Building an Adverse Outcome Pathway network for COVID-19 DOI Creative Commons
Penny Nymark, Laure‐Alix Clerbaux, Maria João Amorim

и другие.

Frontiers in Systems Biology, Год журнала: 2024, Номер 4

Опубликована: Июнь 7, 2024

The COVID-19 pandemic generated large amounts of data on the disease pathogenesis leading to a need for organizing vast knowledge in succinct manner. Between April 2020 and February 2023, CIAO consortium exploited Adverse Outcome Pathway (AOP) framework comprehensively gather systematically organize published scientific literature pathology. project considered 24 pathways relevant by identifying essential key events (KEs) 19 adverse outcomes observed patients. While an individual AOP defines causally linked perturbed KEs towards outcome, building network visually reflect interrelatedness various outcomes. In this study, 17 those AOPs were selected based quality criteria computationally derive network. This primary highlighted consider tissue specificity helped identify missing or redundant elements which then manually implemented final Such enabled visualization complex interactions multifaceted confirmed central role inflammatory response disease. addition, study disclosed importance terminology harmonization tissue/organ building. Furthermore unequal completeness information contained tighter implementation FAIR principles improve findability, accessibility, interoperability re-usability. Finally, underlined that describing specific SARS-CoV-2 replication discriminating physiological from pathological inflammation is necessary but requires adaptations framework. Hence, challenges encountered, we proposed recommendations ongoing future AOP-aligned consortia aiming build biologically meaningful networks context of, not limited to, viral diseases.

Язык: Английский

Advancing the quantitative understanding of Adverse Outcome Pathways: current status, methodologies, and future directions DOI Creative Commons
Jaeseong Jeong, M. D. Gasparyan, Jinhee Choi

и другие.

Environmental Toxicology and Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 6, 2025

Abstract An adverse outcome pathway (AOP) framework maps the sequence of events leading to outcomes from chemical exposures, providing a mechanistic understanding often absent in traditional methods. The quantitative AOP (qAOP) advances by integrating data and mathematical modeling, thereby more precise comprehension relationships between molecular initiating events, key outcomes. This review critically examines three primary methodologies: systems toxicology, regression Bayesian network highlighting their strengths, limitations, specific requirements within toxicology. Through an analysis current methodologies challenges, this emphasizes integration experimental computational approaches elucidate event proposes strategies for overcoming limitations through standardized protocols advanced tools. By outlining future research directions potential qAOPs transform risk assessment, aims contribute advancement regulatory science protection public health environment.

Язык: Английский

Процитировано

1
Beyond chemicals: Opportunities and challenges of integrating non-chemical stressors in adverse outcome pathways DOI Creative Commons
Laure‐Alix Clerbaux, Julija Filipovska, Penny Nymark

и другие.

ALTEX, Год журнала: 2023, Номер unknown

Опубликована: Янв. 1, 2023

The adverse outcome pathways (AOPs) were developed to accelerate evidence-based chemical risk assessment by leveraging data from new approach methodologies. Thanks their stressor-agnostic approach, AOPs seen as instrumental in other fields. Here, we present that report non-chemical stressors along with the challenges encountered for development. Challenges regarding linked nanomaterials include non-specific molecular initiating events, limited understanding of nanomaterial biodistribution, and needs adaptations silico modeling testing systems. Development radiation face how incorporate ionizing events type, dose rate, energy deposition, account targeting multiple macromolecules. COVID-19 required inclusion SARS-CoV-2-specific replicative steps capture essential driving disease. Developing evaluate efficacy toxicity cell therapies necessitates addressing cellular nature therapeutic function stressor. Finally, emerging biological like microbial pesticides can learn AOPs. We further discuss needed expand AOP applicability beyond chemicals are mainly at levels while downstream key tissue or organ level, such inflammation, shared many initiated various stressors. In conclusion, although it is challenging integrate within AOPs, this expands opportunities real-world scenarios, identify vulnerable individuals, bridge knowledge on mechanisms adversity. Plain language summaryThe pathway (AOP) framework was help predict whether have toxic effects humans. Structuring available information an accessible database reduce animal testing. usually path interaction a stressor, chemical, human body outcome, e.g., disease symptom. concept has now been expanded nanomaterials, radiation, viruses, cells used treat patients, microorganisms employed pesticides. use these need be accommodated point out share inflammation By integrating into framework, scenarios where people may exposed different stressor types considered, individuals identified, compounded.

