Abstract

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.

Original languageEnglish (US)
Pages (from-to)45-51
Number of pages7
JournalComputational and Structural Biotechnology Journal
Volume18
DOIs
StatePublished - 2020

Fingerprint

Tumors
Neoplasms
Cells
Blueprints
Game theory
Game Theory
Single-Cell Analysis
Genes
Genome-Wide Association Study
Molecular Biology
Organizations
Mutation
Therapeutics
Warfare

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biophysics
  • Structural Biology
  • Biochemistry
  • Genetics
  • Computer Science Applications

Cite this

Sang, Mengmeng ; Rice, Shawn ; Jiang, Libo ; Liu, Xin ; Gragnoli, Claudia ; Belani, Chandra P. ; Wu, Rongling. / A rewiring model of intratumoral interaction networks. In: Computational and Structural Biotechnology Journal. 2020 ; Vol. 18. pp. 45-51.
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A rewiring model of intratumoral interaction networks. / Sang, Mengmeng; Rice, Shawn; Jiang, Libo; Liu, Xin; Gragnoli, Claudia; Belani, Chandra P.; Wu, Rongling.

In: Computational and Structural Biotechnology Journal, Vol. 18, 2020, p. 45-51.

Research output: Contribution to journalReview article

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AU - Rice, Shawn

AU - Jiang, Libo

AU - Liu, Xin

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AU - Belani, Chandra P.

AU - Wu, Rongling

PY - 2020

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