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Summary
This summary is machine-generated.

Networking adverse outcome pathways (AOPs) reveals thousands of new linear AOPs (LAOPs), highlighting the AOP knowledgebase (KB) as a source of emergent toxicological knowledge for risk assessment and management.

Keywords:
AOP networksadverse outcome pathwayemergent knowledgenetwork analysis

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Area of Science:

  • Toxicology
  • Computational Biology
  • Systems Biology

Background:

  • The adverse outcome pathway (AOP) framework organizes toxicological knowledge.
  • The online AOP knowledgebase (KB) is growing in AOPs.
  • Networking AOPs is a novel approach to analyze this growth.

Purpose of the Study:

  • To analyze the growth and structure of the AOP-KB by creating a network of AOPs.
  • To identify emergent linear AOPs (LAOPs) from the network.
  • To understand patterns of AOP emergence and guide future KB development.

Main Methods:

  • Assembled 187 user-defined AOPs from the AOP-KB into a single network.
  • Calculated summary measures of network connectivity and structure.
  • Sequentially added AOPs to investigate emergent LAOP patterns.

Main Results:

  • Networking 187 AOPs generated 9405 unique, previously undescribed LAOPs.
  • Emergence of new LAOPs is driven by borrowing components from existing AOPs.
  • Nonadjacent key event relationships and cycles also contribute to LAOP formation.

Conclusions:

  • The global AOP network offers significant value as a source of emergent toxicological knowledge.
  • Findings aid in understanding emergent information and managing AOP-KB development.
  • The network can be tailored to specific applications for risk assessment and management.