Multi-target drug repositioning by bipartite block-wise sparse multi-task learning.

Journal: BMC systems biology
Published Date:

Abstract

BACKGROUND: Finding potential drug targets is a crucial step in drug discovery and development. Recently, resources such as the Library of Integrated Network-Based Cellular Signatures (LINCS) L1000 database provide gene expression profiles induced by various chemical and genetic perturbations and thereby make it possible to analyze the relationship between compounds and gene targets at a genome-wide scale. Current approaches for comparing the expression profiles are based on pairwise connectivity mapping analysis. However, this method makes the simple assumption that the effect of a drug treatment is similar to knocking down its single target gene. Since many compounds can bind multiple targets, the pairwise mapping ignores the combined effects of multiple targets, and therefore fails to detect many potential targets of the compounds.

Authors

  • Limin Li
  • Xiao He
    Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland. xiao.he@bsse.ethz.ch.
  • Karsten Borgwardt
    Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.