Fast and accurate identification of semi-tryptic peptides in shotgun proteomics
Fast and accurate identification of semi-tryptic peptides in shotgun proteomics
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DOI：
10.1093/bioinformatics/btm545
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发表时间：
2008-01-01
期刊：
影响因子：
5.8
通讯作者：
Radivojac, Predrag
中科院分区：
文献类型：
--
作者：
Alves, Pedro;Arnold, Randy J.;Radivojac, Predrag
动机：鸟枪式蛋白质组学的主要问题之一是在分析复杂蛋白质样本时肽覆盖率较低。识别更多的多肽，例如非胰蛋白酶多肽，可以增加多肽的覆盖率，并改进基于多肽鉴定结果的蛋白质鉴定和/或量化。然而，从复杂的样本中搜索所有潜在的非胰蛋白酶多肽是一项耗时的工作，也给常规的数据分析带来了挑战。结果：我们假设非胰蛋白酶多肽主要是在分离前截断规则的胰多肽而产生的。我们引入了胰蛋白酶多肽可转移性的概念，即以其截断形式识别多肽的概率，并建立了一个预测器来从其序列中估计多肽的转移性。我们表明，我们的预测达到了有用的准确性，ROC曲线下的面积从76到87，并且可以用于筛选序列数据库来识别截短肽。经过过滤后，只保留有限数量的具有最高可转化率的胰蛋白肽用于非胰蛋白肽的搜索。通过将该方法应用于半胰蛋白酶多肽的鉴定，我们表明，在与胰蛋白酶多肽鉴定相当的搜索时间内可以鉴定出相当数量的这类多肽。
Motivation: One of the major problems in shotgun proteomics is the low peptide coverage when analyzing complex protein samples. Identifying more peptides, e.g. non-tryptic peptides, may increase the peptide coverage and improve protein identification and/or quantification that are based on the peptide identification results. Searching for all potential non-tryptic peptides is, however, time consuming for shotgun proteomics data from complex samples, and poses a challenge for a routine data analysis.Results: We hypothesize that non-tryptic peptides are mainly created from the truncation of regular tryptic peptides before separation. We introduce the notion of truncatability of a tryptic peptide, i.e. the probability of the peptide to be identified in its truncated form, and build a predictor to estimate a peptides truncatability from its sequence. We show that our predictions achieve useful accuracy, with the area under the ROC curve from 76 to 87, and can be used to filter the sequence database for identifying truncated peptides. After filtering, only a limited number of tryptic peptides with the highest truncatability are retained for non-tryptic peptide searching. By applying this method to identification of semi-tryptic peptides, we show that a significant number of such peptides can be identified within a searching time comparable to that of tryptic peptide identification.