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  • Gene set enrichment analysis of RNA-Seq data

    I was wondering if anyone is aware of a gene
    set enrichment algorithm for RNA-Seq data that:

    1) does not require a specification of differentially
    expressed (DE) genes (i.e.no need to use a hard
    p-value threshold cutoff for determining the DE gene
    list)

    2) uses subject sampling instead of gene sampling
    to obtain the p-value (i.e.this would maintain
    gene-gene correlations)

    Basically, I'm looking for a
    self-contained/subject sampling method (e.g.
    SAM-GS for microarray data) or a "hybrid" method
    (e.g. GSEA for microarray data). The only gene set
    enrichment algorithm that I am aware of for RNA-Seq
    data is GOSeq, but it uses a competitive/gene
    sampling method (i.e. Fisher's Exact Test).
    Note, the ideas of self-contained vs competitive and
    subject sampling vs gene sampling come from the
    following paper: Goeman JJ, Bühlmann P.Analyzing
    gene expression data in terms of gene sets:
    methodological issues. Bioinformatics. 2007 Apr 15;23(8)

    Something like GSEA-SNP is close to what I want.
    It uses a test-statistic that is suitable for discrete data
    and uses subject sampling to calculate the p-values.

    Thanks,
    Julie

  • #2
    Gsva

    Hi!
    You could try the GSVA package in Bioconductor:
    Gene Set Variation Analysis (GSVA) is a non-parametric, unsupervised method for estimating variation of gene set enrichment through the samples of a expression data set. GSVA performs a change in coordinate systems, transforming the data from a gene by sample matrix to a gene-set by sample matrix, thereby allowing the evaluation of pathway enrichment for each sample. This new matrix of GSVA enrichment scores facilitates applying standard analytical methods like functional enrichment, survival analysis, clustering, CNV-pathway analysis or cross-tissue pathway analysis, in a pathway-centric manner.


    In the vignette http://www.bioconductor.org/packages...t/doc/GSVA.pdf in section 6 they explain how to use it on RNA-seq data. You do not need any DE genes. For the detection of DE gene sets they use limma from which you will obtain a p-value. They do not seem to offer one.

    HTH
    Ninni

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