Browsing by Author "Coecke, Sandra"
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- Building an adverse outcome pathway network for COVID-19Publication . Nymark, Penny; Clerbaux, Laure Alix; Amorim, Maria João; Andronis, Christos; Bernardi, Francesca de; Bezemer, Gillina F. G.; Coecke, Sandra; Gavins, Felicity N. E.; Jacobson, Daniel; Lekka, Eftychia; Margiotta-Casaluci, Luigi; Martens, Marvin; Mayasich, Sally A.; Mortensen, Holly M.; Kim, Young Jun; Sachana, Magdalini; Tanabe, Shihori; Virvilis, Vassilis; Edwards, Stephen W.; Halappanavar, SabinaThe COVID-19 pandemic generated large amounts of data on the disease pathogenesis leading to a need for organizing the vast knowledge in a succinct manner. Between April 2020 and February 2023, the CIAO consortium exploited the Adverse Outcome Pathway (AOP) framework to comprehensively gather and systematically organize published scientific literature on COVID-19 pathology. The project considered 24 pathways relevant for COVID-19 by identifying essential key events (KEs) leading to 19 adverse outcomes observed in patients. While an individual AOP defines causally linked perturbed KEs towards an outcome, building an AOP network visually reflect the interrelatedness of the various pathways and outcomes. In this study, 17 of those COVID-19 AOPs were selected based on quality criteria to computationally derive an AOP network. This primary network highlighted the need to consider tissue specificity and helped to identify missing or redundant elements which were then manually implemented in the final network. Such a network enabled visualization of the complex interactions of the KEs leading to the various outcomes of the multifaceted COVID-19 and confirmed the central role of the inflammatory response in the disease. In addition, this study disclosed the importance of terminology harmonization and of tissue/organ specificity for network building. Furthermore the unequal completeness and quality of information contained in the AOPs highlighted the need for tighter implementation of the FAIR principles to improve AOP findability, accessibility, interoperability and re-usability. Finally, the study underlined that describing KEs specific to SARS-CoV-2 replication and discriminating physiological from pathological inflammation is necessary but requires adaptations to the framework. Hence, based on the challenges encountered, we proposed recommendations relevant for ongoing and future AOP-aligned consortia aiming to build computationally biologically meaningful AOP networks in the context of, but not limited to, viral diseases.
- Mechanisms leading to gut dysbiosis in COVID-19: current evidence and uncertainties based on adverse outcome pathwaysPublication . Clerbaux, Laure Alix; Fillipovska, Julija; Muñoz, Amalia; Petrillo, Mauro; Coecke, Sandra; Amorim, Maria João; Grenga, LuciaAlteration in gut microbiota has been associated with COVID-19. However, the underlying mechanisms remain poorly understood. Here, we outlined three potential interconnected mechanistic pathways leading to gut dysbiosis as an adverse outcome following SARS-CoV-2 presence in the gastrointestinal tract. Evidence from the literature and current uncertainties are reported for each step of the different pathways. One pathway investigates evidence that intestinal infection by SARS-CoV-2 inducing intestinal inflammation alters the gut microbiota. Another pathway links the binding of viral S protein to angiotensin-converting enzyme 2 (ACE2) to the dysregulation of this receptor, essential in intestinal homeostasis—notably for amino acid metabolism—leading to gut dysbiosis. Additionally, SARS-CoV-2 could induce gut dysbiosis by infecting intestinal bacteria. Assessing current evidence within the Adverse Outcome Pathway framework justifies confidence in the proposed mechanisms to support disease management and permits the identification of inconsistencies and knowledge gaps to orient further research.