Epistasis Blog

From the Artificial Intelligence Innovation Lab at Cedars-Sinai Medical Center (www.epistasis.org)

Saturday, May 14, 2005

Epistasis and drug discovery

The Dartmouth CGL is pleased to note that our paper on "Combinatorial pharmacogenetics" has been accepted for publication in Nature Reviews Drug Discovery. It will appear this summer. The application of our multifactor dimensionality reduction (MDR) approach to pharmacogenetics is reviewed.

Wilke R, Reif D, Moore JH. Combinatorial pharmacogenetics. Nature Reviews Drug Discovery, in press (2005).


Combinatorial pharmacogenetics seeks to characterize genetic variations affecting reactions to potentially toxic agents within the complex metabolic networks of the human body. Polymorphic drug metabolizing enzymes (DME) are likely to represent some of the most common inheritable risk factors associated with common “disease” phenotypes, such as adverse drug reactions. The relatively high concordance between DME polymorphisms and clinical phenotypes suggests that research into this class of polymorphisms may benefit patients in the near-future. Characterization of other genes impacting drug disposition (absorption, distribution, metabolism, and elimination) will further enhance this process. As with most questions concerning biological systems, the complexity arises out of the combinatorial magnitude of all the possible interactions and pathways. The high-dimensionality of the resulting analysis problem will often overwhelm traditional analysis methods. Novel analysis techniques, such as multifactor dimensionality reduction (MDR), offer viable options for evaluating such data.


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