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This article is the author’s final published version in Computational and Structural Biotechnology Journal, Volume 18, November 2019, Pages 45-51.

The published version is available at Copyright © Sang et al.


Intratumoral heterogeneity (ITH) has been regarded as a key cause of the failure and resistance of cancer therapy, but how it behaves and functions remains unclear. Advances in single-cell analysis have facilitated the collection of a massive amount of data about genetic and molecular states of individual cancer cells, providing a fuel to dissect the mechanistic organization of ITH at the molecular, metabolic and positional level. Taking advantage of these data, we propose a computational model to rewire up a topological network of cell-cell interdependences and interactions that operate within a tumor mass. The model is grounded on the premise of game theory that each interactive cell (player) strives to maximize its fitness by pursuing a "rational self-interest" strategy, war or peace, in a way that senses and alters other cells to respond properly. By integrating this idea with genome-wide association studies for intratumoral cells, the model is equipped with a capacity to visualize, annotate and quantify how somatic mutations mediate ITH and the network of intratumoral interactions. Taken together, the model provides a topological flow by which cancer cells within a tumor cooperate or compete with each other to downstream pathogenesis. This topological flow can be potentially used as a blueprint for genetically intervening the pattern and strength of cell-cell interactions towards cancer control.

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Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

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