Язык: Английский

Процитировано

9
Chemicals regulation and non-animal methods: displacing the gold standard DOI Creative Commons
Annamaria Carusi

Wellcome Open Research, Год журнала: 2024, Номер 9, С. 167 - 167

Опубликована: Сен. 2, 2024

Regulating industrial chemicals in foodstuffs and consumer products is a major aspect of protecting populations against health risks. Non-animal testing methods are an essential part the radical change to framework for toxicity that long overdue global economies. This paper discusses reasons why drive reduce animal chemical safety so difficult achieve, as perceived by those who closely involved regulations different capacities. Progress slow, despite fact ethico-legal conditions move away from largely place, scientific arguments paradigm testing, reliance on studies. I present empirical data drawn two studies European Commission context promoting non-animal methods. The aim modest. It foreground voices deal with science regulation day-to-day basis, rather than offer theoretical what heard them. synthesis main challenges faced alternatives, these people stakeholder groups dealing regulation. show where there pockets agreement between stakeholders, disagreements lie. In particular dispute disagreement over counts validation alternative tests, implication traditional ‘gold standard’ testing. Finally, suggest shift demonstrates need concept be broadened purely techno-scientific definition, more explictly understood demand trust acceptance, attention given complex social, institutional economic settings which it operates.

Язык: Английский

Процитировано

1
Report of the 3rd and 4th Mystery of Reactive Oxygen Species Conference DOI Creative Commons
Shihori Tanabe

ALTEX, Год журнала: 2023, Номер unknown, С. 689 - 693

Опубликована: Янв. 1, 2023

The main MoR discussion led to further suggestions on KE terminology, including ensuring coherence directionality in terms of the descriptions (e.g., specifying increase, decrease, altered, no direction, etc.) and clarifying differences ROS reactive oxygen nitrogen species (RONS), enzymatic non-enzymatic events.The consortium highlighted importance role as a an associative event AOP framework.Additionally, participants modification macromolecules from resultant RONS generation lipid peroxidation) relevant endpoint include KE.The possibility grouping ROS-related KEs framework needs be discussed further.

Язык: Английский

Процитировано

2
Chemicals regulation and non-animal methods: displacing the gold standard DOI Creative Commons
Annamaria Carusi

Wellcome Open Research, Год журнала: 2024, Номер 9, С. 167 - 167

Опубликована: Март 20, 2024

Regulating industrial chemicals in foodstuffs and consumer products is a major aspect of protecting populations against health risks. Non-animal testing methods are an essential part the radical change to framework for toxicity that long overdue global economies. This paper discusses reasons why drive reduce animal chemical safety so difficult achieve, as perceived by those who closely involved regulations different capacities. Progress slow, despite fact ethico-legal conditions move away from largely place, scientific arguments paradigm testing, reliance on studies. I present empirical data drawn two studies European Commission context promoting non-animal methods. The aim modest. It foreground voices deal with science regulation day-to-day basis, rather than offer theoretical what heard them. synthesis main challenges faced alternatives, these people stakeholder groups dealing regulation. show where there pockets agreement between stakeholders, disagreements lie. In particular dispute disagreement over counts validation alternative tests, implication traditional ‘gold standard’ testing. Finally, suggest shift demonstrates need concept be broadened purely techno-scientific definition, more explictly understood demand trust acceptance, attention given complex social, institutional economic settings which it operates.

Язык: Английский

Процитировано

0
Building an Adverse Outcome Pathway network for COVID-19 DOI Creative Commons
Penny Nymark, Laure‐Alix Clerbaux, Maria João Amorim

и другие.

Frontiers in Systems Biology, Год журнала: 2024, Номер 4

Опубликована: Июнь 7, 2024

The COVID-19 pandemic generated large amounts of data on the disease pathogenesis leading to a need for organizing vast knowledge in succinct manner. Between April 2020 and February 2023, CIAO consortium exploited Adverse Outcome Pathway (AOP) framework comprehensively gather systematically organize published scientific literature pathology. project considered 24 pathways relevant by identifying essential key events (KEs) 19 adverse outcomes observed patients. While an individual AOP defines causally linked perturbed KEs towards outcome, building network visually reflect interrelatedness various outcomes. In this study, 17 those AOPs were selected based quality criteria computationally derive network. This primary highlighted consider tissue specificity helped identify missing or redundant elements which then manually implemented final Such enabled visualization complex interactions multifaceted confirmed central role inflammatory response disease. addition, study disclosed importance terminology harmonization tissue/organ building. Furthermore unequal completeness information contained tighter implementation FAIR principles improve findability, accessibility, interoperability re-usability. Finally, underlined that describing specific SARS-CoV-2 replication discriminating physiological from pathological inflammation is necessary but requires adaptations framework. Hence, challenges encountered, we proposed recommendations ongoing future AOP-aligned consortia aiming build biologically meaningful networks context of, not limited to, viral diseases.

Язык: Английский

Процитировано

0