ExposoGraph: An Interactive Platform for Carcinogen Bioactivation and Detoxification Pathway Visualization

Area of Science:

• Bioinformatics
• Genomics
• Toxicology

Background:

• Limited platforms unify carcinogenic exposures, metabolic activation/detoxification, DNA damage, and genetic annotations.
• This gap hinders systematic evaluation of gene-environment interactions in cancer risk assessment.

Purpose of the Study:

• To develop ExposoGraph, an interactive knowledge-graph platform for visualizing carcinogen metabolism and DNA damage pathways.
• To integrate data from IARC, KEGG, PharmVar, CPIC, and CTD for a comprehensive reference graph.

Main Methods:

• Developed an interactive knowledge graph integrating data on carcinogens, enzymes, metabolites, DNA adducts, and pathways.
• The graph includes 98 nodes and 118 edges representing metabolic and DNA damage processes.
• Implemented interactive features for filtering, searching, and detailed views with provenance and pharmacogenomic annotations.

Main Results:

• The reference graph captures metabolic activation and detoxification pathways for 9 carcinogen classes and 15 index carcinogens.
• It represents 38 enzymes across Phase I, II, and III metabolism, and DNA repair.
• The androgen branch demonstrates cross-pathway connectivity, linking androgen metabolism to estrogen quinone formation and DNA adducts via CYP19A1.

Conclusions:

• ExposoGraph provides an integrated framework linking carcinogenic exposures to metabolic fates and genetic modulators.
• The platform facilitates hypothesis generation for gene-environment interaction studies.
• It serves as a research tool to inform future individualized cancer risk modeling.