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bioRxiv · 10.1101/2022.02.03.478943

A mono- and intralink filter (mi-filter) to improve false-discovery rates in cross-linking mass spectrometry data

Chen, X.·Sailer, C.·Kammer, K.-M.·Fuersch, J.·Eisele, M. R.·Sakata, E.·Stengel, F.
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Abstract

Cross-Linking Mass Spectrometry (XL-MS) has become an indispensable tool for the emerging field of systems structural biology over the recent years. However, the confidence in individual protein-protein interactions (PPIs) depends on the correct assessment of individual inter protein cross-links. This can be challenging, in particularly in samples where relatively few PPIs are detected, as is often the case in complex samples containing low abundant proteins or in in-vivo settings. In this manuscript we are describing a novel mono- and intralink filter (mi-filter) that is applicable to any kind of crosslinking data and workflow. It stipulates that only proteins for which at least one monolink or intra-protein crosslink has been identified within a given dataset are considered for an inter-protein cross-link and therefore participate in a PPI. We show that this simple and intuitive filter has a dramatic effect on different types of crosslinking-data ranging from single protein complexes, over medium-complexity affinity enrichments to proteome-wide cell lysates and significantly lowers the number of false-positive identifications resulting in improved false-discovery rates for inter-protein links in all these types of XL-MS data.

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Chen, X., Sailer, C., Kammer, K.-M., Fuersch, J., Eisele, M. R., Sakata, E., Stengel, F.. 2022-02-03. A mono- and intralink filter (mi-filter) to improve false-discovery rates in cross-linking mass spectrometry data. https://doi.org/10.1101/2022.02.03.478943

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