用计算方法构建全基因组关联复杂疾病基因调控网络

Human health and life are influenced by complex diseases. And the pathogenesis is complex. It’s the key part of complex diseases prevention and therapy that the study on genome-wide association study (GWAS) gene regulatory network (GRN) construction and analysis. It has become an important focus research in bioinformatics. The aim of the project is to reconstruct GWAS GRNs of complex diseases and analyze the topology of networks using computational methods. For the limitation of the current research on complex diseases GRNs, a novel SNP clustering algorithm will be proposed to provide accurate data for complex disease GWAS GRNs construction. A novel mathematical model for GRNs will be proposed to adapt to the dynamic characteristics of complex disease GRNs. A novel optimization strategy of construction will be proposed to improve the algorithm accuracy for complex disease GRNs. The complex disease pathogenesis will be analyzed to develop a software for complex disease GWAS GRNs construction. The aim of the project is to achieve construction and analysis of complex disease GRNs, and to promote the research of bioinformatics. All of these have important theoretical significance and application value to explore the pathogenesis of complex diseases and drug design.

复杂疾病严重影响人类健康和生活，其致病机理复杂，从全基因组关联的基因调控网络构建与分析层面研究复杂疾病遗传特性和致病诱因是复杂疾病防治结合的关键所在，这已成为生物信息学的重要研究课题。本项目拟实现用计算方法构建面向全基因组关联研究的复杂疾病基因调控网络并分析网络的拓扑结构。针对当前复杂疾病基因调控网络研究的局限，拟提出全新的SNP聚类算法,为面向全基因组关联的复杂疾病基因调控网络构建提供精准数据；拟提出基因调控网络的新数学模型，以适应复杂疾病基因调控网络动态变化特性；拟提出新优化策略，提高复杂疾病基因调控网络构建精度时间比；深入研究和理解复杂疾病的发病机理，研发全基因组关联的复杂疾病基因调控网络构建与分析软件。本项目的研究以期实现复杂疾病基因调控网络构建与分析，推动生物信息学的研究发展，对于探究复杂疾病的发病机理和药物设计等具有重要的理论意义和应用价值。

针对目前人类复杂疾病（HCD）基因调控网络（GRN）构建与分析研究基因网络范围小，全局观不足的局限，开展了全基因组关联研究基因调控网络（GWASGRN）构建与分析，为复杂疾病开展全局观GRN动态变化研究；提出了新优化策略和新数学模型，基于阈值分析法和混合遗传算法的方式进行基因调控网络构建；分析了外界因素对未发病正常GRN稳定网络影响变化以及外界因素影响后GRN发生变化到发病的动态GWASGRN网络变化趋势。在GWASGRN结构框架下深入理解HCD的发病机理，找出了引起HCD相关GWASGRN发生动态变化并发病的诱因，研发了复杂疾病GWASGRN构建与分析的相关算法，为HCD的致病理论研究提供理论指导。