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bioRxiv · 10.1101/2023.07.19.549678

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

Bogdanow, B.·Wang, C.·Ruwolt, M.·Ruta, J.·Mühlberg, L.·Zeng, W.-F.·Elofsson, A.·Liu, F.
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Abstract

In 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.

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Bogdanow, B., Wang, C., Ruwolt, M., Ruta, J., Mühlberg, L., Zeng, W.-F., Elofsson, A., Liu, F.. 2023-07-19. Enhancing Inter-link Coverage in Cross-Linking Mass Spectrometry through Context-Sensitive Subgrouping and Decoy Fusion. https://doi.org/10.1101/2023.07.19.549678

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