Benchmarking study reveals substantial error rate discrepancies across crosslinking mass spectrometry software, highlighting the necessity of validated algorithms for reliable interaction mapping.
We benchmarked eight software tools in crosslinking mass spectrometry (MS) to evaluate their accuracy in detecting protein-protein interactions. Whereas about half performed reliably, others reported up to 31-fold more false interactions than indicated by their reported false discovery rates. During this community-driven effort, we helped correct one of the poorer-performing tools. Our findings demonstrate that, with robust algorithms, crosslinking MS can deliver highly dependable insights into biological systems.
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Fischer et al. (2025) studied this question.
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