Onto-Tools, the toolkit of the modern biologist: Onto-Express, Onto-Compare, Onto-Design and Onto-Translate

Abstract

Onto-Tools is a set of four seamlessly integrated databases: Onto-Express, Onto-Compare, Onto-Design and Onto-Translate. Onto-Express is able to automatically translate lists of genes found to be differentially regulated in a given condition into functional profiles characterizing the impact of the condition studied upon various biological processes and pathways. OE constructs functional profiles (using Gene Ontology terms) for the following categories: biochemical function, biological process, cellular role, cellular component, molecular function and chromosome location. Statistical significance values are calculated for each category. Once the initial exploratory analysis identified a number of relevant biological processes, specific mechanisms of interactions can be hypothesized for the conditions studied. Currently, many commercial arrays are available for the investigation of specific mechanisms. Each such array is characterized by a biological bias determined by the extent to which the genes present on the array represent specific pathways. Onto-Compare is a tool that allows efficient comparisons of any sets of commercial or custom arrays. Using Onto-Compare, a researcher can determine quickly which array, or set of arrays, covers best the hypotheses studied. In many situations, no commercial arrays are available for specific biological mechanisms. Onto-Design is a tool that allows the user to select genes that represent given functional categories. Onto-Translate allows the user to translate easily lists of accession numbers, UniGene clusters and Affymetrix probes into one another. All tools above are seamlessly integrated. The Onto-Tools are available online at http://vortex.cs.wayne.edu/Projects.html.

Figure 1

Onto-Tools (clockwise, from top left): regulated genes are analyzed with Onto-Express to find significantly impacted biological processes. Specific hypotheses can be formulated based on such processes. Onto-Compare can be used to select those commercial microarrays that cover best the hypothesized mechanism. If no satisfactory array is available, Onto-Design can be used to design a custom array for that specific set of hypotheses. Onto-Translate may be used at any time to translate between UniGene cluster IDs, accession numbers and array specific Affymetrix identifiers.

Figure 2

Significant correlations were observed between the expression level and poor breast cancer outcome for 231 genes (7). This subset of genes was processed by Onto-Express to categorize the genes into functional groups. Red bar graphs represent genes for which the function was inferred, blue graphs represent genes for which the function was proved experimentally and green graphs represent genes for which this type of information was not recorded in the source database.