Česká společnost pro hmotnostní spektrometrii

(13. ročník České konference hmotnostní spektrometrie a 11. Neformální proteomické setkání - WeS-05)
Mass Spectral Library Network (MERLIN) To Streamline The Generation Of Public Spectral Libraries

Federico Brigante ^1 *, Corinna Brungs ², Filip Jozefov ¹, Tomas Pluskal ¹

1. Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Czech Republic
2. Faculty of Life Sciences, University of Vienna, Austria

Abstrakt

When solving a research question, we deal with a matrix of interest and the analytical technique will detect certain metabolites that will be identified to answer our questions. With an estimated ~10^60 small molecules [1], assigning a spectrum to its correct structure is inherently challenging. Natural products further complicate this task, as they often occur at low concentrations and feature complex scaffolds and stereochemistry. As a result, confident identification depends on high-quality reference mass spectral libraries. However, current open libraries lack chemical coverage or provide only MS^2 fragmentation, they are high-priced; or their use is restricted for specific applications [2]. This motivates the creation of an open-source, multi-stage MS^n library in which molecules are fragmented in successive rounds, rather than in a single stage, to reveal deeper structural layers and enhance molecular annotation. Importantly, this approach remains fully compatible with existing MS^2 workflows. The first stage of the MERLIN initiative, the MSnLib project [3], introduced the workflow for data cleanup, sample preparation, acquisition using a flow injection system coupled to an Orbitrap mass analyzer, and data processing for MSn (where 2<n≤5) library generation of 30,000 compounds. These are already available for download and integration into metabolomics workflows. Currently, the second stage of the initiative involves a substantial expansion of the coverage. Using the established workflow, 163,000 compounds have been measured during 2025 and an extra 97,000 compounds will be measured by 2026, being the largest open-source MSn library up to date.

* Korespondující autor: federico_ivan.brigante@uochb.cas.cz

Literatura

1. Franco, L. S., de Jesus, B. D. S. M, Pinheiro, P. S. M., Fraga, C. A. M., (2024), Remapping the Chemical Space and the Pharmacological Space of Drugs: What Can We Expect from the Road Ahead?, Pharmaceuticals (Basel), doi: 10.3390/ph17060742.
2. Li, G., Peng, X., Guo, Y., Gong, S., Cao, S. and Qiu, F., (2021), Currently Available Strategies for Target Identification of Bioactive Natural Products, Frontiers in Chemistry, doi: 10.3389/fchem.2021.761609
3. Brungs, C., Schmid, R., Heuckeroth, S. et al. (2025), MSnLib: efficient generation of open multi-stage fragmentation mass spectral libraries, Nat Methods, doi: 10.1038/s41592-025-02813-0