Mono- and Intralink Filter (Mi-Filter) To Reduce False Identifications in Cross-Linking Mass Spectrometry Data


Chen X, Sailer C, Kammer KM, Fürsch J, Eisele MR, Sakata E, Pellarin R, Stengel F


Analytical Chemistry


Anal. Chem. 2022, 94, 51, 17751–17756.


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. In this article, we describe a mono- and intralink filter (mi-filter) that is applicable to any kind of cross-linking data and workflow. It stipulates that only proteins for which at least one monolink or intra-protein cross-link has been identified within a given data set 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 cross-linking data ranging from individual protein complexes over medium-complexity affinity enrichments to proteome-wide cell lysates and significantly reduces the number of false-positive identifications for inter-protein links in all these types of XL-MS data.


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