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Using interactive platforms to encode, manage and explore immune-related adverse outcome pathways

Mazein, Alexander ; Shoaib, Muhammad ; Alb, Miriam ; Sakellariou, Christina LU orcid ; Sommer, Charline ; Sewald, Katherina ; Reiche, Kristin ; Gogesch, Patricia ; Roser, Luise A. and Ortega Iannazzo, Samira , et al. (2024) In Journal of Immunotoxicology 21(sup1). p.5-12
Abstract

This work focuses on the need for modeling and predicting adverse outcomes in immunotoxicology to improve nonclinical assessments of the safety of immunomodulatory therapies. The integrated approach includes, first, the adverse outcome pathway concept established in the toxicology field, and, second, the systems medicine disease map approach for describing molecular mechanisms involved in a particular pathology. The proposed systems immunotoxicology workflow is illustrated with chimeric antigen receptor (CAR) T cell treatment as a use case. To this end, the linear adverse outcome pathway (AOP) is expanded into a molecular interaction model in standard systems biology formats. Then it is shown how knowledge related to immunotoxic events... (More)

This work focuses on the need for modeling and predicting adverse outcomes in immunotoxicology to improve nonclinical assessments of the safety of immunomodulatory therapies. The integrated approach includes, first, the adverse outcome pathway concept established in the toxicology field, and, second, the systems medicine disease map approach for describing molecular mechanisms involved in a particular pathology. The proposed systems immunotoxicology workflow is illustrated with chimeric antigen receptor (CAR) T cell treatment as a use case. To this end, the linear adverse outcome pathway (AOP) is expanded into a molecular interaction model in standard systems biology formats. Then it is shown how knowledge related to immunotoxic events can be integrated, encoded, managed, and explored to benefit the research community. The map is accessible online at https://imsavar.elixir-luxembourg.orgvia the MINERVA Platform for browsing, commenting, and data visualization. Our work transforms a graphical illustration of an AOP into a digitally structured and standardized form, featuring precise and controlled vocabulary and supporting reproducible computational analyses. Because of annotations to source literature and databases, the map can be further expanded to match the evolving knowledge and research questions.

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@article{250aba3c-b9cd-4eb6-8e3c-6342a7d373ca,
  abstract     = {{<p>This work focuses on the need for modeling and predicting adverse outcomes in immunotoxicology to improve nonclinical assessments of the safety of immunomodulatory therapies. The integrated approach includes, first, the adverse outcome pathway concept established in the toxicology field, and, second, the systems medicine disease map approach for describing molecular mechanisms involved in a particular pathology. The proposed systems immunotoxicology workflow is illustrated with chimeric antigen receptor (CAR) T cell treatment as a use case. To this end, the linear adverse outcome pathway (AOP) is expanded into a molecular interaction model in standard systems biology formats. Then it is shown how knowledge related to immunotoxic events can be integrated, encoded, managed, and explored to benefit the research community. The map is accessible online at https://imsavar.elixir-luxembourg.orgvia the MINERVA Platform for browsing, commenting, and data visualization. Our work transforms a graphical illustration of an AOP into a digitally structured and standardized form, featuring precise and controlled vocabulary and supporting reproducible computational analyses. Because of annotations to source literature and databases, the map can be further expanded to match the evolving knowledge and research questions.</p>}},
  author       = {{Mazein, Alexander and Shoaib, Muhammad and Alb, Miriam and Sakellariou, Christina and Sommer, Charline and Sewald, Katherina and Reiche, Kristin and Gogesch, Patricia and Roser, Luise A. and Ortega Iannazzo, Samira and Sheth, Sapna and Schiffmann, Susanne and Waibler, Zoe and Neuhaus, Vanessa and Dehmel, Susann and Satagopam, Venkata and Schneider, Reinhard and Ostaszewski, Marek and Gu, Wei}},
  issn         = {{1547-691X}},
  keywords     = {{adverse outcome pathway; AOP; CAR T cells; chimeric antigen receptor; CRS; cytokine release syndrome; disease mechanisms; immunomodulatory therapies; systems biology}},
  language     = {{eng}},
  number       = {{sup1}},
  pages        = {{5--12}},
  publisher    = {{Informa Healthcare}},
  series       = {{Journal of Immunotoxicology}},
  title        = {{Using interactive platforms to encode, manage and explore immune-related adverse outcome pathways}},
  url          = {{http://dx.doi.org/10.1080/1547691X.2024.2345154}},
  doi          = {{10.1080/1547691X.2024.2345154}},
  volume       = {{21}},
  year         = {{2024}},
}