ArticleMolecular & cellular proteomics : MCP2020
MaXLinker: Proteome-wide Cross-link Identifications with High Specificity and Sensitivity.
Article in Molecular & cellular proteomics : MCP, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- To cleave or not to cleave: a systemic evaluation of DSS versus DSSO for cross-linking mass spectrometry analysis.Molecular systems biology · 2026Article
- Integrative structure determination of a human mitochondrial contact site and cristae organizing system (MICOS) sub-assembly.bioRxiv : the preprint server for biology · 2026Article
- Cysteine-enabled cleavability to advance cross-linking mass spectrometry for global analysis of endogenous protein-protein interactions.Nature communications · 2025Article
- Breaking barriers in crosslinking mass spectrometry with enhanced throughput and sensitivity using Orbitrap Astral.Nature communications · 2025Article
- In vivo crosslinking and effective 2D enrichment for proteome wide interactome studies.Communications chemistry · 2025Article
- Trioxane-based MS-cleavable cross-linking mass spectrometry for profiling multimeric interactions of cellular networks.Nature communications · 2025Article
- Developing a new cleavable crosslinker reagent for in-cell crosslinking.Communications chemistry · 2025Article
- DSBSO-Based XL-MS Analysis of Breast Cancer PDX Tissues to Delineate Protein Interaction Network in Clinical Samples.Journal of proteome research · 2024Article
- Characterizing lysinoalanine crosslinks in food systems: Discovery of a diagnostic ion in model peptides using MALDI mass spectrometry.Food chemistry: X · 2023Article
- New advances in cross-linking mass spectrometry toward structural systems biology.Current opinion in chemical biology · 2023Review
- MS Annika 2.0 Identifies Cross-Linked Peptides in MS2-MS3-Based Workflows at High Sensitivity and Specificity.Journal of proteome research · 2023Article
- Exploring an Alternative Cysteine-Reactive Chemistry to Enable Proteome-Wide PPI Analysis by Cross-Linking Mass Spectrometry.Analytical chemistry · 2023Article
- In-Cell Labeling and Mass Spectrometry for Systems-Level Structural Biology.Chemical reviews · 2022Review
- Two-Dimensional Fractionation Method for Proteome-Wide Cross-Linking Mass Spectrometry Analysis.Analytical chemistry · 2022Article
- Developing a Targeted Quantitative Strategy for Sulfoxide-Containing MS-Cleavable Cross-Linked Peptides to Probe Conformational Dynamics of Protein Complexes.Analytical chemistry · 2022Article
- Handcuffing intrinsically disordered regions in Mlh1-Pms1 disrupts mismatch repair.Nucleic acids research · 2021Article
- Protein interaction landscapes revealed by advanced in vivo cross-linking-mass spectrometry.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Structural basis of TRAPPIII-mediated Rab1 activation.The EMBO journal · 2021Article
- Reliable identification of protein-protein interactions by crosslinking mass spectrometry.Nature communications · 2021Article
- Crosslinking mass spectrometry: A link between structural biology and systems biology.Protein science : a publication of the Protein Society · 2021Review
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10 authors.
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Abstract
Protein-protein interactions play a vital role in nearly all cellular functions. Hence, understanding their interaction patterns and three-dimensional structural conformations can provide crucial insights about various biological processes and underlying molecular mechanisms for many disease phenotypes. Cross-linking mass spectrometry (XL-MS) has the unique capability to detect protein-protein interactions at a large scale along with spatial constraints between interaction partners. The inception of MS-cleavable cross-linkers enabled the MS2-MS3 XL-MS acquisition strategy that provides cross-link information from both MS2 and MS3 level. However, the current cross-link search algorithm available for MS2-MS3 strategy follows a "MS2-centric" approach and suffers from a high rate of mis-identified cross-links. We demonstrate the problem using two new quality assessment metrics ["fraction of mis-identifications" (FMI) and "fraction of interprotein cross-links from known interactions" (FKI)]. We then address this problem, by designing a novel "MS3-centric" approach for cross-link identification and implementing it as a search engine named MaXLinker. MaXLinker outperforms the currently popular search engine with a lower mis-identification rate, and higher sensitivity and specificity. Moreover, we performed human proteome-wide cross-linking mass spectrometry using K562 cells. Employing MaXLinker, we identified a comprehensive set of 9319 unique cross-links at 1% false discovery rate, comprising 8051 intraprotein and 1268 interprotein cross-links. Finally, we experimentally validated the quality of a large number of novel interactions identified in our study, providing a conclusive evidence for MaXLinker's robust performance.
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