PTMiner: Localization and Quality Control of Protein Modifications Detected in an Open Search and Its Application to Comprehensive Post-translational Modification Characterization in Human Proteome | |
An, Zhiwu1,5; Zhai, Linhui2; Ying, Wantao3,4; Qian, Xiaohong3,4; Gong, Fuzhou1,5; Tan, Minjia2; Fu, Yan1,5 | |
刊名 | MOLECULAR & CELLULAR PROTEOMICS |
2019-02-01 | |
卷号 | 18期号:2页码:391-405 |
ISSN号 | 1535-9476 |
DOI | 10.1074/mcp.RA118.000812 |
通讯作者 | Gong, Fuzhou(fzgong@amt.ac.cn) ; Tan, Minjia(mjtan@simm.ac.cn) ; Fu, Yan(yfu@amss.ac.cn) |
英文摘要 | The open (mass tolerant) search of tandem mass spectra of peptides shows great potential in the comprehensive detection of post-translational modifications (PTMs) in shotgun proteomics. However, this search strategy has not been widely used by the community, and one bottleneck of it is the lack of appropriate algorithms for automated and reliable post-processing of the coarse and error-prone search results. Here we present PTMiner, a software tool for confident filtering and localization of modifications (mass shifts) detected in an open search. After mass-shift-grouped false discovery rate (FDR) control of peptide-spectrum matches (PSMs), PTMiner uses an empirical Bayesian method to localize modifications through iterative learning of the prior probabilities of each type of modification occurring on different amino acids. The performance of PTMiner was evaluated on three data sets, including simulated data, chemically synthesized peptide library data and modified-peptide spiked-in proteome data. The results showed that PTMiner can effectively control the PSM FDR and accurately localize the modification sites. At 1% real false localization rate (FLR), PTMiner localized 93%, 84 and 83% of the modification sites in the three data sets, respectively, far higher than two open search engines we used and an extended version of the Ascore localization algorithm. We then used PTMiner to analyze a draft map of human proteome containing 25 million spectra from 30 tissues, and confidently identified over 1.7 million modified PSMs at 1% FDR and 1% FLR, which provided a system-wide view of both known and unknown PTMs in the human proteome. |
资助项目 | National Key Basic Research Program of China[2017YFC0908400] ; National Key Basic Research Program of China[2017YFC0906600] ; National Key Basic Research Program of China[2015CB554406] ; Natural Science Foundation of China[81872888] ; Natural Science Foundation of China[31670066] ; Natural Science Foundation of China[31700724] ; Natural Science Foundation of China[91630314] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB13040600] ; International SAMP;T Cooperation Program of China[2014DFB30010] ; NCMIS CAS |
WOS关键词 | PHOSPHORYLATION SITE LOCALIZATION ; MASS-SPECTROMETRY ; PEPTIDE IDENTIFICATION ; SHOTGUN PROTEOMICS ; TANDEM ; MS/MS ; ALGORITHM ; DISCOVERY ; SOFTWARE ; ACCURATE |
WOS研究方向 | Biochemistry & Molecular Biology |
语种 | 英语 |
出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
WOS记录号 | WOS:000457454000016 |
内容类型 | 期刊论文 |
源URL | [http://119.78.100.183/handle/2S10ELR8/290581] |
专题 | 中国科学院上海药物研究所 |
通讯作者 | Gong, Fuzhou; Tan, Minjia; Fu, Yan |
作者单位 | 1.Chinese Acad Sci, Acad Math & Syst Sci, Natl Ctr Math & Interdisciplinary Sci, Key Lab Random Complex Struct & Data Sci, Beijing 100190, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Natl Engn Res Ctr Prot Drugs, Beijing Proteome Res Ctr, Natl Ctr Prot Sci Beijing, State Key Lab Prote, Beijing 102206, Peoples R China 4.Beijing Inst Life, Beijing 100850, Peoples R China 5.Univ Chinese Acad Sci, Sch Math Sci, Beijing 100049, Peoples R China |
推荐引用方式 GB/T 7714 | An, Zhiwu,Zhai, Linhui,Ying, Wantao,et al. PTMiner: Localization and Quality Control of Protein Modifications Detected in an Open Search and Its Application to Comprehensive Post-translational Modification Characterization in Human Proteome[J]. MOLECULAR & CELLULAR PROTEOMICS,2019,18(2):391-405. |
APA | An, Zhiwu.,Zhai, Linhui.,Ying, Wantao.,Qian, Xiaohong.,Gong, Fuzhou.,...&Fu, Yan.(2019).PTMiner: Localization and Quality Control of Protein Modifications Detected in an Open Search and Its Application to Comprehensive Post-translational Modification Characterization in Human Proteome.MOLECULAR & CELLULAR PROTEOMICS,18(2),391-405. |
MLA | An, Zhiwu,et al."PTMiner: Localization and Quality Control of Protein Modifications Detected in an Open Search and Its Application to Comprehensive Post-translational Modification Characterization in Human Proteome".MOLECULAR & CELLULAR PROTEOMICS 18.2(2019):391-405. |
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