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

Kazi, Julhash U LU orcid and Pienta, Kenneth J LU (2026) In Medical Oncology 43(6).
Abstract

Despite extensive cataloging of carcinogenic exposures by the International Agency for Research on Cancer (IARC) and pharmacogenomic variation by resources such as PharmVar and CPIC, few platforms unify exposure, metabolic activation and detoxification, DNA damage, and genetic annotation within a single interactive visualization framework. This gap limits systematic evaluation of gene-environment interactions in cancer risk assessment. We developed the Carcino-Genomic Knowledge Graph, ExposoGraph, an interactive knowledge-graph platform for carcinogen metabolism and DNA damage pathways. The reference graph integrates curated data and annotations from IARC, KEGG, PharmVar, CPIC, CTD, and supporting literature/resources. The current... (More)

Despite extensive cataloging of carcinogenic exposures by the International Agency for Research on Cancer (IARC) and pharmacogenomic variation by resources such as PharmVar and CPIC, few platforms unify exposure, metabolic activation and detoxification, DNA damage, and genetic annotation within a single interactive visualization framework. This gap limits systematic evaluation of gene-environment interactions in cancer risk assessment. We developed the Carcino-Genomic Knowledge Graph, ExposoGraph, an interactive knowledge-graph platform for carcinogen metabolism and DNA damage pathways. The reference graph integrates curated data and annotations from IARC, KEGG, PharmVar, CPIC, CTD, and supporting literature/resources. The current reference graph contains 98 nodes across 5 entity types (Carcinogens, Enzymes, Metabolites, DNA Adducts, and Pathways) and 118 edges across 6 relationship types (activates, detoxifies, transports, forms adduct, repairs, and pathway). The first-generation reference graph captures metabolic activation and detoxification pathways for 9 carcinogen classes spanning 15 index carcinogens. It represents 38 enzymes across Phase I activation (n = 14), Phase II conjugation and detoxification (n = 14), Phase III transport (n = 3), and DNA repair (n = 7). Interactive exploration supports carcinogen-class filtering, node- and edge-type filtering, metadata-based search, and detailed hover/detail views with provenance and pharmacogenomic annotations. The androgen branch highlights cross-pathway connectivity by linking androgen metabolism to estrogen quinone formation and DNA adduct generation through CYP19A1-mediated aromatization and downstream catechol estrogen chemistry. In the optional androgen-focused extension, additional receptor, tissue, and variant context further connects this branch to androgen receptor signaling and genotype-specific annotations. ExposoGraph provides a first-generation integrated, interactive framework linking carcinogenic exposures to metabolic fates and genetic modulators. The platform supports hypothesis generation for gene-environment interaction studies and may inform future individualized risk modeling, while remaining a research-use framework rather than a clinically validated risk-assessment tool.

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Please use this url to cite or link to this publication:
author
and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Carcinogens/metabolism, Neoplasms/metabolism, Inactivation, Metabolic, DNA Damage, Activation, Metabolic, Metabolic Networks and Pathways, Gene-Environment Interaction
in
Medical Oncology
volume
43
issue
6
article number
187
publisher
Humana Press
external identifiers
  • pmid:42138795
  • scopus:105039279403
ISSN
1559-131X
DOI
10.1007/s12032-026-03297-4
language
English
LU publication?
yes
additional info
© 2026. The Author(s).
id
c78d1caf-b09f-4508-8ccd-de4fa983ac1b
date added to LUP
2026-05-18 18:42:45
date last changed
2026-07-30 13:41:30
@article{c78d1caf-b09f-4508-8ccd-de4fa983ac1b,
  abstract     = {{<p>Despite extensive cataloging of carcinogenic exposures by the International Agency for Research on Cancer (IARC) and pharmacogenomic variation by resources such as PharmVar and CPIC, few platforms unify exposure, metabolic activation and detoxification, DNA damage, and genetic annotation within a single interactive visualization framework. This gap limits systematic evaluation of gene-environment interactions in cancer risk assessment. We developed the Carcino-Genomic Knowledge Graph, ExposoGraph, an interactive knowledge-graph platform for carcinogen metabolism and DNA damage pathways. The reference graph integrates curated data and annotations from IARC, KEGG, PharmVar, CPIC, CTD, and supporting literature/resources. The current reference graph contains 98 nodes across 5 entity types (Carcinogens, Enzymes, Metabolites, DNA Adducts, and Pathways) and 118 edges across 6 relationship types (activates, detoxifies, transports, forms adduct, repairs, and pathway). The first-generation reference graph captures metabolic activation and detoxification pathways for 9 carcinogen classes spanning 15 index carcinogens. It represents 38 enzymes across Phase I activation (n = 14), Phase II conjugation and detoxification (n = 14), Phase III transport (n = 3), and DNA repair (n = 7). Interactive exploration supports carcinogen-class filtering, node- and edge-type filtering, metadata-based search, and detailed hover/detail views with provenance and pharmacogenomic annotations. The androgen branch highlights cross-pathway connectivity by linking androgen metabolism to estrogen quinone formation and DNA adduct generation through CYP19A1-mediated aromatization and downstream catechol estrogen chemistry. In the optional androgen-focused extension, additional receptor, tissue, and variant context further connects this branch to androgen receptor signaling and genotype-specific annotations. ExposoGraph provides a first-generation integrated, interactive framework linking carcinogenic exposures to metabolic fates and genetic modulators. The platform supports hypothesis generation for gene-environment interaction studies and may inform future individualized risk modeling, while remaining a research-use framework rather than a clinically validated risk-assessment tool.</p>}},
  author       = {{Kazi, Julhash U and Pienta, Kenneth J}},
  issn         = {{1559-131X}},
  keywords     = {{Humans; Carcinogens/metabolism; Neoplasms/metabolism; Inactivation, Metabolic; DNA Damage; Activation, Metabolic; Metabolic Networks and Pathways; Gene-Environment Interaction}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{6}},
  publisher    = {{Humana Press}},
  series       = {{Medical Oncology}},
  title        = {{ExposoGraph : An Interactive Platform for Carcinogen Bioactivation and Detoxification Pathway Visualization}},
  url          = {{http://dx.doi.org/10.1007/s12032-026-03297-4}},
  doi          = {{10.1007/s12032-026-03297-4}},
  volume       = {{43}},
  year         = {{2026}},
}