Project summary: In the human body, the small molecule chemical space originates from 1) the exposome( natural or synthetic exogenous compounds) and the metabolome (functional readout of metabolic pathways of host and commensal microbiota genomes). Studying this chemical space has provided new insights into the initiation and progression of cancer, neurological, cardiovascular and respiratory diseases and biomarkers for exposures to industrial chemicals, nutrients, drugs and bioactive internal molecules. Targeted biomonitoring and untargeted chemical analysis assays generate core datasets for exposomics projects to study the chemical space and its impact on human health. Inter-chemical correlations are ubiquitously observed in these core datasets. However, interpretation of these correlations has been limited to metabolic pathway and reaction contexts which do not cover the origin, source, transformation and interaction among exposome chemicals. We propose to develop the Exposome Correlation and Interpretation Database (ECID), a new biomedical knowledgebase that will systematically catalogue and curate inter-chemical correlations and their interpretation for the core datasets in exposomics. ECID will have three main informatics resources 1) Chemical Correlation Database (CCDB), a curated, trustworthy, and FAIR compliance database of inter- chemical correlations from biomonitoring and untargeted chemical analysis assays (aim1). In the prototype version, 56 datasets have been included and by end of the project, over 250 datasets (human-only) will be covered by the CCDB. We will curate the inter-chemical correlations that are observed across multiple studies. 2) Exposome Data Interpretation Resource (EDIR), an integrated database of structural and functional relationships among chemicals (aim 2). Aim 2 will utilize text mining, cheminformatics, database fusion, ontologies and chemical network mapping methods to create an atlas of functional and structural relationships among exposome chemicals. EDIR will be used for annotating curated inter-chemical correlations with plausible interpretations. and 3) Exposome WorkSpace, an online space to explore the CCDB and EDIR information and to interpret user-provided datasets (aim 3). We will re-engineer the established data exploration and analytics methods to provide an integrated, focused and relevant framework for exploring inter- chemical correlations in core exposomics datasets. ECID portal will provide self-guided tutorials and online data exploration tools for the exposomics and metabolomics researchers. ECID will leverage and complement the HHEAR program's data center, targeted and untargeted laboratory components at the Mount Sinai Exposomics Hub. We will utilize HHEAR studies (post-embargo) as validation studies to showcase the application of ECID in exposome research. ECID will make significant contributions towards expanding our understanding about small molecules chemical space within the human body by revealing exposure chemical's health effects, new metabolic and xenobiotic transformation pathways, and exposure groups.

Project narrative: Inter-chemical correlations in exposomics core datasets enable linking the exposome chemical space with human health. The Exposome Correlation and Interpretation Database (ECID), a new biomedical knowledgebase will provide curated inter-chemical correlations and online portals to explore, analyze and interpret them in exposomics datasets.