Building an Adverse Outcome Pathway network for COVID-19

Area of Science:

• Toxicology and Pharmacology
• Computational Biology
• Infectious Diseases

Background:

• The COVID-19 pandemic generated extensive data on disease pathogenesis.
• Organizing this vast knowledge is crucial for understanding COVID-19 pathology.
• The Adverse Outcome Pathway (AOP) framework offers a structured approach to knowledge organization.

Purpose of the Study:

• To systematically organize published scientific literature on COVID-19 pathology using the AOP framework.
• To computationally derive and refine an AOP network for COVID-19.
• To identify challenges and propose recommendations for building AOP networks for viral diseases.

Main Methods:

• The CIAO consortium gathered and organized literature on COVID-19 pathology between April 2020 and February 2023.
• Identified 24 relevant pathways with essential key events (KEs) leading to 19 adverse outcomes.
• Selected 17 AOPs based on quality criteria to computationally derive an AOP network, followed by manual refinement.

Main Results:

• The derived AOP network visualized complex interactions of KEs leading to COVID-19 outcomes.
• Confirmed the central role of the inflammatory response in COVID-19 pathogenesis.
• Highlighted the importance of tissue specificity, terminology harmonization, and FAIR principles for AOP network development.

Conclusions:

• AOP network construction requires addressing tissue specificity and harmonizing terminology.
• The FAIR principles are essential for improving AOP findability, accessibility, interoperability, and reusability.
• Adaptations to the AOP framework are needed to describe SARS-CoV-2 specific KEs and differentiate physiological from pathological inflammation.