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    A novel approach for biomarker selection and the integration of repeated measures experiments from two assays

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    69
    Author
    Liquet, B; Le Cao, K-A; Hocini, H; Thiebaut, R
    Date
    2012-12-06
    Source Title
    BMC Bioinformatics
    Publisher
    BMC
    University of Melbourne Author/s
    Le Cao, Kim-Anh
    Affiliation
    School of Mathematics and Statistics
    Metadata
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    Document Type
    Journal Article
    Citations
    Liquet, B., Le Cao, K. -A., Hocini, H. & Thiebaut, R. (2012). A novel approach for biomarker selection and the integration of repeated measures experiments from two assays. BMC BIOINFORMATICS, 13 (1), https://doi.org/10.1186/1471-2105-13-325.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/259607
    DOI
    10.1186/1471-2105-13-325
    Abstract
    BACKGROUND: High throughput 'omics' experiments are usually designed to compare changes observed between different conditions (or interventions) and to identify biomarkers capable of characterizing each condition. We consider the complex structure of repeated measurements from different assays where different conditions are applied on the same subjects. RESULTS: We propose a two-step analysis combining a multilevel approach and a multivariate approach to reveal separately the effects of conditions within subjects from the biological variation between subjects. The approach is extended to two-factor designs and to the integration of two matched data sets. It allows internal variable selection to highlight genes able to discriminate the net condition effect within subjects. A simulation study was performed to demonstrate the good performance of the multilevel multivariate approach compared to a classical multivariate method. The multilevel multivariate approach outperformed the classical multivariate approach with respect to the classification error rate and the selection of relevant genes. The approach was applied to an HIV-vaccine trial evaluating the response with gene expression and cytokine secretion. The discriminant multilevel analysis selected a relevant subset of genes while the integrative multilevel analysis highlighted clusters of genes and cytokines that were highly correlated across the samples. CONCLUSIONS: Our combined multilevel multivariate approach may help in finding signatures of vaccine effect and allows for a better understanding of immunological mechanisms activated by the intervention. The integrative analysis revealed clusters of genes, that were associated with cytokine secretion. These clusters can be seen as gene signatures to predict future cytokine response. The approach is implemented in the R package mixOmics (http://cran.r-project.org/) with associated tutorials to perform the analysis(a).

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