RT Journal Article T1 A mesoscopic simulator to uncover heterogeneity and evolutionary dynamics in tumors A1 Jiménez-Sánchez, Juan A1 Martínez-Rubio, Álvaro A1 Popov, Anton A1 Pérez-Beteta, Julián A1 Azimzade, Youness A1 Molina-García, David A1 Belmonte-Beitia, Juan A1 Calvo, Gabriel F. A1 Pérez-García, Víctor M. K1 Genetic heterogeneity K1 Neoplasms K1 Brain neoplasms K1 Computational biology K1 Computer simulation K1 Cell division K1 Heterogeneidad genética K1 Neoplasias K1 Neoplasias encefálicas K1 Biología computacional K1 Simulación por ordenador K1 División celular AB Increasingly complex in silico modeling approaches offer a way to simultaneously access cancerous processes at different spatio-temporal scales. High-level models, such as those based on partial differential equations, are computationally affordable and allow large tumor sizes and long temporal windows to be studied, but miss the discrete nature of many key underlying cellular processes. Individual-based approaches provide a much more detailed description of tumors, but have difficulties when trying to handle full-sized real cancers. Thus, there exists a trade-off between the integration of macroscopic and microscopic information, now widely available, and the ability to attain clinical tumor sizes. In this paper we put forward a stochastic mesoscopic simulation framework that incorporates key cellular processes during tumor progression while keeping computational costs to a minimum. Our framework captures a physical scale that allows both the incorporation of microscopic information, tracking the spatio-temporal emergence of tumor heterogeneity and the underlying evolutionary dynamics, and the reconstruction of clinically sized tumors from high-resolution medical imaging data, with the additional benefit of low computational cost. We illustrate the functionality of our modeling approach for the case of glioblastoma, a paradigm of tumor heterogeneity that remains extremely challenging in the clinical setting. YR 2021 FD 2021-02-10 LK http://hdl.handle.net/10668/4454 UL http://hdl.handle.net/10668/4454 LA en NO Jiménez-Sánchez J, Martínez-Rubio Á, Popov A, Pérez-Beteta J, Azimzade Y, Molina-García D, et al. A mesoscopic simulator to uncover heterogeneity and evolutionary dynamics in tumors. PLOS Comput Biol. 2021 Feb 10;17(2):e1008266 DS RISalud RD Apr 20, 2025