03382nas a2200325 4500008004100000022001400041245007200055210006900127260001600196300000800212490000700220520234600227653001502573653002102588653004402609653002602653653002802679653001102707653003002718653001302748653001102761653004402772653003002816653003102846100002002877700001902897700002502916700002002941856009502961 2009 eng d a1471-216400aGene set internal coherence in the context of functional profiling.0 aGene set internal coherence in the context of functional profili c2009 Apr 27 a1970 v103 a
BACKGROUND: Functional profiling methods have been extensively used in the context of high-throughput experiments and, in particular, in microarray data analysis. Such methods use available biological information to define different types of functional gene modules (e.g. gene ontology -GO-, KEGG pathways, etc.) whose representation in a pre-defined list of genes is further studied. In the most popular type of microarray experimental designs (e.g. up- or down-regulated genes, clusters of co-expressing genes, etc.) or in other genomic experiments (e.g. Chip-on-chip, epigenomics, etc.) these lists are composed by genes with a high degree of co-expression. Therefore, an implicit assumption in the application of functional profiling methods within this context is that the genes corresponding to the modules tested are effectively defining sets of co-expressing genes. Nevertheless not all the functional modules are biologically coherent entities in terms of co-expression, which will eventually hinder its detection with conventional methods of functional enrichment.
RESULTS: Using a large collection of microarray data we have carried out a detailed survey of internal correlation in GO terms and KEGG pathways, providing a coherence index to be used for measuring functional module co-regulation. An unexpected low level of internal correlation was found among the modules studied. Only around 30% of the modules defined by GO terms and 57% of the modules defined by KEGG pathways display an internal correlation higher than the expected by chance.This information on the internal correlation of the genes within the functional modules can be used in the context of a logistic regression model in a simple way to improve their detection in gene expression experiments.
CONCLUSION: For the first time, an exhaustive study on the internal co-expression of the most popular functional categories has been carried out. Interestingly, the real level of coexpression within many of them is lower than expected (or even inexistent), which will preclude its detection by means of most conventional functional profiling methods. If the gene-to-function correlation information is used in functional profiling methods, the results obtained improve the ones obtained by conventional enrichment methods.
10aAlgorithms10aBreast Neoplasms10aCarcinoma, Intraductal, Noninfiltrating10aComputational Biology10aDatabases, Nucleic Acid10aFemale10aGene Expression Profiling10aGenomics10aHumans10aOligonucleotide Array Sequence Analysis10aPapillomavirus Infections10aReproducibility of Results1 aMontaner, David1 aMinguez, Pablo1 aAl-Shahrour, Fátima1 aDopazo, Joaquin uhttp://clinbioinfosspa.es/content/gene-set-internal-coherence-context-functional-profiling