GFINDer: Genome Function INtegrated Discoverer through dynamic annotation, statistical analysis, and mining

Abstract

Statistical and clustering analyses of gene expression results from high-density microarray experiments produce lists of hundreds of genes regulated differentially, or with particular expression profiles, in the conditions under study. Independent of the microarray platforms and analysis methods used, these lists must be biologically interpreted to gain a better knowledge of the patho-physiological phenomena involved. To this end, numerous biological annotations are available within heterogeneous and widely distributed databases. Although several tools have been developed for annotating lists of genes, most of them do not give methods for evaluating the relevance of the annotations provided, or for estimating the functional bias introduced by the gene set on the array used to identify the gene list considered. We developed Genome Functional INtegrated Discoverer (GFINDer), a web server able to automatically provide large-scale lists of user-classified genes with functional profiles biologically characterizing the different gene classes in the list. GFINDer automatically retrieves annotations of several functional categories from different sources, identifies the categories enriched in each class of a user-classified gene list and calculates statistical significance values for each category. Moreover, GFINDer enables the functional classification of genes according to mined functional categories and the statistical analysis is of the classifications obtained, aiding better interpretation of microarray experiment results. GFINDer is available online at http://www.medinfopoli.polimi.it/GFINDer/.

Figure 1

The three-layer GFINDer system architecture.

Figure 2

The gene list window.

Figure 3

Statistical analysis of the GO biological process categories represented in the RA-repressed genes considered. Red and blue P-values, and corresponding vertical lines on histogram bars, indicate the 1% and 5% significance levels, respectively.

Figure 4

Hierarchical Gene Ontology tree of the most statistically significant biological process category (i.e. cell cycle checkpoint) identified for the RA-repressed genes considered. As clearly appears, this is a child and a more specific category of the cell proliferation category.