Redesigning error control in cross-linking mass spectrometry enables more robust and sensitive protein-protein interaction studies.

ABSTRACT: Cross-linking mass spectrometry (XL-MS) allows characterizing protein-protein interactions (PPIs) in native biological systems by capturing cross-links between different proteins (inter-links). However, inter-link identification remains challenging, requiring dedicated data filtering schemes and thorough error control. Here, we benchmark existing data filtering schemes combined with error rate estimation strategies utilizing concatenated target-decoy protein sequence databases. These workflows show shortcomings either in sensitivity (many false negatives) or specificity (many false positives). To ameliorate the limited sensitivity without compromising specificity, we develop an alternative target-decoy search strategy using fused target-decoy databases. Furthermore, we devise a different d

SUBMITTER: Bogdanow B 

PROVIDER: S-EPMC11696718 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature