Enhancing Inter-link Coverage in Cross-Linking Mass Spectrometry through Context-Sensitive Subgrouping and Decoy Fusion

Author:

Bogdanow BorisORCID,Wang Cong,Ruwolt MaxORCID,Ruta Julia,Mühlberg LarsORCID,Zeng Wen-fengORCID,Elofsson ArneORCID,Liu Fan

Abstract

ABSTRACTIn cross-linking mass spectrometry, sensitivity and specificity in assigning mass spectra to cross-links between different proteins (inter-links) remains challenging. Here, we report on limitations of commonly used concatenated target-decoy searches and propose a target-decoy competition strategy on a fused database as a solution. Further, we capitalize on context-divergent error rates by implementing a novel context-sensitive subgrouping strategy. This approach increases inter-link coverage by ∼ 30 - 75 % across XL-MS datasets, maintains low error rates, and preserves structural accuracy.

Publisher

Cold Spring Harbor Laboratory

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