Cross-ID

Cross-ID visualizes and analyzes protein interaction networks derived from cross-linking mass spectrometry (XL-MS) data to map cross-links, post-translational modifications, domains, secondary structure, and functional annotations for structural interpretation and validation.

Key Features:

• Direct integration with XlinkX output: Parses XlinkX results generated for Proteome Discoverer to incorporate identified cross-links into downstream analyses.
• Text-file import: Accepts flexible tabular text inputs to incorporate XL-MS results from additional sources without format conversion.
• Grouping and spectral viewer: Organizes cross-links and provides spectral-level visualization for inspection of identified cross-linked peptides.
• Gene Ontology (GO) enrichment analysis: Performs GO-based enrichment to associate identified proteins with biological processes, cellular components, and molecular functions.
• Post-translational modification (PTM) visualization: Maps and displays PTMs on identified proteins and cross-linked sites.
• Domains and secondary structure mapping: Maps cross-links onto protein domains and annotated secondary-structure elements for structural context.
• Data set comparison: Compares multiple XL-MS datasets to identify consistent or divergent cross-linking patterns across experiments.
• Previsualization overlap check: Evaluates overlapping data points prior to final visualization to ensure accurate representation of cross-links.
• Validation tools: Validates detected cross-links against known protein structures or via the DisVis online service (http://milou.science.uu.nl/cgi/services/DISVIS/disvis/).
• Export capabilities: Exports figures as PDF and exports underlying datasets as tab-separated text files for downstream analysis.

Scientific Applications:

• Protein interaction network characterization: Enables mapping of inter- and intra-protein cross-links to define interaction topologies within complexes.
• Structural interpretation of cross-links: Supports mapping of cross-links onto domains and secondary structures to assess spatial restraints and conformations.
• Functional annotation: Uses GO enrichment and PTM mapping to link cross-linked proteins to cellular processes and regulatory modification states.
• Comparative XL-MS studies: Facilitates comparison across datasets to identify reproducible interactions or condition-specific changes.
• Disease and drug discovery research: Provides structural and interaction-level data to inform studies of disease mechanisms and target characterization.

Methodology:

Parses XlinkX output and imported text files, maps cross-links and PTMs to protein sequences, performs GO enrichment, visualizes spectra, domains, and secondary structure, conducts dataset comparisons and overlap checks, validates cross-links against known structures or via DisVis, and exports figures as PDF and data as tab-separated text files.