The ENPKG workflow requires LC-HRMS 2 DDA data and associated metadata as input. LC-HRMS 2 DDA data can be obtained in two ways: directly generated by researchers (Figure A1. Data generation) or by reusing published datasets (Figure A2 Data reuse). In both cases, the data for each sample are processed to perform feature detection and export the resulting files (Figure , step 1), here, using MZmine . The MS data files -the raw LC-HRMS 2 data (.mzML format) and the features' MS 2 spectra (.mgf) files -are then uploaded to a MassIVE repository (Figure B, step 2b), hence allowing the complete MS dataset to benefit from a global DOI and to attribute to each MSMS spectrum its corresponding Universal Spectrum Identifier (USI) . This mechanism allows efficient referencing, sharing, and observation of spectra, but also LC-HRMS 2 profiles, through the GNPS dashboard, and in the end, facilitates their publication and reuse . In addition, we generated four links allowing to perform, for each individual spectrum of the ENPKG, a direct or analog spectral search against the GNPS libraries or the GNPS data index through the Fasst Search interface (). In addition to the MS data, the minimal sufficient metadata should contain: the LC-HRMS The data present in each directory are then processed as follows: 1) taxonomical standardization of the samples' provided biosource using OpenTree and OTT, and reconciliation with external identifiers in Wikidata , 2) a local implementation of FBMN using the matchms package , 3) chemical structure annotation using in silico database of natural products (ISDB-LOTUS) matching along with taxonomical and chemical consistency reweighting , and 4) chemical structure and chemical class annotation using SIRIUS/CSI:FingerID and CANOPUS, respectively (Figure B, steps 3 to 6). Comparing structural annotations results from two different approaches (here ISDB-LOTUS and SIRIUS) allows the user to strengthen confidence in spectral annotation(s) -if both outputs are structurally similar -or penalize annotation(s)