蛋白质相互作用生物信息学.ppt

蛋白质相互作用的生物信息学 高友鹤 蛋白质相互作用的生物信息学 实验数据 蛋白质相互作用数据库 高通量实验数据的验证 蛋白质相互作用网络 计算预测蛋白质相互作用 实验数据 蛋白质相互作用的知识来源于实验。 高通量地应用传统实验方法获取大量相互作用信息。 高通量的数据需要验证。 高通量实验方法 Yeast two-hybrid assay Benefits: in vivo. Don’t need pure proteins. Don’t need Ab. Drawbacks: only two proteins are tested at a time (no cooperative binding); it takes place in the nucleus, so many proteins are not in their native compartment; and it predicts possible interactions, but is unrelated to the physiological setting. Mass spectrometry of purified complexes Benefits: several members of a complex can be tagged, giving an internal check for consistency; and it detects real complexes in physiological settings. Drawbacks: it might miss some complexes that are not present under the given conditions; tagging may disturb complex formation; and loosely associated components may be washed off during purification. Correlated mRNA expression Benefits: it is an in vivo technique, albeit an indirect one; and it has much broader coverage of cellular conditions than other methods. Drawbacks: it is a powerful method for discriminating cell states or disease outcomes, but is a relatively inaccurate predictor of direct physical interaction; and it is very sensitive to parameter choices and clustering methods during analysis. Genetic interactions (synthetic lethality). Benefits: it is an in vivo technique, albeit an indirect one; and it is amenable to unbiased genome-wide screens. Drawbacks: not necessarily physical interactions 蛋白质相互作用的生物信息学 实验数据 蛋白质相互作用数据库 高通量实验数据的验证 蛋白质相互作用网络 计算预测蛋白质相互作用 蛋白质相互作用数据库 THE DIP DATABASE Database of Interacting Proteins The DIP database catalogs experimentally determined interactions between proteins. DIP相互作用的表达 DIP数据库结构 BIND：the Biomolecular Interaction Network Database 蛋白质相互作用的生物信息学 实验数据 蛋白质相互作用数据库 高通量实验数据的验证 蛋白质相互作用网络 计算预测蛋白质相互作用 高通量实验数据需要验证 与可信的数据相比 Expression Profile Reliability EPR IndexExpression Profile Reliability Index (EPR Index) evaluates the quality of a large