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bioRxiv · 10.1101/2023.11.30.569448

PROTEOME-SCALE RECOMBINANT STANDARDS AND A ROBUST HIGH-SPEED SEARCH ENGINE TO ADVANCE CROSS-LINKING MS-BASED INTERACTOMICS

Clasen, M. A.·Ruwolt, M.·Kurt, L. U.·Gozzo, F. C.·Wang, S.·Chen, T.·Carvalho, P. C.·Lima, D. B.·Liu, F.
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Abstract

AO_SCPLOWBSTRACTC_SCPLOWAdvancing data analysis tools for proteome-wide cross-linking mass spectrometry (XL-MS) requires ground-truth standards that mimic biological complexity. Here, we develop wellcontrolled XL-MS standards comprising hundreds of recombinant proteins that are systematically mixed for cross-linking. We use one standard dataset to guide the development of Scout, a search engine for XL-MS with MS-cleavable cross-linkers. Using other, independent datasets from our standards as well as published datasets, we benchmark the performance of Scout and existing XL-MS software. This demonstrates that Scout offers the best combination of speed, sensitivity, and false-discovery rate control. These results illustrate how our large recombinant standards can support the development of XL-MS analysis tools and evaluation of XL-MS results.

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Clasen, M. A., Ruwolt, M., Kurt, L. U., Gozzo, F. C., Wang, S., Chen, T., Carvalho, P. C., Lima, D. B., Liu, F.. 2023-12-02. PROTEOME-SCALE RECOMBINANT STANDARDS AND A ROBUST HIGH-SPEED SEARCH ENGINE TO ADVANCE CROSS-LINKING MS-BASED INTERACTOMICS. https://doi.org/10.1101/2023.11.30.569448

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