, Statistical


Background: In the fields of life sciences, so-called designed studies are used for studying complex biological systems. The data derived from these studies comply with a study design aimed at generating relevant information while diminishing unwanted variation (noise). Knowledge about the study design can be used to decompose the total data into data blocks that are associated with specific effects. Subsequent statistical analysis can be improved by this decomposition if these are applied on selected combinations of effects. Results: The benefit of this approach was demonstrated with an analysis that combines multivariate PLS (Partial Least Squares) regression with data decomposition from ANOVA (Analysis of Variance): ANOVA-PLS. As a case, a nutritional intervention study is used on Apoliprotein E3-Leiden (APOE3Leiden) transgenic mice to study the relation between liver lipidomics and a plasma inflammation marker, Serum Amyloid A. The ANOVA-PLS performance was compared to PLS regression on the non-decomposed data with respect to the quality of the modelled relation, model reliability, and interpretability. Conclusion: It was shown that ANOVA-PLS leads to a better statistical model that is more reliable and better interpretable compared to standard PLS analysis. From a following biological interpretation, more relevant metabolites were derived from the model. The concept of combining data composition with a subsequent statistical analysis, as in ANOVA-PLS, is however not limited to PLS regression in metabolomics but can be applied for many statistical methods and many different types of data. © 2009 Thissen et al; licensee BioMed Central Ltd.