Predicting the Absorption Potential of Chemical Compounds Through a Deep Learning Approach

IEEE/ACM Trans Comput Biol Bioinform. 2018 Mar-Apr;15(2):432-440. doi: 10.1109/TCBB.2016.2535233. Epub 2016 Feb 26.

Abstract

The human colorectal carcinoma cell line (Caco-2) is a commonly used in-vitro test that predicts the absorption potential of orally administered drugs. In-silico prediction methods, based on the Caco-2 assay data, may increase the effectiveness of the high-throughput screening of new drug candidates. However, previously developed in-silico models that predict the Caco-2 cellular permeability of chemical compounds use handcrafted features that may be dataset-specific and induce over-fitting problems. Deep Neural Network (DNN) generates high-level features based on non-linear transformations for raw features, which provides high discriminant power and, therefore, creates a good generalized model. We present a DNN-based binary Caco-2 permeability classifier. Our model was constructed based on 663 chemical compounds with in-vitro Caco-2 apparent permeability data. Two hundred nine molecular descriptors are used for generating the high-level features during DNN model generation. Dropout regularization is applied to solve the over-fitting problem and the non-linear activation. The Rectified Linear Unit (ReLU) is adopted to reduce the vanishing gradient problem. The results demonstrate that the high-level features generated by the DNN are more robust than handcrafted features for predicting the cellular permeability of structurally diverse chemical compounds in Caco-2 cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption, Physicochemical / drug effects*
  • Caco-2 Cells
  • Cell Membrane Permeability / drug effects
  • Computational Biology
  • Computer Simulation
  • Deep Learning*
  • Drug Evaluation, Preclinical
  • Humans
  • Models, Statistical*
  • Pharmaceutical Preparations / metabolism*

Substances

  • Pharmaceutical Preparations