دورية أكاديمية

Data driven model discovery and interpretation for CAR T-cell killing using sparse identification and latent variables

التفاصيل البيبلوغرافية
العنوان: Data driven model discovery and interpretation for CAR T-cell killing using sparse identification and latent variables
المؤلفون: Alexander B. Brummer, Agata Xella, Ryan Woodall, Vikram Adhikarla, Heyrim Cho, Margarita Gutova, Christine E. Brown, Russell C. Rockne
المصدر: Frontiers in Immunology, Vol 14 (2023)
بيانات النشر: Frontiers Media S.A., 2023.
سنة النشر: 2023
المجموعة: LCC:Immunologic diseases. Allergy
مصطلحات موضوعية: dynamical systems, latent variables, CAR T-cells, antigen binding, allee effect, SINDy, Immunologic diseases. Allergy, RC581-607
الوصف: In the development of cell-based cancer therapies, quantitative mathematical models of cellular interactions are instrumental in understanding treatment efficacy. Efforts to validate and interpret mathematical models of cancer cell growth and death hinge first on proposing a precise mathematical model, then analyzing experimental data in the context of the chosen model. In this work, we present the first application of the sparse identification of non-linear dynamics (SINDy) algorithm to a real biological system in order discover cell-cell interaction dynamics in in vitro experimental data, using chimeric antigen receptor (CAR) T-cells and patient-derived glioblastoma cells. By combining the techniques of latent variable analysis and SINDy, we infer key aspects of the interaction dynamics of CAR T-cell populations and cancer. Importantly, we show how the model terms can be interpreted biologically in relation to different CAR T-cell functional responses, single or double CAR T-cell-cancer cell binding models, and density-dependent growth dynamics in either of the CAR T-cell or cancer cell populations. We show how this data-driven model-discovery based approach provides unique insight into CAR T-cell dynamics when compared to an established model-first approach. These results demonstrate the potential for SINDy to improve the implementation and efficacy of CAR T-cell therapy in the clinic through an improved understanding of CAR T-cell dynamics.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1664-3224
العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1115536/fullTest; https://doaj.org/toc/1664-3224Test
DOI: 10.3389/fimmu.2023.1115536
الوصول الحر: https://doaj.org/article/3ed9f3f43ccd4e5b86bbe4ee26323978Test
رقم الانضمام: edsdoj.3ed9f3f43ccd4e5b86bbe4ee26323978
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:16643224
DOI:10.3389/fimmu.2023.1115536