Genetics, Vol. 166, 1037-1052, February 2004, Copyright © 2004

Identification of Genetic Networks

Momiao Xionga, Jun Lia, and Xiangzhong Fanga
a Human Genetics Center, University of Texas, Houston Health Science Center, Houston, Texas 77030

Corresponding author: Momiao Xiong, University of Texas, 1200 Herman Pressler, Houston, TX 77225., mxiong{at}sph.uth.tmc.edu (E-mail)

Communicating editor: J. B. WALSH

In this report, we propose the use of structural equations as a tool for identifying and modeling genetic networks and genetic algorithms for searching the most likely genetic networks that best fit the data. After genetic networks are identified, it is fundamental to identify those networks influencing cell phenotypes. To accomplish this task we extend the concept of differential expression of the genes, widely used in gene expression data analysis, to genetic networks. We propose a definition for the differential expression of a genetic network and use the generalized T2 statistic to measure the ability of genetic networks to distinguish different phenotypes. However, describing the differential expression of genetic networks is not enough for understanding biological systems because differences in the expression of genetic networks do not directly reflect regulatory strength between gene activities. Therefore, in this report we also introduce the concept of differentially regulated genetic networks, which has the potential to assess changes of gene regulation in response to perturbation in the environment and may provide new insights into the mechanism of diseases and biological processes. We propose five novel statistics to measure the differences in regulation of genetic networks. To illustrate the concepts and methods for reconstruction of genetic networks and identification of association of genetic networks with function, we applied the proposed models and algorithms to three data sets.





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