title: Gene set analysis exploiting the topology of a pathway.
abstract: BACKGROUND
  Recently, a great effort in microarray data analysis is directed towards the study of the so-called gene sets. A gene set is defined by genes that are, somehow, functionally related. For example, genes appearing in a known biological pathway naturally define a gene set. The gene sets are usually identified from a priori biological knowledge. Nowadays, many bioinformatics resources store such kind of knowledge (see, for example, the Kyoto Encyclopedia of Genes and Genomes, among others). Although pathways maps carry important information about the structure of correlation among genes that should not be neglected, the currently available multivariate methods for gene set analysis do not fully exploit it.
  
  
  RESULTS
  We propose a novel gene set analysis specifically designed for gene sets defined by pathways. Such analysis, based on graphical models, explicitly incorporates the dependence structure among genes highlighted by the topology of pathways. The analysis is designed to be used for overall surveillance of changes in a pathway in different experimental conditions. In fact, under different circumstances, not only the expression of the genes in a pathway, but also the strength of their relations may change. The methods resulting from the proposal allow both to test for variations in the strength of the links, and to properly account for heteroschedasticity in the usual tests for differential expression.
  
  
  CONCLUSIONS
  The use of graphical models allows a deeper look at the components of the pathway that can be tested separately and compared marginally. In this way it is possible to test single components of the pathway and highlight only those involved in its deregulation.
authors.affiliation: Department of Statistical Sciences, University of Padova, via C, Battisti 241, Padova, Italy.
authors.forename: Maria Sofia
authors.initials: MS
authors.lastname: Massa
authors.forename: Monica
authors.initials: M
authors.lastname: Chiogna
authors.forename: Chiara
authors.initials: C
authors.lastname: Romualdi
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods*; D003196:Computer Graphics; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D011947:Receptors, Antigen, B-Cell; D066246:ErbB Receptors
references.citation: Science. 2004 Aug 20;305(5687):1163-7
references.pmid: 15284455
references.citation: Bioinformatics. 2009 Apr 1;25(7):897-903
references.pmid: 19254923
references.citation: Clin Cancer Res. 2005 Oct 15;11(20):7209-19
references.pmid: 16243790
references.citation: Cell Cycle. 2008 Feb 1;7(3):297-303
references.pmid: 18235236
references.citation: Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11746-50
references.pmid: 8524841
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
references.pmid: 11309499
references.citation: BMC Bioinformatics. 2007 Nov 07;8:431
references.pmid: 17988400
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D619-22
references.pmid: 18981052
references.citation: Brief Bioinform. 2009 Jan;10(1):24-34
references.pmid: 18836208
references.citation: Brief Bioinform. 2008 May;9(3):189-97
references.pmid: 18202032
references.citation: J Clin Oncol. 2006 Apr 10;24(11):1679-88
references.pmid: 16549822
references.citation: PLoS Biol. 2008 Jul 22;6(7):e184
references.pmid: 18651794
references.citation: BMC Bioinformatics. 2009 Sep 22;10:306
references.pmid: 19772654
references.citation: Methods Inf Med. 2005;44(3):449-53
references.pmid: 16113772
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):8961-5
references.pmid: 15951424
references.citation: Nucleic Acids Res. 1999 Jan 1;27(1):29-34
references.pmid: 9847135
references.citation: BMC Bioinformatics. 2009 Feb 03;10:47
references.pmid: 19192285
references.citation: Leukemia. 2009 Sep;23(9):1622-7
references.pmid: 19357699
references.citation: Genes Dev. 1998 Apr 1;12(7):968-81
references.pmid: 9531535
references.citation: Bioinformatics. 2008 Feb 15;24(4):537-44
references.pmid: 18203773
references.citation: BMC Bioinformatics. 2007 Sep 27;8 Suppl 6:S5
references.pmid: 17903286
references.citation: Stat Appl Genet Mol Biol. 2005;4:Article32
references.pmid: 16646851