A hybrid method for peptide identification using integer linear optimization, local database search, and quadrupole time-of-flight or OrbiTrap tandem mass spectrometry
A hybrid method for peptide identification using integer linear optimization, local database search, and quadrupole time-of-flight or OrbiTrap tandem mass spectrometry
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DOI：
10.1021/pr700577z
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发表时间：
2008-04-01
影响因子：
4.4
通讯作者：
Yates, John R., III
中科院分区：
文献类型：
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作者：
DiMaggio, Peter A., Jr.;Floudas, Christodoulos A.;Yates, John R., III
本文提出了一种通过从头整数线性优化、本地数据库搜索和串联质谱自动识别肽的新型混合方法。利用从头识别算法 PILOT1,2 的修改版本来构建准确的从头肽序列。本地数据库搜索工具 FASTA(3) 的修改版本用于针对非冗余蛋白质数据库查询这些从头预测，以解析候选序列中的任何低置信度氨基酸。通过使用分布式计算减轻了与执行多次对齐相关的计算负担。针对这种新的混合方法进行了广泛的计算研究，并针对一组 38 个四极杆飞行时间 (QTOF) 和 380 个 OrbiTrap 串联质谱与 MASCOT(4) 进行了比较。我们提出的 OrbiTrap 谱混合方法的结果也与经过训练用于高精度串联质谱的 PepNovo 的修改版本（5）以及基于标签的方法 InsPecT 进行了比较。（6）还使用 CIDentify（7）针对非冗余蛋白质数据库搜索了 PILOT 和 PepNovo 的 de novo 序列，以与我们修改 FASTA 实现的比对进行比较。比较研究表明，通过结合我们基于整数线性优化的从头方法和数据库驱动的搜索方法的优势，可以获得出色的肽鉴定准确性。
A novel hybrid methodology for the automated identification of peptides via de novo integer linear optimization, local database search, and tandem mass spectrometry is presented in this article. A modified version of the de novo identification algorithm PILOT1,2 is utilized to construct accurate de novo peptide sequences. A modified version of the local database search tool FASTA(3) is used to query these de novo predictions against the nonredundant protein database to resolve any low-confidence amino acids in the candidate sequences. The computational burden associated with performing several alignments is alleviated with the use of distributive computing. Extensive computational studies are presented for this new hybrid methodology, as well as comparisons with MASCOT(4) for a set of 38 quadrupole time-of-flight (QTOF) and 380 OrbiTrap tandem mass spectra. The results for our proposed hybrid method for the OrbiTrap spectra are also compared with a modified version of PepNovo,(5) which was trained for use on high-precision tandem mass spectra, and the tag-based method InsPecT.(6) The de novo sequences of PILOT and PepNovo are also searched against the nonredundant protein database using CIDentify(7) to compare with the alignments achieved by our modifications of FASTA. The comparative studies demonstrate the excellent peptide identification accuracy gained from combining the strengths of our de novo method, which is based on integer linear optimization, and database driven search methods.