Defining clinical outcome pathways.

Journal: Drug discovery today
Published Date: Feb 16, 2022

Abstract

Here, we propose a broad concept of 'Clinical Outcome Pathways' (COPs), which are defined as a series of key molecular and cellular events that underlie therapeutic effects of drug molecules. We formalize COPs as a chain of the following events: molecular initiating event (MIE) → intermediate event(s) → clinical outcome. We illustrate the concept with COP examples both for primary and alternative (i.e., drug repurposing) therapeutic applications. We also describe the elucidation of COPs for several drugs of interest using the publicly accessible Reasoning Over Biomedical Objects linked in Knowledge-Oriented Pathways (ROBOKOP) biomedical knowledge graph-mining tool. We propose that broader use of COP uncovered with the help of biomedical knowledge graph mining will likely accelerate drug discovery and repurposing efforts.

Authors

  • Daniel Korn
    Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Andrew J Thieme
    UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
  • Vinicius M Alves
    Laboratory for Molecular Modeling, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
  • Michael Yeakey
    Massachusetts College of Pharmacy and Health Sciences, Boston, MA, USA.
  • Joyce V V B Borba
    LabMol-Laboratory for Molecular Modeling and Drug Design, Faculdade de Farmácia, Universidade Federal de Goiás-UFG, Goiânia, GO, Brazil.
  • Stephen J Capuzzi
    UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599.
  • Karamarie Fecho
    Renaissance Computing Institute , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina 27517 , United States.
  • Chris Bizon
    Renaissance Computing Institute , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina 27517 , United States.
  • Stephen W Edwards
    RTI International, Research Triangle Park, NC, USA.
  • Rada Chirkova
    Department of Computer Science, North Carolina State University, Raleigh, NC 27695-8206, USA.
  • Christine M Colvis
    National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
  • Noel T Southall
    Department of Computer Science, North Carolina State University, Raleigh, NC, USA.
  • Christopher P Austin
    National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, United States.
  • Eugene N Muratov
    Laboratory for Molecular Modeling, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, United States of America.
  • Alexander Tropsha
    Laboratory for Molecular Modeling, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.

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