OpenPepXL: An Open-Source Tool for Sensitive Identification of Cross-Linked Peptides in XL-MS.
Protein cross-linking
XL-MS
crosslinking
protein structure
structural biology
tandem mass spectrometry
Journal
Molecular & cellular proteomics : MCP
ISSN: 1535-9484
Titre abrégé: Mol Cell Proteomics
Pays: United States
ID NLM: 101125647
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
20
06
2020
revised:
15
09
2020
pubmed:
18
10
2020
medline:
12
8
2021
entrez:
17
10
2020
Statut:
ppublish
Résumé
Cross-linking MS (XL-MS) has been recognized as an effective source of information about protein structures and interactions. In contrast to regular peptide identification, XL-MS has to deal with a quadratic search space, where peptides from every protein could potentially be cross-linked to any other protein. To cope with this search space, most tools apply different heuristics for search space reduction. We introduce a new open-source XL-MS database search algorithm, OpenPepXL, which offers increased sensitivity compared with other tools. OpenPepXL searches the full search space of an XL-MS experiment without using heuristics to reduce it. Because of efficient data structures and built-in parallelization OpenPepXL achieves excellent runtimes and can also be deployed on large compute clusters and cloud services while maintaining a slim memory footprint. We compared OpenPepXL to several other commonly used tools for identification of noncleavable labeled and label-free cross-linkers on a diverse set of XL-MS experiments. In our first comparison, we used a data set from a fraction of a cell lysate with a protein database of 128 targets and 128 decoys. At 5% FDR, OpenPepXL finds from 7% to over 50% more unique residue pairs (URPs) than other tools. On data sets with available high-resolution structures for cross-link validation OpenPepXL reports from 7% to over 40% more structurally validated URPs than other tools. Additionally, we used a synthetic peptide data set that allows objective validation of cross-links without relying on structural information and found that OpenPepXL reports at least 12% more validated URPs than other tools. It has been built as part of the OpenMS suite of tools and supports Windows, macOS, and Linux operating systems. OpenPepXL also supports the MzIdentML 1.2 format for XL-MS identification results. It is freely available under a three-clause BSD license at https://openms.org/openpepxl.
Identifiants
pubmed: 33067342
pii: S1535-9476(20)60018-4
doi: 10.1074/mcp.TIR120.002186
pmc: PMC7710140
pii:
doi:
Substances chimiques
Cross-Linking Reagents
0
Peptides
0
Banques de données
PDB
['3GJX', '4F5S']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2157-2168Informations de copyright
© 2020 Netz et al.
Déclaration de conflit d'intérêts
Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article.
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