Open Science Approaches for Mass Spectrometry-Based Exposomics

Prof. Dr. Emma L. Schymanski (plus many, many colleagues and collaborators!) Environmental Cheminformatics Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg [email protected] / https://gitlab.com/uniluxembourg/lcsb/eci https://wwwen.uni.lu/lcsb/research/environmental_cheminformatics/ Open Science Approaches for Mass Spectrometry Based Exposomics Slides available at DOI: 10.5281/zenodo.17782420 37th Annual Lake Louise Tandem MS Workshop Lake Louise, Canada – December 3 to 6, 2025 Performing Exposomics Over Lifetimes 2 Source: Begoña Talavera Andújar, https://hdl.handle.net/10993/61575. Performing Exposomics Over Lifetimes 3 Source: Begoña Talavera Andújar, https://hdl.handle.net/10993/61575. Video: J. Perera. Fig. Arp, Aurich et al. 2023 DOI: 10.1021/acs.est.3c01735 Environmental Cheminformatics @ LCSB, Uni.lu FAIR chemical data Open source mass spectral library HRMS NTS TP workflows Slide inspired by B. Talavera Explore chemical space Browse transformations 4 Disease impacts 123 million The Vast Chemical Space of Exposomics … Numbers updated 1 Dec. 2025. Mod. from Escher et al (2020). Science. DOI: 10.1126/science.aay6636 Image: ESO/IDA/Danish 1.5 m http://www.eso.org/public/images/potw1015a/ 123 million 20,206 compounds < 0.01% of PubChem The Vast Chemical Space of Exposomics … Target Analysis Numbers updated 1 Dec. 2025. Mod. from Escher et al (2020). Science. DOI: 10.1126/science.aay6636 Image: ESO/IDA/Danish 1.5 m http://www.eso.org/public/images/potw1015a/ 123 million 20,206 compounds < 0.01% of PubChem The Vast Chemical Space of Exposomics … Numbers updated 1 Dec. 2025. Mod. from Escher et al (2020). Science. DOI: 10.1126/science.aay6636 Image: ESO/IDA/Danish 1.5 m http://www.eso.org/public/images/potw1015a/ https://massbank.eu/MassBank/ https://github.com/MassBank/MassBank-data/ Neumann et al. (2025) NAR, DOI:10.1093/nar/gkaf1193 123 million The Vast Chemical Space of Exposomics … 133,646 suspects Suspect Screening Target Analysis Numbers updated 1 Dec. 2025. Mod. from Escher et al (2020). Science. DOI: 10.1126/science.aay6636 Image: ESO/IDA/Danish 1.5 m http://www.eso.org/public/images/potw1015a/ 20,206 compounds < 0.01% of PubChem Gathering Expert Knowledge: NORMAN-SLE (WiP) 9 Grand Challenge: HR-MS “Chemical Space” is too Big! 290 million 123 million 129 million Candidates with high information content Candidates with low information content 1.25 million …and prohibitive run times! 16 Creating Informative Subsets of 17 Elapavalore et al. (2025) DOI: 10.1021/acs.estlett.4c01003 Schymanski et al. (2021) DOI: 10.1186/s13321-021-00489-0 Creating Informative Subsets of ~500,000 entries “small” Elapavalore et al. (2025) DOI: 10.1021/acs.estlett.4c01003 Schymanski et al. (2021) DOI: 10.1186/s13321-021-00489-0 18 Elapavalore et al. (2025) DOI: 10.1021/acs.estlett.4c01003 & Schymanski et al. (2021) DOI: 10.1186/s13321-021-00489-0 19 : Fewer and more relevant candidates – with context is a Dynamic Collection … •… built & evaluated every week, updated online every month •… growing as knowledge grows! DOI: 10.5281/ zenodo.5995885 20 28 Nov 2025 Total PCL Entries 566,625 Rank 1 795 (81.4 %) Rank 1-2 914 (93.6 %) Rank 1-5 961 (98.4 %) Failures 9 (0.9 %) Total Evaluated 977 (100 %) File Size 257,713 >81 % Ranked first >93 % Ranked second => High throughput identification (quickly!) Schymanski et al. (2021) DOI: 10.1186/s13321-021-00489-0; Elapavalore et al. (2025) DOI: 10.1021/acs.estlett.4c01003 for Exposomics – Website 21 http://pubchemlite.lcsb.uni.lu/ caffeine Database: for Exposomics 22 https://pubchemlite.lcsb.uni.lu/e/compound/2519 caffeine Database: for Exposomics 23 https://pubchemlite.lcsb.uni.lu/e/compound/2519 caffeine Database: for Exposomics 24 https://pubchemlite.lcsb.uni.lu/e/compound/2519 caffeine Database: for Exposomics 25 https://pubchemlite.lcsb.uni.lu/e/compound/2519 …and now in 2025: Fluorinated ions are everywhere… Tisler et al. (2025) DOI: 10.1021/acs.est.5c06876 32 Coverage of Content 33 Source: Talavera Andújar & Schymanski, under review, Exposome. https://gitlab.com/uniluxembourg/lcsb/eci/exposomics-plots. Triglycerides Nucleotides EU Pesticides PFOS and related substances Environmental Cheminformatics @ LCSB, Uni.lu FAIR chemical data Open source mass spectral library HRMS NTS