PT  - JOURNAL ARTICLE
AU  - Kumar, Tarun
AU  - Blondel, Leo
AU  - Extavour, Cassandra G.
TI  - Topology-driven analysis of protein-protein interaction networks detects functional genetic modules regulating reproductive capacity
AID  - 10.1101/852897
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 852897
4099  - http://biorxiv.org/content/early/2019/11/30/852897.short
4100  - http://biorxiv.org/content/early/2019/11/30/852897.full
AB  - Understanding the genetic regulation of organ structure is a fundamental problem in developmental biology. Here, we use egg-producing structures of insect ovaries, called ovarioles, to deduce systems-level gene regulatory relationships from quantitative functional genetic analysis. We previously showed that Hippo signalling, a conserved regulator of animal organ size, regulates ovariole number in Drosophila melanogaster. To comprehensively determine how Hippo signalling interacts with other pathways in this regulation, we screened all known signalling pathway genes, and identified Hpo-dependent and Hpo-independent signalling requirements. Network analysis of known protein-protein interactions among screen results identified independent gene regulatory modules regulating one or both of ovariole number and egg laying. These modules predict involvement of previously uncharacterised genes with higher accuracy than the original candidate screen. This shows that network analysis combining functional genetic and large-scale interaction data can predict function of novel genes regulating development.