reverse engineering the gap gene network of drosophila melanogaster逆向工程黑腹果蝇的基因网络的差距.pdfVIP

Reverse Engineering the Gap Gene Network of Drosophila melanogaster Theodore J. Perkins1*, Johannes Jaeger2,3¤, John Reinitz2,3, Leon Glass4 1 McGill Centre for Bioinformatics, McGill University, Montreal, Quebec, Canada, 2 Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York, United States of America, 3 Center for Developmental Genetics, Stony Brook University, Stony Brook, New York, United States of America, 4 Centre for Nonlinear Dynamics, Department of Physiology, McGill University, Montreal, Quebec, Canada A fundamental problem in functional genomics is to determine the structure and dynamics of genetic networks based on expression data. We describe a new strategy for solving this problem and apply it to recently published data on early Drosophila melanogaster development. Our method is orders of magnitude faster than current fitting methods and allows us to fit different types of rules for expressing regulatory relationships. Specifically, we use our approach to fit models using a smooth nonlinear formalism for modeling gene regulation (gene circuits) as well as models using logical rules based on activation and repression thresholds for transcription factors. Our technique also allows us to infer regulatory relationships de novo or to test network structures suggested by the literature. We fit a series of models to test several outstanding questions about gap gene regulation, including regulation of and by hunchback and the role of autoactivation. Based on our modeling results and validation against the experimental literature, we propose a revised network structure for the gap gene system. Interestingly, some relationships in standard textbook models of gap gene regulation appear to be unnecessary for or even inconsistent with the details of gap gene expression during wild-type development. Citation: Perkins TJ, Jaeger J, Reinitz J, Glass L (2006