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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. 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GPU cluster for high performance computing. In: SC\u201904: Proceedings of the 2004 ACM\/IEEE Conference on Supercomputing. IEEE; 2004. p. 47\u201347. https:\/\/doi.org\/10.1109\/SC.2004.26","DOI":"10.1109\/SC.2004.26"},{"issue":"5659","key":"pcbi.1008266.ref065","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1126\/science.1093411","article-title":"Evolutionary dynamics of biological games","volume":"303","author":"MA Nowak","year":"2004","journal-title":"Science"},{"issue":"3","key":"pcbi.1008266.ref066","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nrc1295","article-title":"Dynamics of cancer progression","volume":"4","author":"F Michor","year":"2004","journal-title":"Nature Reviews Cancer"},{"issue":"1","key":"pcbi.1008266.ref067","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1158\/0008-5472.CAN-12-2273","article-title":"Single-molecule genomic data delineate patient-specific tumor profiles and cancer stem cell organization","volume":"73","author":"A Sottoriva","year":"2013","journal-title":"Cancer Research"},{"issue":"25","key":"pcbi.1008266.ref068","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1021\/j100540a008","article-title":"Exact stochastic simulation of coupled chemical reactions","volume":"81","author":"DT Gillespie","year":"1977","journal-title":"The Journal of Physical Chemistry"},{"issue":"5","key":"pcbi.1008266.ref069","doi-asserted-by":"crossref","first-page":"052713","DOI":"10.1103\/PhysRevE.88.052713","article-title":"Incorporating spatial correlations into multispecies mean-field models","volume":"88","author":"DC Markham","year":"2013","journal-title":"Physical Review E"},{"issue":"3","key":"pcbi.1008266.ref070","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1006\/tpbi.1994.1032","article-title":"The importance of being discrete (and spatial)","volume":"46","author":"R Durrett","year":"1994","journal-title":"Theoretical Population 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Genetics"},{"issue":"2","key":"pcbi.1008266.ref074","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1172\/JCI40724","article-title":"Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype","volume":"120","author":"SY Park","year":"2010","journal-title":"The Journal of Clinical Investigation"},{"issue":"1","key":"pcbi.1008266.ref075","doi-asserted-by":"crossref","first-page":"9332","DOI":"10.1038\/s41598-019-45863-z","article-title":"Interplay of Darwinian selection, Lamarckian induction and microvesicle transfer on drug resistance in cancer","volume":"9","author":"A \u00c1lvarez-Arenas","year":"2019","journal-title":"Sci Rep"},{"issue":"7","key":"pcbi.1008266.ref076","doi-asserted-by":"crossref","first-page":"e1006778","DOI":"10.1371\/journal.pcbi.1006778","article-title":"Computational design of improved standardized chemotherapy protocols for grade II oligodendrogliomas","volume":"15","author":"VM 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