小儿呼吸道合胞病毒肺炎的代谢组学数据解析方法的筛选和优化研究

项目名称： 小儿呼吸道合胞病毒肺炎的代谢组学数据解析方法的筛选和优化研究

项目编号： No.21675059

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 数理科学和化学

项目作者： 周燕平

作者单位： 华中师范大学

项目金额： 30万元

中文摘要： 小儿呼吸道合胞病毒肺炎(Respiratory Syncytial Virus Pneumonia, RSVP)严重威胁小儿身体健康，目前对该病既无理想的治疗方法和药物，又无安全有效的疫苗。基于代谢组学在疾病筛查中的优势，本项目拟采用液相色谱-质谱联用技术表征小儿RSVP疾病组和小儿健康组的血浆中小分子代谢物水平；引入并完善机器学习领域中的集成算法，以传统非线性建模算法（如分类树、高斯过程、最小二乘-支持向量机和径向基函数网络等）为基础，探索发展高性能的适合于代谢组学数据特性的生物化学计量学方法来进行数据解析，以获得组间代谢差异，筛选潜在的生物标志物；进而构建其代谢网络，从而为RSVP的发病机制研究提供理论基础，为RSVP的预防、早期诊断、临床合理治疗和预后等提供理论指导。同时，通过本项目的开展，拟建立高通量代谢组学数据解析的信息学理论和方法，为后基因时代功能基因研究提供有效而实用的工具。

中文关键词： 呼吸道合胞病毒肺炎；代谢组学；化学计量学；集成

英文摘要： Respiratory syncytial virus (RSV) is one of the most important pathogenic infections of childhood and has significant morbidity and mortality. There are not yet desired therapeutic medicines and a convincing and safe vaccine available. In view of the advantages of metabolomics in disease diagnosis, the current project aims to combine UPLC/LTQ/Orbitrap-MS with some new developed multivariate chemometrics algorithms for recognizing the metabolic difference between the kids with respiratory syncytial virus-infected pneumonia and the healthy ones, identifying some biomarkers related to RSVP followed by constructing their metabolic network. UPLC/LTQ/Orbitrap-MS will be applied to detect the levels of small molecules in the plasma samples from two groups. The new multivariate algorithms for analyzing the obtained metabolomic profiles will be formed by combining the ensemble techniques and some traditional nonlinear modeling algorithms, i.e., classification tree (CT), Gaussian process (GP), radial basis function network (RBFN), least-squares support vector machine (LS-SVM). The execution of the current project may benefit for laying the foundation for mechanic research of RSVP and offering instructions for the prevention, early diagnosis, clinical rational treatment, and prognosis of RSVP. Moreover, the current project will establish the basic information theory and methodology for high-throughput analysis of data in metabolomics, and provide practical and effective tools for functional gene studies in post gene period.

英文关键词： respiratory syncytial virus pneumonia;metabolomics;chemometrics;ensemble