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Using Effective Subnetworks to Predict Selected Properties of Gene Networks 1 2,3 1 ¨ ¨ 4 Gemunu H. Gunaratne *, Preethi H. Gunaratne , Lars Seemann , Andrei Torok 1 Department of Physics, University of Houston, Houston, Texas, United States of America, 2 Department of Biology and Biochemistry, University of Houston, Houston, Texas, United States of America, 3 Human Genome Sequencing Center and Department of Pathology, Baylor College of Medicine, Houston, Texas, United States of America, 4 Department of Mathematics, University of Houston, Houston, Texas, United States of America Abstract Background: Difficulties associated with implementing gene therapy are caused by the complexity of the underlying regulatory networks. The forms of interactions between the hundreds of genes, proteins, and metabolites in these networks are not known very accurately. An alternative approach is to limit consideration to genes on the network. Steady state measurements of these influence networks can be obtained from DNA microarray experiments. However, since they contain a large number of nodes, the computation of influence networks requires a prohibitively large set of microarray experiments. Furthermore, error estimates of the network make verifiable predictions impossible. Methodology/Principal Findings: Here, we propose an alternative approach. Rather than attempting to derive an accurate model of the network, we ask what questions can be addressed using lower dimensional, highly simplified models. More importantly, is it possible to use such robust features in applications? We first identify a small group of genes that can be used to affect changes in other nodes