title: Top-down protein identification using isotopic envelope fingerprinting.
abstract: For top-down protein database search and identification from tandem mass spectra, our isotopic envelope fingerprinting search algorithm and ProteinGoggle search engine have demonstrated their strength of efficiently resolving heavily overlapping data as well separating non-ideal data with non-ideal isotopic envelopes from ideal ones with ideal isotopic envelopes. Here we report our updated ProteinGoggle 2.0 for intact protein database search with full-capacity. The indispensable updates include users' optional definition of dynamic post-translational modifications and static chemical labeling during database creation, comprehensive dissociation methods and ion series, as well as a Proteoform Score for each proteoform. ProteinGoggle has previously been benchmarked with both collision-based dissociation (CID, HCD) and electron-based dissociation (ETD) data of either intact proteins or intact proteomes. Here we report our further benchmarking of the new version of ProteinGoggle with publically available photon-based dissociation (UVPD) data (http://hdl.handle.net/2022/17316) of intact E. coli ribosomal proteins.
  
  
  
  Protein species (aka proteoforms) function at their molecular level, and diverse structures and biological roles of every proteoform come from often co-occurring proteolysis, amino acid variation and post-translational modifications. Complete and high-throughput capture of this combinatorial information of proteoforms has become possible in evolving top-down proteomics; yet, various methods and technologies, especially database search and bioinformatics identification tools, in the top-down pipeline are still in their infancy stages and demand intensive research and development.
authors.affiliation: School of Chemical Science and Engineering, Tongji University, Shanghai, China; Shanghai Key Laboratory of Chemical Assessment and Sustainability, Tongji University, Shanghai, China.
authors.forename: Kaijie
authors.initials: K
authors.lastname: Xiao
authors.affiliation: School of Chemical Science and Engineering, Tongji University, Shanghai, China; Shanghai Key Laboratory of Chemical Assessment and Sustainability, Tongji University, Shanghai, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yu
authors.affiliation: School of Chemical Science and Engineering, Tongji University, Shanghai, China; Shanghai Key Laboratory of Chemical Assessment and Sustainability, Tongji University, Shanghai, China. Electronic address: zhixintian@tongji.edu.cn.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Tian
mesh_terms: D000465:Algorithms; D001426:Bacterial Proteins; D030562:Databases, Protein / Q000592:standards*; D004926:Escherichia coli / Q000737:chemistry; D010449:Peptide Mapping / Q000379:methods*; D011499:Protein Processing, Post-Translational; D020543:Proteome; D012269:Ribosomal Proteins / Q000032:analysis; D057386:Search Engine / Q000379:methods* / Q000592:standards
chemical_list: D001426:Bacterial Proteins; D020543:Proteome; D012269:Ribosomal Proteins
keywords: Intact protein; Intact proteome; Isotopic envelope fingerprinting; Post-translational modifications; Protein database search; Protein identification; Protein species; Proteoform; Top-down; UVPD