Predicting drug resistance related to ABC transporters using unsupervised Consensus Self-Organizing Maps

Sci Rep. 2018 May 1;8(1):6803. doi: 10.1038/s41598-018-25235-9.

Abstract

ATP binding cassette (ABC) transporters play a pivotal role in drug elimination, particularly on several types of cancer in which these proteins are overexpressed. Due to their promiscuous ligand recognition, building computational models for substrate classification is quite challenging. This study evaluates the use of modified Self-Organizing Maps (SOM) for predicting drug resistance associated with P-gp, MPR1 and BCRP activity. Herein, we present a novel multi-labelled unsupervised classification model which combines a new clustering algorithm with SOM. It significantly improves the accuracy of substrates classification, catching up with traditional supervised machine learning algorithms. Results can be applied to predict the pharmacological profile of new drug candidates during the drug development process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / antagonists & inhibitors
  • ATP Binding Cassette Transporter, Subfamily B / chemistry
  • ATP Binding Cassette Transporter, Subfamily B / genetics*
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / antagonists & inhibitors
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / chemistry
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics*
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism
  • Algorithms
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cluster Analysis
  • Databases, Factual
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression
  • Humans
  • Ligands
  • Models, Statistical*
  • Multidrug Resistance-Associated Proteins / antagonists & inhibitors
  • Multidrug Resistance-Associated Proteins / chemistry
  • Multidrug Resistance-Associated Proteins / genetics*
  • Multidrug Resistance-Associated Proteins / metabolism
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Substrate Specificity

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Antineoplastic Agents
  • Ligands
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • multidrug resistance-associated protein 1