Defining clinical outcome pathways

Area of Science:

• Pharmacology
• Systems Biology
• Computational Biology

Background:

• Therapeutic effects of drugs are driven by a series of molecular and cellular events.
• Understanding these event chains is crucial for drug discovery and development.
• Current methods may not fully capture the complexity of drug-induced biological changes.

Purpose of the Study:

• To introduce and define the concept of Clinical Outcome Pathways (COPs).
• To formalize COPs as a sequence of molecular initiating event (MIE), intermediate events, and clinical outcome.
• To demonstrate the utility of COPs in drug discovery and repurposing using a knowledge graph-mining tool.

Main Methods:

• Conceptualization of Clinical Outcome Pathways (COPs).
• Formalization of COP structure: MIE → intermediate event(s) → clinical outcome.
• Application of the Reasoning Over Biomedical Objects linked in Knowledge-Oriented Pathways (ROBOKOP) tool for COP elucidation.

Main Results:

• Defined COPs as a structured sequence of biological events.
• Illustrated COP concept with examples for primary and repurposed drug applications.
• Successfully elucidated COPs for selected drugs using the ROBOKOP knowledge graph-mining tool.

Conclusions:

• Clinical Outcome Pathways provide a framework to understand drug mechanisms.
• Biomedical knowledge graph mining, particularly with tools like ROBOKOP, aids in COP discovery.
• Broader adoption of COP elucidation can accelerate drug discovery and repurposing efforts.