Prediction of non-genotoxic hepatocarcinogenicity using chemical-protein interactions

  • Authors:
  • Chun-Wei Tung

  • Affiliations:
  • School of Pharmacy, Kaohsiung Medical University, Taiwan,Toxicology, Kaohsiung Medical University, Taiwan

  • Venue:
  • PRIB'13 Proceedings of the 8th IAPR international conference on Pattern Recognition in Bioinformatics
  • Year:
  • 2013

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Abstract

The assessment of non-genotoxic hepatocarcinogenicity of chemicals is currently based on 2-year rodent bioassays. It is desirable to develop a fast and effective method to accelerate the identification of potential hepatocarcinogenicity of non-genotoxic chemicals. In this study, a novel method CPI is proposed to predict potential hepatocarcinogenicity of non-genotoxic chemicals. The CPI method is based on chemical-protein interactions and interpretable decision tree classifiers.The interpretable rules generated by the CPI method are analyzed to provide insights into the mechanism and biomarkers of non-genotoxic hepatocarcinogenicity. The CPI method with an independent test accuracy of 86% using only 1 protein biomarker outperforms the state-of-the-art methods of gene expression profile-based toxicogenomics using 90 gene biomarkers. A protein ABCC3 was identified as a potential protein biomarker for further exploration. This study presents the potential application of CPI method for assessing non-genotoxic hepatocarcinogenicity of chemicals.