Instituto de Investigaciones Biotecnológicas "Dr. Raul Alfonsin", CONICET-Universidad Nacional de General San Martín, Chascomús, B7130IWA, Argentina.
CREG, CONICET-Universidad Nacional de La Plata, La Plata, CP 1900, Argentina.
Sci Rep. 2019 Jan 24;9(1):646. doi: 10.1038/s41598-018-36671-y.
Infectious diseases are of great relevance for global health, but needed drugs and vaccines have not been developed yet or are not effective in many cases. In fact, traditional scientific approaches with intense focus on individual genes or proteins have not been successful in providing new treatments. Hence, innovations in technology and computational methods provide new tools to further understand complex biological systems such as pathogen biology. In this paper, we apply a gene regulatory network approach to analyze transcriptomic data of the parasite Toxoplasma gondii. By means of an optimization procedure, the phenotypic transitions between the stages associated with the life cycle of T. gondii were embedded into the dynamics of a gene regulatory network. Thus, through this methodology we were able to reconstruct a gene regulatory network able to emulate the life cycle of the pathogen. The community network analysis has revealed that nodes of the network can be organized in seven communities which allow us to assign putative functions to 338 previously uncharacterized genes, 25 of which are predicted as new pathogenic factors. Furthermore, we identified a small gene circuit that drives a series of phenotypic transitions that characterize the life cycle of this pathogen. These new findings can contribute to the understanding of parasite pathogenesis.
传染病对全球健康具有重要意义，但目前仍未开发出所需的药物和疫苗，或者在许多情况下效果不佳。事实上，传统的科学方法过于关注单个基因或蛋白质，未能成功提供新的治疗方法。因此，技术和计算方法的创新为进一步理解复杂的生物系统（如病原体生物学）提供了新的工具。在本文中，我们应用基因调控网络方法来分析寄生虫刚地弓形虫的转录组数据。通过优化过程，与刚地弓形虫生命周期相关的阶段之间的表型转变被嵌入到基因调控网络的动态中。因此，通过这种方法，我们能够重建一个能够模拟病原体生命周期的基因调控网络。社区网络分析表明，网络节点可以组织成七个社区，这使我们能够为 338 个以前未表征的基因赋予推测的功能，其中 25 个被预测为新的致病因素。此外，我们确定了一个小的基因电路，该电路驱动一系列表型转变，这些转变特征化了这种病原体的生命周期。这些新发现有助于理解寄生虫发病机制。
