基于基因组尺度集成细胞网络解析中华绒螯蟹蜕皮通路

Cellular network is a hot research topic in the field of systems biology, which can provide guidance and forecast for the biological experiment and synthetic biological path design. At present, the cellular networks are all established based on the microorganisms, but none of any advanced specie network has been reconstructed. In addition, the method of reconstructing the cellular network through multi network integration is still immature. For the purpose of reconstructing the first integrated cellular network of advanced specie and analyzing the molting pathway of Eriocheir sinensis, we firstly proposed the integration of genome-scale metabolic and protein-protein interaction networks to reconstruct the integrated cellular network of E. sinensis. Subsequently, according to the detection of differentially expressed genes among different stages of molting circle, the molting related core protein was determined with the integrated cellular network and validated by experiment. Finally, the molting route was iteratively predicted by the integrated cell network and validated by the protein-protein interaction experiment until finally obtain the entire pathway. This project will not only fill the blank of cellular network study on advanced species, but also first propose the method of realizing the function of multi-network integration with metabolite and protein-protein interaction dual network integration. On the other hand, the integrated-cellular-network-based analysis provides an innovative method for the research of molting mechanism in E. sinensis. The expected results of this project will promote the development of integrated cellular networks and the study of molting mechanism in aquatic crustaceans from molecular level.

细胞网络是系统生物学的研究热点，能够为生物实验和合成生物学路径设计提供指导和预测。目前细胞网络多基于微生物建立，对于高等生物尚未涉及；同时，通过多网络集成构建细胞网络的方法尚不成熟。本项目以构建第一个高等生物集成细胞网络，并利用该网络解析中华绒螯蟹蜕皮通路为目标，首先提出以基因组尺度代谢-蛋白互作网络集成的方法，构建中华绒螯蟹集成细胞网络；随后，结合蜕皮不同阶段的基因表达差异，通过集成细胞网络确定蜕皮相关的核心蛋白并进行实验验证；最后，利用集成细胞网络预测蜕皮通路，并结合蛋白互作实验进行通路修正，最终解析完整的蜕皮通路。本项目不仅填补了细胞网络研究在高等生物中的空白，同时首次以代谢-蛋白互作双网络集成实现多网络集成功能；另一方面，基于集成细胞网络解析蜕皮通路的方法为中华绒螯蟹蜕皮机制的研究提供了创新思路。本项目的预期研究成果将从分子水平上推动集成细胞网络的发展及水生甲壳动物蜕皮机制的研究。

细胞网络是系统生物学的研究热点，能够为生物实验和合成生物学路径设计提供指导和预测。目前细胞网络多基于微生物建立，对于高等生物尚未涉及；同时，通过多网络集成构建细胞网络的方法尚不成熟。本项目以构建第一个高等生物集成细胞网络，并利用该网络解析中华绒螯蟹蜕皮通路为目标，首先构建了中华绒螯蟹基因组尺度代谢网络和蛋白互作网络；随后开发了基因组尺度代谢-蛋白互作网络集成的方法，构建了中华绒螯蟹集成细胞网络；最后通过集成细胞网络确定蜕皮相关的核心蛋白并解析蜕皮通路。本项目已完成项目预期的集成网络构建方法的开发并构建了中华绒螯蟹代谢-蛋白互作集成网络，该网络是首个高等生物集成细胞网络。利用该网络确定了9个蜕皮相关的核心蛋白和两条蜕皮通路。本项目的研究成果从分子水平上推动了集成细胞网络的发展及水生甲壳动物蜕皮机制的研究。.本项目共发表论文9篇，其中SCI论文7篇，其中二区论文4篇，三区2篇，四区1篇；国际常设会议ICBBB2022论文1篇；核心期刊论文1篇。在ICBBB2022会议做分组报告。与加拿大卡尔加里大学合作发表SCI论文3篇。在细胞网络构建及分析方法方面申请专利4项。项目培养教授一名，副教授一名，已培养硕士研究生6人，其中2人获得国家奖学金资助和校级三好学生称号，5人获得学院一等奖学金资助。