整合多维度组学数据构建心力衰竭中核编码线粒体基因功能网络及分析

心力衰竭（心衰）是最重要的心血管疾病之一，大量研究表明线粒体功能异常与心衰的发生发展密切相关。98%的线粒体蛋白由核基因编码，系统研究心衰进程中核编码线粒体基因的表达模式，有助于深入揭示心衰的分子机制。申请者前期研究发现，在多种病因所致的心衰中，核编码线粒体基因的表达有显著变化。基于此，本项目拟通过整合多组学数据构建心衰中核编码线粒体基因功能网络，挖掘心衰进程中关键的核编码线粒体基因和子网络。首先通过整合多种病因所致心衰的转录组数据，系统地研究核编码线粒体基因的表达模式。其次通过概率模型整合不同类型的互作数据，构建心衰核编码线粒体基因功能网络。并采用机器学习算法对功能网络进行筛选，鉴定出在心衰发生发展中发挥重要作用的关键子网络及网络之间的调控关系。最后选取部分候选基因进行实验验证。本项目的实施有助于系统地认识核编码线粒体基因在心衰发生发展中的作用机制，进而为心衰的防治提供新的研究视角参考。

Heart failure (HF) is one of the most important cardiovascular diseases, and a large number of studies have shown that mitochondrial abnormalities are tightly associated with the development and progression of HF. About 98% of mitochondrial proteins are encoded by nuclear genes, a systematic study on the expression pattern of nuclear-encoded mitochondrial genes in the process of HF is helpful to understand the molecular mechanism of HF. The author's previous research has found that the expression of nuclear-encoded mitochondrial genes were significant changed under HFs caused by various etiologies. Based on this, this project intends to construct a nuclear-encoded mitochondrial gene function network under HF by integrating multiple omics data sets, and dig out the key genes and sub-networks in the process of HF. Firstly, we will systematically explore the expression pattern of nuclear-encoded mitochondrial genes in HF by integrating transcriptome data of HF from different etiologies. Then a human nuclear-encoded mitochondrial gene functional network will be constructed by integrating different types of interaction data through a probabilistic model. The machine learning algorithm will be used to screen the functional networks and identify the key sub-networks and genes that playing an important role in the development and progression of HF. Finally, we are going to select key nuclear-encoded mitochondrial genes in HF for further experimental verification. The implementation of this project will contribute to the systematic understanding of the molecular mechanism of nuclear-encoded mitochondrial genes in the development and progression of HF, and provide a new research perspective for the prevention and treatment of HF.