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WijayaTrairatphisan2021 - Logic-ODE model of stress signaling in DILI

ABSTRACT: We established a comprehensive temporal dynamic response profile of a large set of BAC-GFP HepG2 cell lines representing the following components of stress signaling: i) unfolded protein response (UPR) [ATF4, XBP1, BIP and CHOP]; ii) oxidative stress [NRF2, SRXN1, HMOX1]; iii) DNA damage [P53, P21, BTG2, MDM2]; and iv) NF-κB pathway [A20, ICAM1]. Using logic-based ordinary differential equation (Logic-ODE), we modelled the dynamic profiles of the different stress responses and extracted specific descriptors potentially predicting the progressive outcomes. Please see the most updated version on GitHub: https://github.com/saezlab/LogicODE_GFP_SR

SUBMITTER: Panuwat Trairatphisan  

PROVIDER: MODEL2206070001 | BioModels | 2022-08-02

REPOSITORIES: BioModels

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Integration of temporal single cell cellular stress response activity with logic-ODE modeling reveals activation of ATF4-CHOP axis as a critical predictor of drug-induced liver injury.

Wijaya Lukas Surya LS   Trairatphisan Panuwat P   Gabor Attila A   Niemeijer Marije M   Keet Jason J   Alcalà Morera Ariadna A   Snijders Kirsten E KE   Wink Steven S   Yang Huan H   Schildknecht Stefan S   Stevens James L JL   Bouwman Peter P   Kamp Hennicke H   Hengstler Jan J   Beltman Joost J   Leist Marcel M   Le Dévédec Sylvia S   Saez-Rodriguez Julio J   van de Water Bob B  

Biochemical pharmacology 20210504

Drug-induced liver injury (DILI) is the most prevalent adversity encountered in drug development and clinical settings leading to urgent needs to understand the underlying mechanisms. In this study, we have systematically investigated the dynamics of the activation of cellular stress response pathways and cell death outcomes upon exposure of a panel of liver toxicants using live cell imaging of fluorescent reporter cell lines. We established a comprehensive temporal dynamic response profile of a  ...[more]

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