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Colloquium - Racunas

CAD Tools for Biological Knowledge
Stephen Racunas
The Huck Institutes of Life Sciences, Pennsylvania State University

Advances in genomics and proteomics have led to a wealth of new experimental data, and biological databases and knowledge bases are proliferating rapidly. These developments offer biologists new opportunities to understand how organisms function, but also require new analysis techniques. Existing methods encounter problems fusing multiple data types, so we develop and present an event-based representation that helps overcome these difficulties while representing biological systems in a way that is compatible with notation used by experimental biologists.

We define and characterize the space of possible regulatory hypotheses that can be made about a particular biological system given an ontology for that system. We develop a biologically-motivated structure for this hypothesis space and show how to form classes of hypothesis variants generated from a starting hypothesis by, for instance, tweaking its parameters, borrowing analogous portions from other biological systems, or proposing extensions to the explanation offered by the initial hypothesis. We also introduce an event-based control theory specifically designed for biological systems, and introduce and characterize the notion of discoverability for regulatory events.

To demonstrate these concepts, we implemented a prototype hypothesis proofreading system and deployed this prototype for galactose metabolism in yeast. This software uses a contradiction-based approach that is more capable of handling large data sets than existing modeling approaches. As evidence of scalability, we expand our demonstration to include the set of all of the hypothesized metabolic reactions for humans, and show how to use the techniques we have developed to proofread the knowledge base containing the proposed "human reactome."

Department of Computer Science
University of Colorado Boulder
Boulder, CO 80309-0430 USA
May 5, 2012 (14:13)