AOP-networkFinder — A versatile tool for the reconstruction and visualization of adverse Outcome Pathway networks from AOP-Wiki

Bioinformatics Advances, Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

Abstract Motivation The AOP-Wiki, a knowledge database for Adverse Outcome Pathways (AOPs), requires an efficient way to present overview of its content the reconstruction networks by experts in given domain. We have developed AOP-networkFinder, user-friendly tool that retrieves AOPs interest, allows network generation and cleaning, finally visualizes built around retrieved AOPs. Our constructs AOP connecting use same Key Events (KEs) versatile but controlled manner. Genes related these KEs are also displayed. constructed can then be exported as images or Cytoscape further fine-tuning statistical analysis. Results AOP-networkFinder users comprehensively identify relationships between visualize overall structure both quickly easily. This is immensely beneficial researchers who need understand complex interplay different pathway they studying helps them build interest while logging relevant information about changes within network. These efforts line with FAIR principles, which crucial attributes any databases tools optimizing (re)use dynamically changing landscape AOP-Wiki. Availability implementation open-source application available online at aop-networkfinder.no, ‘Computational Toxicology Norwegian Institute Public Health’ Zenodo community DOI 10.5281/zenodo.11068434, GitHub repository github.com/folkehelseinstituttet/AOPnetworkFinder_v1, well Docker image hub.docker.com/r/nurre123/aop_network_finder. software under GNU Affero General License (AGPL), v3.0. uses AOP-Wiki SPARQL endpoint retrieve data.

Язык: Английский

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A developmental neurotoxicity adverse outcome pathway (DNT‐AOP) with voltage gate sodium channel (VGSC) inhibition as a molecular initiating event (MiE)

EFSA Journal, Год журнала: 2024, Номер 22(8)

Опубликована: Авг. 1, 2024

Abstract The adverse outcome pathway (AOP) framework serves as a practical tool for organising scientific knowledge that can be used to infer cause–effect relationships between stressor events and toxicity outcomes in intact organisms. However, major challenge the broader application of AOP concept within regulatory toxicology is development robust AOPs withstand peer review acceptance. This mainly due considerable amount work required substantiate modular units complete AOP, which take years from inception completion. methodology here consisted an initial assessment single chemical hazard using Integrated Approach Testing Assessment (IATA) framework. An evidence‐based approach was then gather empirical evidence combining systematic literature methods with expert ensure effectiveness methodology. structured assured transparency, objectivity comprehensiveness, included elicitation evaluation key event (KERs). stepwise led begins binding chemicals Voltage Gate Sodium Channels (VGSC/Nav) during mammalian leading consequences neurodevelopment evidenced deficits cognitive functions. Disruption formation precise neural circuits by alterations VGSC kinetics perinatal stages brain may also underlie neurodevelopmental disorders. Gaps our understanding include specific critical developmental windows quantitative relationship subsequent disruption function. Despite limited information at all KER levels, applications this DNT have been identified.

Язык: Английский

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Using transcriptomics data and adverse outcome pathway networks to explore endocrine disrupting properties of Cadmium and PCB-126

Environment International, Год журнала: 2025, Номер 197, С. 109352 - 109352

Опубликована: Фев. 26, 2025

Язык: Английский

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Modeling omics dose-response at the pathway level with DoseRider

Computational and Structural Biotechnology Journal, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

The generation of omics data sets has become an important approach in modern pharmacological and toxicological research as it can provide mechanistic quantitative information on a large scale. Analyses these frequently revealed non-linear dose-response relationship underscoring the importance modeling process to infer biological exposure limits. A number tools have been developed for various thresholds defined representation effect substance, such effective concentrations or benchmark doses (BMD). Here we present DoseRider easy-to-use web application companion R package linear assessment BMD at level pathways signatures using generalized mixed models. This allows analyze custom provided multi-omics RNA sequencing metabolomics its annotation collection gene from species. Moreover, introduce concept trend change (TCDs) numerical descriptor effects derived complex curves. usability was demonstrated by analyses bisphenol AF (BPAF) treatment human breast cancer cell line (MCF-7) 8 different chemical genetic perturbations (MSigDB). BPAF set genes upregulated estrogen 0.2 µM (95 %-CI 0.1-0.5 µM) lowest TCD (TCD1) 0.003 0.0006-0.01 µM). comprehensive presentation results underlines suitability system pharmacogenomics, toxicogenomics, applications beyond.

Язык: Английский

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Assessment of immunotoxicity in the 21st century: where we are and what we need to replace animals

Current Opinion in Toxicology, Год журнала: 2025, Номер unknown, С. 100529 - 100529

Опубликована: Апрель 1, 2025

Язык: Английский

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Quantitative Systems Toxicology

Springer eBooks, Год журнала: 2024, Номер unknown, С. 1 - 11

Опубликована: Янв. 1, 2024

Язык: Английский

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Utilization of human stem cells to examine neurotoxic impacts on differentiation

Advances in neurotoxicology, Год журнала: 2024, Номер unknown, С. 137 - 172

Опубликована: Янв. 1, 2024

Язык: Английский

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Quantitative Systems Toxicology

Springer eBooks, Год журнала: 2024, Номер unknown, С. 2573 - 2583

Опубликована: Янв. 1, 2024

Язык: Английский

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Implementing AOPs use for Pesticide Neurotoxicity Assessment

Current Opinion in Toxicology, Год журнала: 2024, Номер unknown, С. 100505 - 100505

Опубликована: Окт. 1, 2024

Язык: Английский

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