dAta-dRiven integrated approaches to CHemIcal safety assessMEnt and Drug dEvelopment

Introduction

Traditional in vivo tests are hampering the development of new, safe, and effective chemicals and drugs. If on one hand we need to ensure that dangerous chemicals do not emerge, on the other, we also need to promote rapid and sustainable innovation to successfully overcome the modern challenges of humankind.

Toxicogenomics and AOP

Toxicogenomics aims at clarifying the mechanism of action (MOA) of chemicals by using omics assays. The Adverse Outcome Pathways (AOP) concept is also emerging to contextualize toxicogenomics-derived MOA.

Current Challenges

Efforts are ongoing to anchor AOPs to molecular assays, but systematic embedding of AOP-derived in vitro tests and Integrated Approaches to Testing and Assessment (IATA) are still unestablished. At the same time, toxicogenomics-based evidence still struggles to gain regulatory acceptance.

Proposed Strategy

I aim to implement an integrated strategy based on state-of-the-art big data science, artificial intelligence (AI), toxicogenomics, molecular assays, and cell technology via a novel Knowledge Graph approach.

Development of the Toxicology Knowledge Graph (TKG)

I will do so by developing the Toxicology Knowledge Graph (TKG), an innovative data platform where the currently fragmented knowledge in the field is going to be curated and integrated.

AI Learning Platform

The TKG will serve as a learning platform for artificial intelligence (AI) algorithms, which will be used to:

1. Find new characteristics of chemicals/drugs;
2. Infer associations between exposures and diseases;
3. Select the most relevant cell lines to study specific phenotypes/chemical classes;
4. Find the best genes to be used as reporters for specific AOPs;
5. Define the applicability domain of computational, experimental, and IATA models.

High-Throughput Molecular Assays

I will also establish and validate regulatory-relevant high-throughput molecular assays to investigate the point of departure (PoD) of exposures.

Project Impact

The ARCHIMEDES project will shift the paradigm of chemical and drug development, facilitating the emergence of new, smarter, greener, and more sustainable chemicals, drugs, and materials.