In a proteogenomic approach based on tandem mass spectrometry analysis of proteolytic peptide mixtures, customized exome or RNA-seq databases are employed for identifying protein sequence variants. However, the problem of variant peptide identification without personalized genomic data is important for a variety of applications. Following the recent proposal by Chick et al. (Nat. Biotechnol. 33, 743–749, 2015) on the feasibility of such variant peptide search, we evaluated two available approaches based on the previously suggested “open” search and the “brute-force” strategy. To improve the efficiency of these approaches, we propose an algorithm for exclusion of false variant identifications from the search results involving analysis of modifications mimicking single amino acid substitutions. Also, we propose a de novo based scoring scheme for assessment of identified point mutations. In the scheme, the search engine analyzes y-type fragment ions in MS/MS spectra to confirm the location of the mutation in the variant peptide sequence.

中文翻译：

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无需个人基因组数据的蛋白质组学中基于质谱的基于变种肽鉴定的蛮力法

在基于蛋白质水解肽混合物的串联质谱分析的蛋白质组学方法中，采用定制的外显子组或RNA-seq数据库来鉴定蛋白质序列变体。然而，没有个性化基因组数据的变体肽鉴定问题对于多种应用而言是重要的。根据Chick等人的最新提议。（NAT。生物技术。33，743-749，2015年）关于这种变体多肽搜索的可行性，我们基于先前建议的“开放”搜索和“强力”策略评估了两种可用的方法。为了提高这些方法的效率，我们提出了一种从搜索结果中排除错误变体识别的算法，该算法涉及对模拟单个氨基酸取代的修饰进行分析。此外，我们提出了一种从头开始的计分方案，用于评估已识别的点突变。在该方案中，搜索引擎分析MS / MS光谱中的y型片段离子，以确认突变在变体肽序列中的位置。