Improved Peptide Identification for Proteomic Analysis Based on Comprehensive Characterization of Electron Transfer Dissociation Spectra

doi:10.1021/pr100648r

	Improved Peptide Identification for Proteomic Analysis Based on Comprehensive Characterization of Electron Transfer Dissociation Spectra
	Sun, Rui-Xiang 1; Dong, Meng-Qiu 2; Song, Chun-Qing 2; Chi, Hao 1; Yang, Bing 2; Xiu, Li-Yun 1; Tao, Li 2; Jing, Ziu-Yi 2; Liu, Chao 1; Wang, Le-Heng 1; Fu, Yan 1; He, Si-Min 1
	2010-12-01
发表期刊	JOURNAL OF PROTEOME RESEARCH
ISSN	1535-3893
卷号	9 期号:12 页码:6354-6367
摘要	In recent years, electron transfer dissociation (ETD) has enjoyed widespread applications from sequencing of peptides with or without post-translational modifications to top-down analysis of intact proteins However peptide identification rates from ETD spectra compare poorly with those from collision induced dissociation (CID) spectra especially for doubly charged precursors This is in part due to an insufficient understanding of the characteristics of ETD and consequently a failure of database search engines to make use of the rich information contained in the ETD spectra In this study, we statistically characterized ETD fragmentation patterns from a collection of 461 440 spectra and subsequently implemented our findings into pFind a database search engine developed earlier for CID data From ETD spectra of doubly charged precursors pFind 2 1 identified 63-122% more unique peptides than Mascot 2 2 under the same 1% false discovery rate For higher charged peptides as well as phosphopeptides, pFind 2 1 also consistently obtained more identifications Of the features built into pFind 2 1, the following two greatly enhanced its performance (1) refined automatic detection and removal of high-intensity peaks belonging to the precursor charge-reduced precursor or related neutral loss species whose presence often set spectral matching askew, (2) a thorough consideration of hydrogen-rearranged fragment ions such as z + H and c - H for peptide precursors of different charge states Our study has revealed that different charge states of precursors result in different hydrogen rearrangement patterns For a fragment ion, its propensity of gaining or losing a hydrogen depends on (1) the ion type (c or z) and (2) the size of the fragment relative to the precursor and both dependencies are affected by (3) the charge state of the precursor In addition, we discovered ETD characteristics that are unique for certain types of amino acids (AAs), such as a prominent neutral loss of SCH(2)CONH(2) (90 0014 Da) from z ions with a carbamidomethylated cysteine at the N-terminus and a neutral loss of histidine side chain C(4)N(2)H(5) (81 0453 Da) from precursor ions containing histidine The comprehensive list of ETD characteristics summarized in this paper should be valuable for automated database search de novo peptide sequencing and manual spectral validation
关键词	ETD hydrogen rearrangement peptide sequencing search engine
DOI	10.1021/pr100648r
收录类别	SCI
语种	英语
资助项目	National High Technology Research and Development Program of China[2008AA02Z309] ; National High Technology Research and Development Program of China[2007AA02Z315] ; National High Technology Research and Development Program of China[2007AA02Z1A7] ; National Key Basic Research and Development Program of China[2010CB912701] ; CAS[KGGX1 YW 13] ; National Natural Science Foundation of China[30900262]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemical Research Methods
WOS记录号	WOS:000284856200024
出版者	AMER CHEMICAL SOC
引用统计	被引频次：39[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.204/handle/2XEOYT63/12141
专题	中国科学院计算技术研究所期刊论文_英文
通讯作者	Sun, Rui-Xiang
作者单位	1.Chinese Acad Sci, Inst Comp Technol, Key Lab Intelligent Informat Proc, Beijing 100190, Peoples R China 2.Natl Inst Biol Sci, Beijing 102206, Peoples R China
推荐引用方式 GB/T 7714	Sun, Rui-Xiang,Dong, Meng-Qiu,Song, Chun-Qing,et al. Improved Peptide Identification for Proteomic Analysis Based on Comprehensive Characterization of Electron Transfer Dissociation Spectra[J]. JOURNAL OF PROTEOME RESEARCH,2010,9(12):6354-6367.
APA	Sun, Rui-Xiang.,Dong, Meng-Qiu.,Song, Chun-Qing.,Chi, Hao.,Yang, Bing.,...&He, Si-Min.(2010).Improved Peptide Identification for Proteomic Analysis Based on Comprehensive Characterization of Electron Transfer Dissociation Spectra.JOURNAL OF PROTEOME RESEARCH,9(12),6354-6367.
MLA	Sun, Rui-Xiang,et al."Improved Peptide Identification for Proteomic Analysis Based on Comprehensive Characterization of Electron Transfer Dissociation Spectra".JOURNAL OF PROTEOME RESEARCH 9.12(2010):6354-6367.