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

In the development of cell-based cancer therapies, quantitative mathematical models of cellular interactions are instrumental in understanding treatment efficacy.Efforts to validate retail-packaged 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 Winter Sports - Gear 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.

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