Prediction of zebrafish embryonic developmental toxicity by integrating omics with adverse outcome pathway

Gou, Xiao; Ma, Cong; Ji, Huimin; Yan, Lu; Wang, Pingping; Wang, Wenwen; Lin, Yiqing; Chatterjee, Nivedita; H, Yu; Zhang, Xiaowei

doi:10.1016/j.jhazmat.2023.130958

Cited by 14 publications

(9 citation statements)

References 57 publications

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“…Predictive models have been widely applied in AOP development, including machine learning (Gou et al 2023) and probabilistic graphical network models (Villeneuve et al 2018). KEs could be screened from a pool of candidate molecular and cellular events using feature selection techniques (Perkins et al 2019a).…”

Section: Resultsmentioning

confidence: 99%

Causal, Predictive or Observational? Different Understandings of Key Event Relationships for Adverse Outcome Pathways and Their Implications on Practice

Zhou,

Pennings,

Sahlin

2024

Preprint

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The difference between predictive and causal relationships has been a question in mechanistic toxicology. The adverse outcome pathways (AOPs) methodology is a mechanistic framework that supports the transition to non-animal methods in risk assessment. AOPs include molecular initiating events, key events, and adverse outcomes, linked by key event relationships (KERs) to infer higher-level outcomes from lower biological levels. To better understand the implications of causal and predictive KERs in AOP development, this study aimed to: 1) analyze the use of the terms describing KERs in key AOP guiding documents, and 2) examine their application in AOP development. Our text analysis on the two documents revealed that KER definitions could involve predictive, causal, or both. Examples were also found from studies of AOP development where KER definition is specified to be observational. The implications of these findings are discussed in the context of KER evaluation. We conducted a literature analysis to assess how these terms are adapted across different stages of AOP development, noting that while the use of various KER definitions aligns with specific research objectives, the methodologies for establishing causality in some studies may be questionable.

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Section: Resultsmentioning

confidence: 99%

Causal, Predictive or Observational? Different Understandings of Key Event Relationships for Adverse Outcome Pathways and Their Implications on Practice

Zhou,

Pennings,

Sahlin

2024

Preprint

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“…We additionally provide auxiliary evidence for the association of KEs with inorganic cadmium in the directed AOP network. In future, integrative data-centric evidence-based approaches can be leveraged to expand the scope of existing AOPs, or develop novel AOPs, which can further enable the derivation of comprehensive and elaborate AOP networks [103][104][105][106][107]. Further experimentation is required to characterize the points-of-departure of cadmium toxicity and that will aid in strengthening chemical regulations, thereby advancing chemical exposome research.…”

Section: Discussionmentioning

confidence: 99%

An integrative data-centric approach to derivation and characterization of an adverse outcome pathway network for cadmium-induced toxicity

Sahoo,

Chivukula,

Ramesh

et al. 2023

Preprint

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Cadmium is a prominent toxic heavy metal that contaminates both terrestrial and aquatic environments. Owing to its high biological half-life and low excretion rates, cadmium causes a variety of adverse biological outcomes. Adverse outcome pathway (AOP) networks were envisioned to systematically capture toxicological information to enable risk assessment and chemical regulation. Here, we leveraged AOP-Wiki and integrated heterogeneous data from four other exposome-relevant resources to build the first AOP network relevant for inorganic cadmium-induced toxicity. From AOP-Wiki, we filtered 309 high confidence AOPs, identified 312 key events (KEs) associated with inorganic cadmium, and thereafter, curated 30 cadmium relevant AOPs (cadmium-AOPs), using a data-centric approach. By constructing the undirected AOP network, we identified a large connected component of 18 cadmium-AOPs. Further, we analyzed the directed network of 59 KEs and 82 key event relationships (KERs) in the largest component using graph-theoretic approaches. Subsequently, we mined published literature using artificial intelligence-based tools to provide auxiliary evidence of cadmium association for all KEs in the largest component. Finally, we performed case studies to verify the rationality of cadmium-induced toxicity in humans and aquatic species. Overall, cadmium-AOP network constructed in this study will aid ongoing research in systems toxicology and chemical exposome.

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“…From a toxicological perspective, omics serve as valuable tools for identifying biomolecular alterations induced by exposure to chemical agents [128]. In comparison to previous approaches, omics techniques present notable advantages, notably the capability to comprehend molecular-level changes by leveraging a wealth of pertinent information.…”

Section: Omics Technologiesmentioning

confidence: 99%

The Zebrafish as an Alternative Animal Model for Ecotoxicological Research and Testing

Braga,

Souza,

Lima

et al. 2024

Braz. arch. biol. technol.

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Anthropogenic interventions have had a compromising effect on environmental health, intensifying the degradation of ecosystems, and the quantity of chemical pollutants released into nature. Therefore, research areas within the scope of environmental assessments and monitoring such as ecotoxicology have contributed to the determination of the toxic potential of contaminants. A small cyprinid known as the zebrafish (Danio rerio), the use of which has exponentially grown, is an alternative vertebrate model for scientific research, mainly in the assessment of environmental risks. The species exhibits several advantages for breeding in a laboratory, in addition to presenting multi-biomarkers of environmental toxicity. Thus, this review aims to present the main characteristics and advantages of working with this species, as well as show studies related to ecotoxicology involving biomarkers of toxicity in zebrafish. The results show a progressive trend towards employing the species in environmental risk analyses, it is an increasingly recommended species in the assessment of the toxicity level of a range of chemical pollutants. The development of future technologies must contribute to scientific advancement, rendering the potential application of this model organism an even more widespread one, which will certainly help in bridging knowledge gaps in various areas of study.

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Prediction of zebrafish embryonic developmental toxicity by integrating omics with adverse outcome pathway

Cited by 14 publications

References 57 publications

Causal, Predictive or Observational? Different Understandings of Key Event Relationships for Adverse Outcome Pathways and Their Implications on Practice

Causal, Predictive or Observational? Different Understandings of Key Event Relationships for Adverse Outcome Pathways and Their Implications on Practice

An integrative data-centric approach to derivation and characterization of an adverse outcome pathway network for cadmium-induced toxicity

The Zebrafish as an Alternative Animal Model for Ecotoxicological Research and Testing

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