title: Reprint of "pFind-Alioth: A novel unrestricted database search algorithm to improve the interpretation of high-resolution MS/MS data".
abstract: Database search is the dominant approach in high-throughput proteomic analysis. However, the interpretation rate of MS/MS spectra is very low in such a restricted mode, which is mainly due to unexpected modifications and irregular digestion types. In this study, we developed a new algorithm called Alioth, to be integrated into the search engine of pFind, for fast and accurate unrestricted database search on high-resolution MS/MS data. An ion index is constructed for both peptide precursors and fragment ions, by which arbitrary digestions and a single site of any modifications and mutations can be searched efficiently. A new re-ranking algorithm is used to distinguish the correct peptide-spectrum matches from random ones. The algorithm is tested on several HCD datasets and the interpretation rate of MS/MS spectra using Alioth is as high as 60%-80%. Peptides from semi- and non-specific digestions, as well as those with unexpected modifications or mutations, can be effectively identified using Alioth and confidently validated using other search engines. The average processing speed of Alioth is 5-10 times faster than some other unrestricted search engines and is comparable to or even faster than the restricted search algorithms tested.This article is part of a Special Issue entitled: Computational Proteomics.
authors.affiliation: Key Lab of Intelligent Information Processing of Chinese Academy of Sciences (CAS), Institute of Computing Technology, CAS, Beijing 100190, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chi
authors.affiliation: Key Lab of Intelligent Information Processing of Chinese Academy of Sciences (CAS), Institute of Computing Technology, CAS, Beijing 100190, China.
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing 102206, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.affiliation: Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Key Lab of Intelligent Information Processing of Chinese Academy of Sciences (CAS), Institute of Computing Technology, CAS, Beijing 100190, China.
authors.forename: Rui-Xiang
authors.initials: RX
authors.lastname: Sun
authors.affiliation: Key Lab of Intelligent Information Processing of Chinese Academy of Sciences (CAS), Institute of Computing Technology, CAS, Beijing 100190, China.
authors.forename: Sheng-Bo
authors.initials: SB
authors.lastname: Fan
authors.affiliation: Key Lab of Intelligent Information Processing of Chinese Academy of Sciences (CAS), Institute of Computing Technology, CAS, Beijing 100190, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Key Lab of Intelligent Information Processing of Chinese Academy of Sciences (CAS), Institute of Computing Technology, CAS, Beijing 100190, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Key Lab of Intelligent Information Processing of Chinese Academy of Sciences (CAS), Institute of Computing Technology, CAS, Beijing 100190, China.
authors.forename: Zuo-Fei
authors.initials: ZF
authors.lastname: Yuan
authors.affiliation: Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China.
authors.forename: Quan-Hui
authors.initials: QH
authors.lastname: Wang
authors.affiliation: Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China.
authors.forename: Si-Qi
authors.initials: SQ
authors.lastname: Liu
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing 102206, China.
authors.forename: Meng-Qiu
authors.initials: MQ
authors.lastname: Dong
authors.affiliation: Key Lab of Intelligent Information Processing of Chinese Academy of Sciences (CAS), Institute of Computing Technology, CAS, Beijing 100190, China. Electronic address: smhe@ict.ac.cn.
authors.forename: Si-Min
authors.initials: SM
authors.lastname: He
keywords: High resolution MS/MS; In-depth interpretation; Ion index; Unrestricted database search