题目：Computational analysis of the phosphoproteomic data

时间：2015.9.25  星期五  上午10:00 – 11:30

地点：F东101会议室

邀请人：叶志强

嘉宾简介：
 
   薛宇，1980年6月出生，安徽合肥人，98年考入中国科学技术大学高分子科学与工程系，获高分子学士学位及计算机科学双学位，02年“硕博连读”于中国科大生命学院，06年获细胞生物学博士学位。07年至09年担任中国科大副教授，09年至今任华中科技大学生命科学与技术学院教授。主要研究方向为蛋白质翻译后修饰的生物信息学，近年来紧密围绕修饰底物和位点预测、修饰组学数据分析与功能修饰推断，以及翻译后修饰数据资源与可视化等重要科学与技术问题，采用由点及面、层层推进的研究策略，取得了阶段性研究成果。已发表SCI论文50多篇，引用1500多次。2010年入选教育部“新世纪优秀人才支持计划”，2013年1月获“青年科学之星铜奖”，2014年担任中国生物工程学会计算生物学与生物信息学专业委员会的副主任委员，2015年入选“青年拔尖人才支持计划”。

 内容摘要：
Post-translational modification of proteins provides reversible means to regulate the function of a protein in space and time. Recently, mass spectrometry-based proteomic profiling of PTMs has emerged to be a hot topic, and computational analyses of the flood of data have attracted much attention. In 2008, we developed a GPS (Group-based Prediction System, http://gps.biocuckoo.org) algorithm, which can predict kinase-specific phosphorylation sites for 408 human protein kinases in hierarchy. Together with this sequence-based algorithm and protein-protein interaction information, we further developed a software package of iGPS (“in vivo” GPS, http://igps.biocuckoo.org) for predicting potential site-specific kinase-substrate relations (ssKSRs) and re-constructing phosphorylation networks. From the results, we observed that the eukaryotic phosphoregulation is poorly conserved at the site and substrate levels, but preferentially conserved at the pathway levels. Also, we performed a systematic prediction of POLO-like kinase (Plk)-specific phosphor-binding and phosphorylation sites from phosphoproteomic data, and experimentally validated that human Mis18B is a novel interacting partner of Plk1. Based on a simple hypothesis that a kinase with higher activity phosphorylates more sites, we further developed an algorithm of kinase activity analysis (KAA) to monitor differentially active kinases among different tissues. Together with phosphoproteomic identifications, we re-constructed phosphorylation networks for mouse testis. By comparing to other tissues, we observed that a number of kinases such as POLO-like kinases (Plks), MAPKs, and CDKs with statistically more ssKSRs might have significantly higher activities, while the prediction was experimentally validated by detecting and comparing the activity-associated phosphorylation of Plk1 in testis and other tissues. Further experiments showed that the inhibition of Plk1 decreases cell proliferation by inducing G2/M cell cycle arrest. Taken together, our studies not only provided useful tool for analyzing the phosphoproteomic data, but also the prediction results are accurate for further experimental manipulation.