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How to easily create, manage and share adverse outcome pathways to accelerate drug discovery programs

Scientists working in drug discovery are all too aware that toxicity testing is critical for drug development. Yet many lack the ideal software to study drug toxicity and waste time juggling multiple tools. New interactive and automated analytical software tools could revolutionize drug toxicity testing.

A common method to study and document drug toxicity is the use of adverse outcome pathways (AOPs), but until now there has been no available software to easily create, share and manage them. Toxicity researchers resort to underpowered and hard-to-use open-source or homebrew software tools, or even curate them by hand as drawings and tables in PowerPoint and Excel. This creates unnecessary work and hampers our ability to produce AOPs that adequately support drug development.

What makes AOPs powerful for studying toxicity?

AOPs demonstrate sequential, causally linked molecular and cellular events that produce a toxic effect when an organism is exposed to a substance (1). AOPs help us create models of biological interactions and toxicity mechanisms that describe how exposure to a substance might cause illness or injury. They suggest cell- or biochemical-based tests for pathway elements that could be used to develop testing strategies for targeted toxicity. We can use AOPs to identify and characterize the mechanisms of toxicity (2), helping to save time and costs in downstream drug testing and validation.

What are the requirements for robust AOP software?

The ideal AOP software lets us easily explore molecular interactions based on causal mechanistic details powered by underlying content. It should include interactive diagrams to visualize these interactions and enable secure sharing, as well as controlled vocabularies.

QIAGEN Ingenuity Pathway Analysis (IPA) offers these optimal AOP capabilities and is a game changer for drug development. Using the new IPA AOP feature, we can build AOPs, connect important events and concepts, and then label them systematically with the correct AOP nomenclature, as shown below.


Figure 1. Example of an AOP in QIAGEN IPA.

Simply start with a molecular initiating event (MIE) and use IPA to pinpoint the event in the diagram, then add other events and outcomes using IPA’s controlled vocabulary. If we want to delve deeper, we can automatically score gene expression and other analyses against the AOPs. What’s more, we can easily and securely share and maintain these AOPs within our organization.

Toxicity testing programs shouldn’t be a bottleneck in drug screening. Using IPA, we can now easily ramp up a strategy for drug toxicity testing with AOPs. Explore more about QIAGEN IPA and request a consultation to ask about adding AOP capabilities to your IPA license.

References:

  1. The Organization for Economic Co-operation and Development (OECD) https://www.oecd.org/chemicalsafety/testing/adverse-outcome-pathways-molecular-screening-and-toxicogenomics.htm Accessed May 25, 2022.
  2. National Toxicology Program at the U.S. Department of Health and Human Services https://ntp.niehs.nih.gov/whatwestudy/niceatm/comptox/ct-aop/aop.html Accessed May 25, 2022.