efficient reverse-engineering of a developmental gene regulatory network高效的发育基因调控网络的逆向工程.pdfVIP

Efficient Reverse-Engineering of a Developmental Gene Regulatory Network 1. 1. 1 2 1 Anton Crombach , Karl R. Wotton , Damjan Cicin-Sain , Maksat Ashyraliyev , Johannes Jaeger * 1 EMBL/CRG Research Unit in Systems Biology, Centre for Genomic Regulation (CRG) and Universitat Pompeu Fabra (UPF), Barcelona, Spain, 2 Department of Mathematics and Computer Sciences, Bahc¸es¸ehir University, Istanbul, Turkey Abstract Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology. Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data. This approach is called reverse engineering. It has been successfully applied to many gene networks in various biological systems. However, to reconstitute the structure and non-linear dynamics of a developmental gene network in its spatial context remains a considerable challenge. Here, we address this challenge using a case study: the gap gene network involved in segment determination during early development of Drosophila melanogaster. A major problem for reverse-engineering pattern-forming networks is the significant amount of time and effort required to acquire and quantify spatial gene expression data. We have developed a simplified data processing pipeline that considerably increases the throughput of the method, but results in data of reduced accuracy compared to those previously used for gap gene network inference. We demonstrate that we can infer the correct network structure using our reduced data set, and investigate minimal data requirement