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stormTB: a web-based simulator of a murine minimal-PBPK model for anti-tuberculosis treatments

Affiliation
Fondazione The Microsoft Research - University of Trento Centre for Computational and Systems Biology (COSBI) ,Rovereto ,Italy
Visintainer, Roberto;
Affiliation
Fondazione The Microsoft Research - University of Trento Centre for Computational and Systems Biology (COSBI) ,Rovereto ,Italy
Fochesato, Anna;
Affiliation
Fondazione The Microsoft Research - University of Trento Centre for Computational and Systems Biology (COSBI) ,Rovereto ,Italy
Boaretti, Daniele;
Affiliation
Fondazione The Microsoft Research - University of Trento Centre for Computational and Systems Biology (COSBI) ,Rovereto ,Italy
Giampiccolo, Stefano;
Affiliation
Gates Medical Research Institute ,Cambridge ,MA ,United States
Watson, Shayne;
Affiliation
Gates Medical Research Institute ,Cambridge ,MA ,United States
Levi, Micha;
Affiliation
Fondazione The Microsoft Research - University of Trento Centre for Computational and Systems Biology (COSBI) ,Rovereto ,Italy
Reali, Federico;
Affiliation
Fondazione The Microsoft Research - University of Trento Centre for Computational and Systems Biology (COSBI) ,Rovereto ,Italy
Marchetti, Luca

Introduction Tuberculosis (TB) poses a significant threat to global health, with millions of new infections and approximately one million deaths annually. Various modeling efforts have emerged, offering tailored data-driven and physiologically-based solutions for novel and historical compounds. However, this diverse modeling panorama may lack consistency, limiting result comparability. Drug-specific models are often tied to commercial software and developed on various platforms and languages, potentially hindering access and complicating the comparison of different compounds. Methods This work introduces stormTB: SimulaTOr of a muRine Minimal-pbpk model for anti-TB drugs. It is a web-based interface for our minimal physiologically based pharmacokinetic (mPBPK) platform, designed to simulate custom treatment scenarios for tuberculosis in murine models. The app facilitates visual comparisons of pharmacokinetic profiles, aiding in assessing drug-dose combinations. Results The mPBPK model, supporting 11 anti-TB drugs, offers a unified perspective, overcoming the potential inconsistencies arising from diverse modeling efforts. The app, publicly accessible, provides a user-friendly environment for researchers to conduct what-if analyses and contribute to collective TB eradication efforts. The tool generates comprehensive visualizations of drug concentration profiles and pharmacokinetic/pharmacodynamic indices for TB-relevant tissues, empowering researchers in the quest for more effective TB treatments. stormTB is freely available at the link: https://apps.cosbi.eu/stormTB .

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License Holder: Copyright © 2025 Visintainer, Fochesato, Boaretti, Giampiccolo, Watson, Levi, Reali and Marchetti.

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