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

Giusy del Giudice, Angela Serra, Alisa Pavel, Marcella Torres Maia, Laura Aliisa Saarimäki, Michele Fratello, Antonio Federico, Harri Alenius, Bengt Fadeel, Dario Greco

Research output: Contribution to journalArticleScientificpeer-review

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.

Original languageEnglish
Article number2400389
JournalAdvanced Science
Volume11
Issue number32
Number of pages15
ISSN2198-3844
DOIs
Publication statusPublished - 2024
MoE publication typeA1 Journal article-refereed

Fields of Science

  • adverse outcome pathways
  • complex systems
  • engineered nanomaterials
  • network theory
  • systems toxicology
  • toxicogenomics
  • 221 Nano-technology
  • 317 Pharmacy

Cite this