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MOTIVATION This paper presents a global test to be used for the analysis of microarray data. Using this test it can be determined whether the global expression pattern of a group of genes is significantly related to some clinical outcome of interest. Groups of genes may be any size from a single gene to all genes on the chip (e.g. known pathways, specific(More)
MOTIVATION Many statistical tests have been proposed in recent years for analyzing gene expression data in terms of gene sets, usually from Gene Ontology. These methods are based on widely different methodological assumptions. Some approaches test differential expression of each gene set against differential expression of the rest of the genes, whereas(More)
This article presents a novel algorithm that efficiently computes L(1) penalized (lasso) estimates of parameters in high-dimensional models. The lasso has the property that it simultaneously performs variable selection and shrinkage, which makes it very useful for finding interpretable prediction rules in high-dimensional data. The new algorithm is based on(More)
MOTIVATION A recent surge of interest in survival as the primary clinical endpoint of microarray studies has called for an extension of the Global Test methodology to survival. RESULTS We present a score test for association of the expression profile of one or more groups of genes with a (possibly censored) survival time. Groups of genes may be pathways,(More)
  • Susanne Osanto, Yongjun Qin, Henk P. Buermans, Johannes Berkers, Evelyne Lerut, Jelle J. Goeman +1 other
  • 2012
MicroRNAs (miRNAs), non-coding RNAs regulating gene expression, are frequently aberrantly expressed in human cancers. Next-generation deep sequencing technology enables genome-wide expression profiling of known miRNAs and discovery of novel miRNAs at unprecedented quantitative and qualitative accuracy. Deep sequencing was performed on 11 fresh frozen clear(More)
The choice for a polyadenylation site determines the length of the 3'-untranslated region (3'-UTRs) of an mRNA. Inclusion or exclusion of regulatory sequences in the 3'-UTR may ultimately affect gene expression levels. Poly(A) binding protein nuclear 1 (PABPN1) is involved in polyadenylation of pre-mRNAs. An alanine repeat expansion in PABPN1 (exp-PABPN1)(More)
MOTIVATION Current methods for multiplicity adjustment do not make use of the graph structure of Gene Ontology (GO) when testing for association of expression profiles of GO terms with a response variable. RESULTS We propose a multiple testing method, called the focus level procedure, that preserves the graph structure of Gene Ontology (GO). The procedure(More)
In genome-wide association studies (GWAS) of complex traits, single SNP analysis is still the most applied approach. However, the identified SNPs have small effects and provide limited biological insight. A more appropriate approach to interpret GWAS data of complex traits is to analyze the combined effect of a SNP set grouped per pathway or gene region. We(More)
DNA methylation has been recognized as a key mechanism in cell differentiation. Various studies have compared tissues to characterize epigenetically regulated genomic regions, but due to differences in study design and focus there still is no consensus as to the annotation of genomic regions predominantly involved in tissue-specific methylation. We used a(More)