TY - JOUR T1 - Reverse Engineering the Gap Gene Network of Drosophila melanogaster A1 - Perkins, Theodore J A1 - Jaeger, Johannes A1 - Reinitz, John A1 - Glass, Leon Y1 - 2006/05/19 N2 - 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. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 2 IS - 5 UR - https://doi.org/10.1371/journal.pcbi.0020051 SP - e51 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.0020051 ER -