A Network Toxicology Approach for Mechanistic Modelling of Nanomaterial Hazard and Adverse Outcomes

Autor: Giusy del Giudice, Angela Serra, Alisa Pavel, Marcella Torres Maia, Laura Aliisa Saarimäki, Michele Fratello, Antonio Federico, Harri Alenius, Bengt Fadeel, Dario Greco
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Advanced Science, Vol 11, Iss 32, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2198-3844
DOI: 10.1002/advs.202400389
Popis: Abstract Hazard assessment is the first step in evaluating the potential adverse effects of chemicals. Traditionally, toxicological assessment has focused on the exposure, overlooking the impact of the exposed system on the observed toxicity. However, systems toxicology emphasizes how system properties significantly contribute to the observed response. Hence, systems theory states that interactions store more information than individual elements, leading to the adoption of network based models to represent complex systems in many fields of life sciences. Here, they develop a network‐based approach to characterize toxicological responses in the context of a biological system, inferring biological system specific networks. They directly link molecular alterations to the adverse outcome pathway (AOP) framework, establishing direct connections between omics data and toxicologically relevant phenotypic events. They apply this framework to a dataset including 31 engineered nanomaterials with different physicochemical properties in two different in vitro and one in vivo models and demonstrate how the biological system is the driving force of the observed response. This work highlights the potential of network‐based methods to significantly improve their understanding of toxicological mechanisms from a systems biology perspective and provides relevant considerations and future data‐driven approaches for the hazard assessment of nanomaterials and other advanced materials.
Databáze: Directory of Open Access Journals
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