Learning to predict the sites of metabolism and metabolic endpoints

  • Author / Creator
    Shi, Zheng
  • When you ingest anything (e.g., food or medicine), your body will break down (metabolize) the compound's molecules; this process clearly affects the safety and the effectiveness of the compound. This breakdown is facilitated by certain proteins that catalyze this process. Thus it is important to predict whether a compound will be catalyzed by a particular protein, how it will be metabolized and what compounds will result from the process. This thesis presents the framework and models for software systems dealing with three subtasks. The substrate predictor will learn to predict whether a given molecule will be catalyzed by a specific enzyme. Here we focus on the cytochrome P450 (CYP) proteins, which catalyze 90% of the drugs currently on the market. Each catalysis process involves at least one "site of metabolism" (SOM), which is the location of a single atom within the compound, where the reaction happens. We learned one SOM predictor for each of the 9 enzymes, that predicts which site(s) of the compound will be modified This SOM predictor involves a novel "ranking and classification" framework, and works with simple-to-compute features. Finally, we present a simple way to generate the metabolic endpoints, given the enzyme and predicted SOMs. The empirical results on small datasets show our overall system, including substrate predictor and SOM predictor, performs quite well and is superior to state-of-art systems, in terms of computational efficiency and/or accuracy.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Department of Computing Science
  • Supervisor / co-supervisor and their department(s)
    • Russ, Greiner (Computing Science)
  • Examining committee members and their departments
    • David Wishart (Computing Science)
    • Guohui Lin (Computing Science)