413 State Hall, Department of Computer Science, Wayne State University, Detroit MI 48202 Phone: (313) 577-5070 Fax: (313) 577-6868
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Articles reviewing our research !!
The typical result of a microarray experiment is a list of tens or hundreds of genes found to be differentially regulated in the condition under study. Independently of the methods used to select these genes, the common task faced by any researcher is to translate these lists of genes into a better understanding of the biological phenomena involved. Currently, this is done through a tedious combination of searches through the literature and a number of public databases. We developed Onto-Express (OE) as a novel tool able to automatically translate such lists of differentially regulated genes into functional profiles characterizing the impact of the condition studied. 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. We demonstrated the validity and the utility of this comprehensive global analysis of gene function by analyzing two breast cancer data sets from two separate laboratories. OE was able to identify correctly all biological processes postulated by the original authors, as well as discover novel relevant mechanisms (Draghici et.al, Genomics, 81(2), 2003). Other results obtained with Onto-Express can be found in Ostermeier et.al, Lancet, 360(9335), 2002.
Microarrays are at the center of a revolution in biotechnology, allowing researchers to screen tens of thousands of genes simultaneously. Typically, they have been used in exploratory research to help formulate hypotheses. In most cases, this phase is followed by a more focused, hypothesis driven stage in which certain specific biological processes and pathways are thought to be involved. Since a single biological process can still involve hundreds of genes, microarrays are still the preferred approach as proven by the availability of focused arrays from several manufacturers. Since focused arrays from different manufacturers use different sets of genes, each array will represent any given regulatory pathway to a different extent. We argue that a functional analysis of the arrays available should be the most important criterion used in the array selection. We developed Onto-Compare as a database that can provide this functionality, based on the GO nomenclature.
Many Laboratories chose to design and print their own microarrays. At present, the choice of the genes to include on a certain microarray is a very laborious process requiring a high level of expertise. Onto-Design database is able to assist the designers of custom microarrays by providing the means to select genes based on their biological process, molecular function or cellular component.
In the annotation world a same piece of information can be stored and viewed differently across different databases. For instance, more than one Affymetrix probe ids can refer to the same GenBank sequence (accession number) and more than one nucleotide sequence from GenBank can be grouped in a single UniGene cluster. The result of Onto-Express depends on whether the input list contains Affymetrix probe IDs, GenBank accession numbers or UniGene cluster IDs. The user has to be aware of relations between the different forms of the data in order to interpret correctly the results. Even if the user is aware of the relationships and knows how to convert them, most existing tools allow conversions of individual genes. Onto-Translate is a tool that allows the user to perform easily such translations.
Onto-Miner (OM) provide a single and convenient interface that allow the user to interrogate our databases regarding annotations of known genes. OM will return all known information about a given list of genes. Advantages or OM include the fact it allows queries with multiple genes and allows for scripting. This is unlike GenBank which uses a single gene navigation process.
The automated functional profiling approach of OE helps the researchers to better understand the biological phenomenon under study by pointing out statistically significant cellular functions. However, graphical representations of gene interactions (pathways) can be very useful. As more data becomes available, the question “is there a known pathway containing my gene(s) of interest?” will gradually transform into “how do I find the most interesting pathway(s) involving my gene(s)?”
Pathway-Express (PE) is a new tool in the Onto-Tools ensemble that is designed to answer such questions. Our goal is to provide a system that will automatically find such interesting pathways. When the user submits a list of genes, the system performs a search and builds a list of all associated pathways.
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