A novel method for generation of signature networks as biomarkers from complex high throughput data
Section snippets
Data annotation and software programming
An interactive, manually annotated database was derived from literature publications on proteins and small molecules (MetaCore™, GeneGo, St. Joseph, MI). This was developed with an Oracle version 9.2.0.4 Standard Edition (Oracle, Redwood Shores, CA) based architecture for the representation of biological functionality and integration of functional, molecular, or clinical information (Bugrim et al., 2004). Functional processes are the core objects in the database which can be of a different
Results
The original 2-D hierarchical clustering at 0.5, 2, 4, 12 and 24 h time points showed both compounds caused nearly identical expression patterns at early time points, featuring induction of cell cycle progression genes (Hodges et al., 2003) (Fig. 1A). Ultimately, E2 treatment leads to cell proliferation, while OHT treated cells largely remain arrested at G0. An additional supervised analysis (applicable when the distinct phenotypes are well defined (Quackenbush, 2001)) revealed E2 induced
Discussion
Traditionally, the functional organization of a biological system has been described in terms of pathways. Since Hartwell et al. (1999) hypothesized that many biological functions are carried out by discrete modules of physically interacting proteins (Hartwell et al., 1999), searching for interacting proteins and networks has become a key use for the functional analysis of microarrays. It is well documented that the outcome of microarray analysis is largely dependent upon statistical procedures
Acknowledgements
Dr. Craig Giroux (Wayne State University) and Dr. Christopher Bradfield (McCardle Cancer Institute) are acknowledged for their support and discussions. Our colleagues at GeneGo, Drs. Sergey Andreyev, Svetlana Sorokina, Tatyana Serebrijskaya, Roman Zuev, Andrej Ryabov, Eugene Kirillov, Eugene A. Rakhmatulin are sincerely acknowledged for their continuing contributions to software development and data annotation.
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