鸟枪法蛋白质鉴定质量控制方法研究进展

鸟枪法串联质谱蛋白质鉴定策略由于其高可靠和高效率而被广泛应用于蛋白质组学研究中，这种方法直接对蛋白质混合物进行酶切，以肽段为鉴定单元，继而推导真实的样品蛋白质．由于利用质谱图推导肽段存在一定的假阳性率，而且直接对蛋白质混合物的酶切也导致了肽段和蛋白质之间关联信息的丢失，所鉴定的蛋白质难免存在部分不可靠结果．因此，蛋白质鉴定的质量控制在蛋白质组学研究中极为重要．蛋白质鉴定的质量控制包含两大类主要方法，其一为利用肽段进行蛋白质组装，当前最常用也被证明最有效的方法是使用简约原则，即用最少的蛋白质解释所有鉴定肽段，现有的方法可以分为布尔型和概率型，其二为鉴定蛋白质的可靠性评估，包括单个蛋白质鉴定置信度和蛋白质鉴定整体水平的假阳性率计算．综合各种可辅助蛋白质鉴定的先验信息，构建普适的概率统计模型，是目前蛋白质鉴定质量控制方法的发展趋势．

The progress of protein quality control methods in shotgun proteomics

The shotgun strategy applying tandem mass spectrometry to identify proteins has been widely used in proteomics for its high reliability and efficiency. However, protein deduction is ambiguous due to uncorrected identified peptides and erased correlated information between peptides and their source proteins. Protein quality control methods can be divided into two categories: protein assembly and protein confidence evaluation. To date, parsimony principle, deriving the minimal proteins accounting for all identified peptides, has been widely used in protein assembly. Boolean and probability assembly are two kinds of methods in protein assembly. Protein confidence evaluation includes protein probability calculation of a single protein and false discovery rate estimation of all identified proteins. This review reveals the trend of developing a generalized probabilistic model with consideration of all influence factors, which can be applicable to a variety of peptide scoring system for protein identification.