Quantifying robustness of the gap gene network

• Published in: Journal of theoretical biology 2024-03, Vol.580, p.111720-111720, Article 111720
• Main Authors: Andreas, Elizabeth, Cummins, Breschine, Gedeon, Tomáš
• Format: Article
• Language: English
• Subjects: Animals; Drosophila - genetics; Drosophila melanogaster - genetics; Embryo, Mammalian; Gene Regulatory Networks
• ISSN: 0022-5193; 1095-8541
• DOI: 10.1016/j.jtbi.2024.111720

Early development of Drosophila melanogaster (fruit fly) facilitated by the gap gene network has been shown to be incredibly robust, and the same patterns emerge even when the process is seriously disrupted. We investigate this robustness using a previously developed computational framework called DSGRN (Dynamic Signatures Generated by Regulatory Networks). Our mathematical innovations include the conceptual extension of this established modeling technique to enable modeling of spatially monotone environmental effects, as well as the development of a collection of graph theoretic robustness scores for network models. This allows us to rank order the robustness of network models of cellular systems where each cell contains the same genetic network topology but operates under a parameter regime that changes continuously from cell to cell. We demonstrate the power of this method by comparing the robustness of two previously introduced network models of gap gene expression along the anterior-posterior axis of the fruit fly embryo, both to each other and to a random sample of networks with same number of nodes and edges. We observe that there is a substantial difference in robustness scores between the two models. Our biological insight is that random network topologies are in general capable of reproducing complex patterns of expression, but that using measures of robustness to rank order networks permits a large reduction in hypothesis space for highly conserved systems such as developmental networks.