Scalability of mass spectrometry-based metabolomics for natural extracts libraries exploration: current status, challenges, and opportunities
ETH Zürich 
Wout Bittremieux 
University of Antwerp
Robin Schmid
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences
mzio GmbH
Olivier Cailloux
Université Paris-Dauphine, Université PSL
Justin J. J. van der Hooft
Wageningen University & Research
University of Johannesburg
Université Paris-Saclay
This review explores the potential of bioinformatics and chemoinformatics tools to advance the exploration of natural extracts libraries (NELs). Although metabolomics has become a term used routinely in natural product (NP) research, the field remains focused on individual molecules or small sets of compounds, which restricts scalability. This narrow focus is mirrored in the computational handling of generated data, limiting broader insights. By challenging the traditional molecule-first paradigm—a framework historically shaped by practical constraints—we present our vision of using computational approaches to unlock the full potential of NELs, now and in the future.