FAIR and Open Computational Approaches for 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/ FAIR and Open Computational Approaches for Exposomics Slides available at DOI: 10.5281/zenodo.17732397 Computational Mini Symposium: Defense of Niek de Jonge Wageningen University & Research, 28 November 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 26 Nov. 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 26 Nov. 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 26 Nov. 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 … 133,648 suspects Suspect Screening Target Analysis Numbers updated 26 Nov. 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 122 million 129 million Candidates with high information content Candidates with low information content 1.2 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 for Exposomics 19 http://pubchemlite.lcsb.uni.lu/ caffeine Database: for Exposomics 20 https://pubchemlite.lcsb.uni.lu/e/compound/2519 caffeine Database: for Exposomics 21 https://pubchemlite.lcsb.uni.lu/e/compound/2519 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 Database: for Exposomics 24 https://pubchemlite.lcsb.uni.lu/e/compound/2519 Aurich et al. (2024) ES&T Letters DOI: 10.1021/acs.estlett. 4c00560 caffeine Database: for Exposomics 25 https://pubchemlite.lcsb.uni.lu/e/compound/2519 caffeine is a Dynamic Collection … •… built every week, updated online every month •… re-evaluated with every build for continuous quality control •… growing as knowledge grows! DOI: 10.5281/ zenodo.5995885 32 http://pubchemlite.lcsb.uni.lu/ Variation of Content Over Time (2022-2024) •Variation of content over time Elapavalore et al. (2025) DOI: 10.1021/acs.estlett.4c01003 33 Coverage of Content 34 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 35 Disease impacts Talavera Andújar et al. (2024). Environment International DOI: 10.1016/j.envint.2024.109151 36 Environmental Factors & Reduced Penetrance in PD Talavera Andújar et al. (2024). Environment International DOI: 10.1016/j.envint.2024.109151 37 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 38 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 39 Is Regrettable Substitution Impacting Neurodegeneration? Talavera Andújar et al. (2024). Environment International DOI: 10.1016/j.envint.2024.109151 40 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 41 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 Schymanski et al. (2023) ES&T DOI: 10.1021/acs.est.3c04855 Transforming with BioTransformer http://biotransformer.ca/ Schymanski et al. (2021) DOI: 10.1186/s13321-021-00489-0; Bolton et al (2021) preliminary calculations; Schymanski, Bolton, Cheng, Thiessen, Zhang, Helmus (2021) Transformations in PubChem, DOI: 10.5281/zenodo.5644560 Djoumbou Feunang et al (2019). BioTransformer, JCheminf. DOI: 10.1186/s13321‐018‐0324‐5. 379,199 entries human/env 11 M 2.4 M 1.2 M Combinatorial explosion – more data needed to predict reaction likelihoods humenvhum 36 M 98 M 86 M 3.6 M 11 M 30 M 82 M version 1.0.0; DOI: 10.5281/zenodo.5995886 50 Browsing Dead-End (and other) Predicted TPs 51 https://gcitps.lcsb.uni.lu/ & Palm et al. (2025) Presentation at SETAC Europe, 13 May 2025. DOI: 10.5281/zenodo.15574837 Predicting Dead-end TPs - ZeroPM Global Chemical Inventory Source: Emma Palm. Palm et al. (2025) Presentation at SETAC Europe, 13 May 2025. DOI: 10.5281/zenodo.15574837. 52 Predicting Dead-end Transformation Products 53 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 54 Source: Emma Palm. Palm et al. (2025) Presentation at SETAC Europe, 13 May 2025 . DOI: 10.5281/zenodo.15574837 Predicting Dead-end Transformation Products 55 Source: Emma Palm. Palm et al. (2025) Presentation at SETAC Europe, 13 May 2025 . DOI: 10.5281/zenodo.15574837 Number of precursors: 13 Predicting Dead-end Transformation Products 56 Source: Emma Palm. Palm et al. (2025) Presentation at SETAC Europe, 13 May 2025 . DOI: 10.5281/zenodo.15574837 Number of precursors: 13 FAIR-TPs 57 Mayahi, Palm & Schymanski (in prep.). https://fairtps.lcsb.uni.lu/stats/ & https://fairtps.lcsb.uni.lu/about/