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Iskalni niz: "avtor" (Colette vom Berg) .

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1.
Systems toxicology approach for assessing developmental neurotoxicity in Larval zebrafish
Roman Li, Marja Talikka, Vincenzo Belcastro, Colette vom Berg, Florian Martin, Manuel C. Peitsch, Julia Hoeng, Anže Županič, 2021, izvirni znanstveni članek

Povzetek: Adverse outcomes that result from chemical toxicity are rarely caused by dysregulation of individual proteins; rather, they are often caused by system-level perturbations in networks of molecular events. To fully understand the mechanisms of toxicity, it is necessary to recognize the interactions of molecules, pathways, and biological processes within these networks. The developing brain is a prime example of an extremely complex network, which makes developmental neurotoxicity one of the most challenging areas in toxicology. We have developed a systems toxicology method that uses a computable biological network to represent molecular interactions in the developing brain of zebrafish larvae. The network is curated from scientific literature and describes interactions between biological processes, signaling pathways, and adverse outcomes associated with neurotoxicity. This allows us to identify important signaling hubs, pathway interactions, and emergent adverse outcomes, providing a more complete understanding of neurotoxicity. Here, we describe the construction of a zebrafish developmental neurotoxicity network and its validation by integration with publicly available neurotoxicity-related transcriptomic datasets. Our network analysis identified consistent regulation of tumor suppressors p53 and retinoblastoma 1 (Rb1) as well as the oncogene Krüppel-like factor (Klf8) in response to chemically induced developmental neurotoxicity. The developed network can be used to interpret transcriptomic data in a neurotoxicological context.
Objavljeno v DiRROS: 19.07.2024; Ogledov: 190; Prenosov: 151
.pdf Celotno besedilo (3,16 MB)
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2.
From causal networks to adverse outcome pathways : a developmental neurotoxicity case study
Živa Ramšak, Vid Modic, Roman A. Li, Colette vom Berg, Anže Županič, 2022, izvirni znanstveni članek

Povzetek: The last decade has seen the adverse outcome pathways (AOP) framework become one of the most powerful tools in chemical risk assessment, but the development of new AOPs remains a slow and manually intensive process. Here, we present a faster approach for AOP generation, based on manually curated causal toxicological networks. As a case study, we took a recently published zebrafish developmental neurotoxicity network, which contains causally connected molecular events leading to neuropathologies, and developed two new adverse outcome pathways: Inhibition of Fyna (Src family tyrosine kinase A) leading to increased mortality via decreased eye size (AOP 399 on AOP-Wiki) and GSK3beta (Glycogen synthase kinase 3 beta) inactivation leading to increased mortality via defects in developing inner ear (AOP 410). The approach consists of an automatic separation of the toxicological network into candidate AOPs, filtering the AOPs according to available evidence and length as well as manual development of new AOPs and weight-of-evidence evaluation. The semiautomatic approach described here provides a new opportunity for fast and straightforward AOP development based on large network resources.
Ključne besede: systems toxicology, adverse outcome pathway, casual network, toxicological network, neurotoxicity
Objavljeno v DiRROS: 16.07.2024; Ogledov: 189; Prenosov: 154
.pdf Celotno besedilo (1,65 MB)
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