磷酸化相关的蛋白质翻译后修饰Crosstalk及激酶的计算识别方法和分析研究

项目名称： 磷酸化相关的蛋白质翻译后修饰Crosstalk及激酶的计算识别方法和分析研究

项目编号： No.61471331

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 无线电电子学、电信技术

项目作者： 王明会

作者单位： 中国科学技术大学

项目金额： 80万元

中文摘要： 蛋白质翻译后修饰（PTM）crosstalk是近年来发现的一种重要蛋白质功能调控机制，与多种重大疾病密切相关，其识别研究对全新PTM crosstalk的发现及相关分子机制的阐明意义重大，但目前国内外尚无有效的计算识别方法。本项目以备受关注的磷酸化相关PTM crosstalk为研究对象，引入信息融合的理念，提出计算识别的新思路。拟通过系统全面的生物信息学分析，明确不同类型PTM crosstalk在序列、共进化、底物功能等多方面的特性，采用信息融合的理论和方法，研究并发展基于多源异类生物信息融合的计算识别方法。此外，针对PTM crosstalk中多激酶协同修饰调控的识别难题，以激酶-底物催化关系相似性为突破点，发展基于相似性的激酶识别方法，探讨潜在的多激酶协同调控机制。本项目将为相关计算识别研究提供新的思路和方法，并为探索未知PTM crosstalk及潜在激酶调控机制提供科学依据。

中文关键词： 生物信息学；生物信息处理；机器学习；磷酸化；PTM；crosstalk

英文摘要： Recently, post-translational modification (PTM) crosstalk has been shown as an important regulatory mechanism of protein function, which is also implicated in serious diseases such as cancer. Identification of PTM crosstalk is of great significance to the discovery of novel PTM crosstalk and the elucidation of the underlying molecular mechanisms. However, currently there are no efficient computational methods for this purpose. This project aims to bring novel ideas for computational identification of well-studied phosphorylation related PTM crosstalks, by introducing the concept of information fusion. Specifically, we plan to elucidate the characteristics of protein sequence, co-evolution and substrate function between different PTM crosstalks based on systematic bioinformatics analysis, and adopt the theory and methodology of information fusion to design computational methods based on multi-source heterogeneous biological information. Furthermore, to tackle the issue introduced by co-regulation of PTM crosstalk by multiple protein kinases, we plan to develop kinase identification methods based on similarity between kinase-substrate catalytic relationships, and by this way explore potential collaborative multi-kinase regulatory mechanisms. This project will provide new ideas and methods for related computational identification research, and provide scientific evidence for unknown PTM crosstalk and potential kinase regulatory mechanisms.

英文关键词： Bioinformatics;Biological information processing;Machine learning;Phosphorylation;PTM crosstalk