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A Classification Model to Identify Direct-Acting Mutagenic Polycyclic Aromatic Hydrocarbon Transformation Products.

Publication ,  Journal Article
Sleight, TW; Sexton, CN; Mpourmpakis, G; Gilbertson, LM; Ng, CA
Published in: Chemical research in toxicology
November 2021

Polycyclic aromatic hydrocarbons (PAHs) are a complex group of environmental contaminants, many having long environmental half-lives. As these compounds degrade, the changes in their structure can result in a substantial increase in mutagenicity compared to the parent compound. Over time, each individual PAH can potentially degrade into several thousand unique transformation products, creating a complex, constantly evolving set of intermediates. Microbial degradation is the primary mechanism of their transformation and ultimate removal from the environment, and this process can result in mutagenic activation similar to the metabolic activation that can occur in multicellular organisms. The diversity of the potential intermediate structures in PAH-contaminated environments renders hazard assessment difficult for both remediation professionals and regulators. A mixture of structural and energetic descriptors has proven effective in existing studies for classifying which PAH transformation products will be mutagenic. However, most existing studies of environmental PAH mutagens primarily focus on nitrogenated derivatives, which are prevalent in the atmosphere and not as relevant in soil. Additionally, PAH products commonly found in the environment can range from as large as five rings to as small as a single ring, requiring a broadly inclusive methodology to comprehensively evaluate mutagenic potential. We developed a combination of supervised and unsupervised machine learning methods to predict environmentally induced PAH mutagenicity with improved performance over currently available tools. K-means clustering with principal component analysis allows us to identify molecular clusters that we hypothesize to have similar mechanisms of action. Recursive feature elimination identifies the most influential descriptors. The cluster-specific regression outperforms available classifiers in predicting direct-acting mutagens resulting from the microbial biodegradation of PAHs and provides direction for future studies evaluating the environmental hazards resulting from PAH biodegradation.

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Published In

Chemical research in toxicology

DOI

EISSN

1520-5010

ISSN

0893-228X

Publication Date

November 2021

Volume

34

Issue

11

Start / End Page

2273 / 2286

Related Subject Headings

  • Toxicology
  • Principal Component Analysis
  • Polycyclic Aromatic Hydrocarbons
  • Mutagenicity Tests
  • Mutagenesis
  • Molecular Structure
  • Logistic Models
  • Databases, Factual
  • 3405 Organic chemistry
  • 3404 Medicinal and biomolecular chemistry
 

Citation

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Sleight, T. W., Sexton, C. N., Mpourmpakis, G., Gilbertson, L. M., & Ng, C. A. (2021). A Classification Model to Identify Direct-Acting Mutagenic Polycyclic Aromatic Hydrocarbon Transformation Products. Chemical Research in Toxicology, 34(11), 2273–2286. https://doi.org/10.1021/acs.chemrestox.1c00187
Sleight, Trevor W., Caitlin N. Sexton, Giannis Mpourmpakis, Leanne M. Gilbertson, and Carla A. Ng. “A Classification Model to Identify Direct-Acting Mutagenic Polycyclic Aromatic Hydrocarbon Transformation Products.Chemical Research in Toxicology 34, no. 11 (November 2021): 2273–86. https://doi.org/10.1021/acs.chemrestox.1c00187.
Sleight TW, Sexton CN, Mpourmpakis G, Gilbertson LM, Ng CA. A Classification Model to Identify Direct-Acting Mutagenic Polycyclic Aromatic Hydrocarbon Transformation Products. Chemical research in toxicology. 2021 Nov;34(11):2273–86.
Sleight, Trevor W., et al. “A Classification Model to Identify Direct-Acting Mutagenic Polycyclic Aromatic Hydrocarbon Transformation Products.Chemical Research in Toxicology, vol. 34, no. 11, Nov. 2021, pp. 2273–86. Epmc, doi:10.1021/acs.chemrestox.1c00187.
Sleight TW, Sexton CN, Mpourmpakis G, Gilbertson LM, Ng CA. A Classification Model to Identify Direct-Acting Mutagenic Polycyclic Aromatic Hydrocarbon Transformation Products. Chemical research in toxicology. 2021 Nov;34(11):2273–2286.
Journal cover image

Published In

Chemical research in toxicology

DOI

EISSN

1520-5010

ISSN

0893-228X

Publication Date

November 2021

Volume

34

Issue

11

Start / End Page

2273 / 2286

Related Subject Headings

  • Toxicology
  • Principal Component Analysis
  • Polycyclic Aromatic Hydrocarbons
  • Mutagenicity Tests
  • Mutagenesis
  • Molecular Structure
  • Logistic Models
  • Databases, Factual
  • 3405 Organic chemistry
  • 3404 Medicinal and biomolecular chemistry