TP workflows Slide inspired by B. Talavera Explore chemical space Browse transformations 34 Disease impacts Talavera Andújar et al. (2024). Environment International DOI: 10.1016/j.envint.2024.109151 35 Environmental Factors & Reduced Penetrance in PD Talavera Andújar et al. (2024). Environment International DOI: 10.1016/j.envint.2024.109151 36 Reduced Penetrance: PD, LRRK2 – Multi-omics on Dust Control (n=11) iPD (n=11) PD-/LRRK2+ (n=8) PD+/LRRK2+ (n=11) Control (n=8) iPD (n=3) PD-/LRRK2+ (n=8) PD+/LRRK2+ (n=5) Dust sample collection Serum sample collection Liquid-liquid extraction Bile acids extraction DNA extraction Monophasic extraction DNA sequencing HRMS LC MTBE MeOH+ H 2 O Non-polar metabolites Polar metabolites RP (CSH C18) Q Exactive HF HRMSLC EXPLORIS 240 NextSeq500 (Illumina) HILIC RP (BEH C18) HILIC Talavera Andújar et al. (2024). Environment International DOI: 10.1016/j.envint.2024.109151 37 Exposomics Workflows – Best of Many Worlds! Chemical Classification: PD, LRRK2 Penetrance & Dust Talavera Andújar et al. (2024). Environment International DOI: 10.1016/j.envint.2024.109151 38 Is Regrettable Substitution Impacting Neurodegeneration? Talavera Andújar et al. (2024). Environment International DOI: 10.1016/j.envint.2024.109151 39 Control iPD PD-/LRRK2+ PD+/LRRK2+ -2 -1 0 1 2 BPS Normalized peak intensity p=0.0117 p=0.0591 p=0.0620 Emerged as a “safer” alternative to bisphenol A (BPA) Control iPD PD-/LRRK2+ PD+/LRRK2+ -3 -2 -1 0 1 2 3 PFBuS Normalized peak intensity p=0.0184 p=0.0069 p=0.0649 PFBuS is a substitute for perfluorooctanesulfonate (PFOS) 1,003 chemicals Perfluorobutane Sulfonic Acid Bisphenol S Use and manufacturing (549) Associated Disease/Disorder (543) Pathways (331) Hazardous chemical replacements (2) Compound TOC BPS Impacting Mitochondria in Patient-Derived Neurons Talavera Andújar et al. (2024). Environment International DOI: 10.1016/j.envint.2024.109151 40 Environmental Cheminformatics @ LCSB, Uni.lu FAIR chemical data Open source mass spectral library HRMS NTS TP workflows Slide inspired by B. Talavera Explore chemical space Browse transformations 41 Disease impacts FAIR-TPs – Explore TPs Extracted From Literature 48 Mayahi, Palm & Schymanski (in prep.). https://fairtps.lcsb.uni.lu/ FAIR-TPs – How much do we really know about TFA? 49 Mayahi, Palm & Schymanski (in prep.). https://fairtps.lcsb.uni.lu/ 18 known data points in FAIR-TPs https://pubchem.ncbi.nlm.nih.gov/classification/#hid=120 Schymanski et al. (2023) ES&T DOI: 10.1021/acs.est.3c04855 Browsing Dead-End (and other) Predicted TPs 50 https://gcitps.lcsb.uni.lu/ & Palm et al. (2025) Presentation at SETAC Europe, 13 May 2025. DOI: 10.5281/zenodo.15574837 Predicting Dead-end Transformation Products 51 *Test set of 36,273 ZeroPM GCI chemicals <200 Da Source: Emma Palm. Palm et al. (2025) Presentation at SETAC Europe, 13 May 2025. DOI: 10.5281/zenodo.15574837. Number of precursors: 170* Browsing Dead-End (and other) Predicted TPs 52 *Test set of 36,273 ZeroPM GCI chemicals <200 Da Source: Emma Palm. Palm et al. (2025) Presentation at SETAC Europe, 13 May 2025. DOI: 10.5281/zenodo.15574837. Predicting Dead-end Transformation Products 53 Number of precursors: 13* *Test set of 36,273 ZeroPM GCI chemicals <200 Da Source: Emma Palm. Palm et al. (2025) Presentation at SETAC Europe, 13 May 2025. DOI: 10.5281/zenodo.15574837. Predicting Dead-end Transformation Products 54 Number of precursors: 13* *Test set of 36,273 ZeroPM GCI chemicals <200 Da Source: Emma Palm. Palm et al. (2025) Presentation at SETAC Europe, 13 May 2025. DOI: 10.5281/zenodo.15574837. Environmental Cheminformatics @ LCSB, Uni.lu FAIR chemical data Open source mass spectral library HRMS NTS TP workflows Slide inspired by B. Talavera Explore chemical space Browse transformations 55 Disease impacts Email: emma.schymans[email protected] in:emma-schymanski / @[email protected] https://wwwen.uni.lu/lcsb/research/environmental_ cheminformatics/ https://gitlab.com/uniluxembourg/lcsb/eci/ https://pubchemlite.lcsb.uni.lu/ Merci/Danke schön/Thank you! H2020: 101036756 56 Analytical Frontiers Computational Tools TPs & PMTs NTS & Hazard Assessment NTS & Managing Chemicals Please join us in Ascona for Nontarget2026! When: April 12-17, 2026 Abstract submission: Closing soon - get in quick! More details: https://www.eawag.ch/nontarget2026