Overview

Important

Welcome to the homepage of the AOP Project!

The AOP Project was independently developed by Shakira Agata under supervision of Marvin Martens to investigate how inflammatory stress response pathways can be modelled in the AOP framework to facilitate transcriptomics integration in chemical risk assessment. Through the execution of 500 documented SCRUM sprints, 11 Jupyter Notebooks were designed as part of the two-tiered approach described in the thesis. The software is structured around two key objectives which were assigned their own respective Jupyter Notebooks to maintain structure and overview. This documentation provides a complete overview and guideline for the use of the two-tiered approach with presence of metadata to ensure reproducibility.

📥 Step 1: Download the Notebooks

The developed Jupyter Notebooks can be downloaded from the GitHub repository. The Notebooks were designed to be run in chronological order, as many rely on outputs from previous steps. In the folder: ‘Inputfiles-demonstration’, users can find the input and output generated files that were used in the Jupyter Notebooks as baseline. The Jupyter Notebooks can be subdivided into:

  • Jupyter Notebooks 1–3: focused on the construction and enrichment of a human inflammatory stress response AOP network.
  • Jupyter Notebooks 4–11: focused on the integration of transcriptomics data into the enriched AOP network via dataset mapping, Key Event (KE) enrichment analysis and benchmarking with Overrepresentation analysis (ORA).

🛠️ Step 2: Getting Started

  1. Open the Jupyter Notebooks
    Navigate to the .ipynb files and launch it in JupyterLab.

  2. Run the cells sequentially
    Use Shift + Enter to execute each cell in order.

  3. Modify/adapt the cells
    Feel free to experiment and tailor the code to your own personal research interest.

Societal and scientific relevancy of the AOP Project
Chemical exposure forms a public health crisis by being responsible for one fourth of the global disease burden. In recent years, the link between chemical exposure and human diseases has been increasingly emphasized as chemical exposure forms an environmental risk factor for multiple diseases including cancer, neuropsychiatric disorders, respiratory diseases, congenital anomalies and kidney diseases. Despite these concerning findings, civilians continue to be exposed to chemicals as chemicals are deeply integrated into the societal infrastructure based on its widespread presence in air, water, food and consumer products. While chemical risk assessments are intended to protect us and the environment from these health concerns, they are clearly proving to be inadequate. The reason for this is that chemical risk assessments rely on the results from animal toxicology tests which have been shown to have poor human translability. This has stimulated the development of next-generation risk assessment methods such as adverse outcome pathways (AOPs) which provide an animal-free risk assessment methods. AOPs describe the biological processes that are activated by chemical exposure in the human body, acting as road maps that explain both the risk and the adverse health outcomes caused by chemical exposure. Recent research has been focused on the incorporation of inflammatory stress response pathways and use of transcriptomics in the AOP framework based on the predictive power that cell stress responses hold in toxicological outcomes and the mechanistic insights that are provided. These incentives struggled with a lack of standardisation and integration which encouraged the development of the AOP project.