Beyond Traditional Toxicology: The Power of Toxicogenomics for Early Risk Assessment

In the evolving landscape of chemical and pharmaceutical development, traditional methods of toxicology, which are often heavily reliant on animal testing, are facing increasing scrutiny due to ethical concerns, cost, and time constraints. Enter toxicogenomics, a revolutionary field that is transforming how we assess the safety of compounds. At Edelweiss Connect, through our SaferWorldByDesign initiative, we're at the forefront of leveraging this powerful science for early, efficient, and ethical risk assessment.

What is Toxicogenomics?

Toxicogenomics combines toxicology with genomics, transcriptomics, proteomics, and metabolomics. It investigates how genes and their expression are affected by exposure to toxic substances. By analyzing these molecular changes, we can gain an unprecedented understanding of a compound's potential to cause harm, often long before visible effects emerge. This detailed molecular insight allows for a proactive and more precise approach to risk assessment.

Shifting Paradigms: From Animal Studies to Molecular Insights

For decades, determining the Point of Departure (PoD) – the lowest dose at which an adverse effect is observed – has been critical for risk assessment. Traditionally, this involved extensive in vivo studies. However, toxicogenomics offers a powerful alternative. By analyzing gene expression changes in in vitro models, we can identify molecular perturbations that signal potential toxicity at very early stages of development. This allows for the derivation of PoDs without the need for animal experiments, aligning with the 3Rs (Replace, Reduce, Refine) principles of animal welfare.

Edelweiss Connect and the in3 Project: A Case Study in Innovation

Our commitment to this innovative approach is exemplified by our significant role in pioneering European projects, such as in3 (integrated in vitro & in silico tools). The in3 project, an EU's EU-funded initiative, aims to synergistically develop and utilize in vitro and in silico tools for human chemical and nanomaterial safety assessment across various organs, including the kidney, liver, brain, lung, and blood-brain barrier.

Within in3, Edelweiss Connect has been instrumental in developing bioinformatics workflows for predicting chronic kidney disease based on IPS cell data, leveraging transcriptomics data from databases like DrugMatrix. This work involves:

• Collecting and harmonizing vast amounts of heterogeneous data from in vitro experiments and public sources.

• Mining and interpreting this data to elucidate modes of action and link them to Adverse Outcome Pathways (AOPs).

• Discovering biomarkers to identify key events (KEs) within AOPs, making them more understandable, enriched, and specific.

  
  

The MSCA-ITN in3 project focused on human iPSC-derived tissues (brain, lung, liver, kidney) to develop in vitro and in silico approaches for human chemical and nanomaterial safety. This involved generating in vitro transcriptomic data, identifying differentially expressed genes (DEGs), and enriching pathways using these findings. This rigorous data-driven approach allowed researchers to identify potential biomarkers for nephrotoxicity and propose new key events within the AOP network.

Your One-Stop-Shop for Next-Generation Toxicology

At Edelweiss Connect, we act as an integrator of these highly specialized services within the SaferWorldByDesign platform. This means you can consider us a one-stop shop for your toxicology needs. From designing suitable in vitro experiments to executing them with world-class partners, performing transcriptomic analysis (RNA sequencing), and expertly collecting, processing, and analyzing data – we provide a seamless, end-to-end solution. Our expertise in data management, analysis, and modeling, combined with our strong networking community, ensures unparalleled rigor and insight.

By embracing toxicogenomics, we're not just moving beyond traditional methods; we're building a safer world by design, providing our clients with the precise, mechanistic understanding needed to de-risk their compounds and accelerate innovation.