Palo Alto Research Center, 3333 Coyote Hill Road, Palo Alto, California 94304, United States.
J Proteome Res. 2011 Dec 2;10(12):5296-301. doi: 10.1021/pr200780j. Epub 2011 Nov 7.
The target-decoy approach to estimating and controlling false discovery rate (FDR) has become a de facto standard in shotgun proteomics, and it has been applied at both the peptide-to-spectrum match (PSM) and protein levels. Current bioinformatics methods control either the PSM- or the protein-level FDR, but not both. In order to obtain the most reliable information from their data, users must employ one method when the number of tandem mass spectra exceeds the number of proteins in the database and another method when the reverse is true. Here we propose a simple variation of the standard target-decoy strategy that estimates and controls PSM and protein FDRs simultaneously, regardless of the relative numbers of spectra and proteins. We demonstrate that even if the final goal is a list of PSMs with a fixed low FDR and not a list of protein identifications, the proposed two-dimensional strategy offers advantages over a pure PSM-level strategy.
靶标-诱饵方法已成为 shotgun 蛋白质组学中估计和控制假发现率（FDR）的一种事实上的标准，并且已经在肽与谱匹配（PSM）和蛋白质水平上得到了应用。目前的生物信息学方法要么控制 PSM 水平的 FDR，要么控制蛋白质水平的 FDR，但不能同时控制两者。为了从他们的数据中获得最可靠的信息，当串联质谱的数量超过数据库中的蛋白质数量时，用户必须使用一种方法，而当相反的情况时，则必须使用另一种方法。在这里，我们提出了一种标准靶标-诱饵策略的简单变体，无论光谱和蛋白质的相对数量如何，都可以同时估计和控制 PSM 和蛋白质 FDR。我们证明，即使最终的目标是具有固定低 FDR 的 PSM 列表，而不是蛋白质鉴定列表，所提出的二维策略也优于纯 PSM 水平的策略。
