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A high-speed search engine pLink 2 with systematic evaluation for proteome-scale identification of cross-linked peptides

Open access
Chen, Zhen-Lin, Meng, Jia-Ming, Cao, Yong, Yin, Ji-Li, Fang, Run-Qian, Fan, Sheng-Bo, Liu, Chao, Zeng, Wen-Feng, Ding, Yue-He, Tan, Dan, Wu, Long, Zhou, Wen-Jing, Chi, Hao, Sun, Rui-Xiang, Dong, Meng-Qiu, He, Si-Min·2019·Nature Communications

Abstract

We describe pLink 2, a search engine with higher speed and reliability for proteome-scale identification of cross-linked peptides. With a two-stage open search strategy facilitated by fragment indexing, pLink 2 is ~40 times faster than pLink 1 and 3~10 times faster than Kojak. Furthermore, using simulated datasets, synthetic datasets, 15 N metabolically labeled datasets, and entrapment databases, four analysis methods were designed to evaluate the credibility of ten state-of-the-art search engines. This systematic evaluation shows that pLink 2 outperforms these methods in precision and sensitivity, especially at proteome scales. Lastly, re-analysis of four published proteome-scale cross-linking datasets with pLink 2 required only a fraction of the time used by pLink 1, with up to 27% more cross-linked residue pairs identified. pLink 2 is therefore an efficient and reliable tool for cross-linking mass spectrometry analysis, and the systematic evaluation methods described here will be useful for future software development.

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Metadata

Authors
Chen, Z.-L., Meng, J.-M., Cao, Y., Yin, J.-L., Fang, R.-Q., Fan, S.-B., Liu, C., Zeng, W.-F., Ding, Y.-H., Tan, D., Wu, L., Zhou, W.-J., Chi, H., Sun, R.-X., Dong, M.-Q., & He, S.-M.
Venue
Nature Communications
Published
2019-07-30
Volume
10
Issue
1
Pages
3404-3404
ISSN
2041-1723 (ISSN-L)
OpenAlex
W2966215858
Cited by
552
References
6
FWCI
20.18
Type
journal article
Language
en
Open access
gold

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Chen, Z.-L., Meng, J.-M., Cao, Y., Yin, J.-L., Fang, R.-Q., Fan, S.-B., Liu, C., Zeng, W.-F., Ding, Y.-H., Tan, D., Wu, L., Zhou, W.-J., Chi, H., Sun, R.-X., Dong, M.-Q., & He, S.-M. (2019). A high-speed search engine pLink 2 with systematic evaluation for proteome-scale identification of cross-linked peptides. Nature Communications. https://doi.org/10.1038/s41467-019-11337-z

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