Noise-induced bistability in the fate of cancer phenotypic quasispecies: a bit-strings approach

Abstract Tumor cell populations are highly heterogeneous. Such heterogeneity, both at genotypic and phenotypic levels, is a key feature during tumorigenesis. How to investigate the impact of this heterogeneity in the dynamics of tumors cells becomes an important issue. Here we explore a stochastic m...

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Autores principales:	Josep Sardanyés, Tomás Alarcón
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3207f854678f43bcb0537911da90ed80
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spelling	oai:doaj.org-article:3207f854678f43bcb0537911da90ed802021-12-02T11:40:15ZNoise-induced bistability in the fate of cancer phenotypic quasispecies: a bit-strings approach10.1038/s41598-018-19552-22045-2322https://doaj.org/article/3207f854678f43bcb0537911da90ed802018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-19552-2https://doaj.org/toc/2045-2322Abstract Tumor cell populations are highly heterogeneous. Such heterogeneity, both at genotypic and phenotypic levels, is a key feature during tumorigenesis. How to investigate the impact of this heterogeneity in the dynamics of tumors cells becomes an important issue. Here we explore a stochastic model describing the competition dynamics between a pool of heterogeneous cancer cells with distinct phenotypes and healthy cells. This model is used to explore the role of demographic fluctuations on the transitions involving tumor clearance. Our results show that for large population sizes, when demographic fluctuations are negligible, there exists a sharp transition responsible for tumor cells extinction at increasing tumor cells’ mutation rates. This result is consistent with a mean field model developed for the same system. The mean field model reveals only monostability scenarios, in which either the dominance of the tumor cells or the dominance of the healthy cells is found. Interestingly, the stochastic model shows that for small population sizes the monostability behavior disappears, involving the presence of noise-induced bistability. The impact of the initial populations of cells in the fate of the cell populations is investigated, as well as the transient times towards the healthy and the cancer states.Josep SardanyésTomás AlarcónNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Josep Sardanyés Tomás Alarcón Noise-induced bistability in the fate of cancer phenotypic quasispecies: a bit-strings approach
description	Abstract Tumor cell populations are highly heterogeneous. Such heterogeneity, both at genotypic and phenotypic levels, is a key feature during tumorigenesis. How to investigate the impact of this heterogeneity in the dynamics of tumors cells becomes an important issue. Here we explore a stochastic model describing the competition dynamics between a pool of heterogeneous cancer cells with distinct phenotypes and healthy cells. This model is used to explore the role of demographic fluctuations on the transitions involving tumor clearance. Our results show that for large population sizes, when demographic fluctuations are negligible, there exists a sharp transition responsible for tumor cells extinction at increasing tumor cells’ mutation rates. This result is consistent with a mean field model developed for the same system. The mean field model reveals only monostability scenarios, in which either the dominance of the tumor cells or the dominance of the healthy cells is found. Interestingly, the stochastic model shows that for small population sizes the monostability behavior disappears, involving the presence of noise-induced bistability. The impact of the initial populations of cells in the fate of the cell populations is investigated, as well as the transient times towards the healthy and the cancer states.
format	article
author	Josep Sardanyés Tomás Alarcón
author_facet	Josep Sardanyés Tomás Alarcón
author_sort	Josep Sardanyés
title	Noise-induced bistability in the fate of cancer phenotypic quasispecies: a bit-strings approach
title_short	Noise-induced bistability in the fate of cancer phenotypic quasispecies: a bit-strings approach
title_full	Noise-induced bistability in the fate of cancer phenotypic quasispecies: a bit-strings approach
title_fullStr	Noise-induced bistability in the fate of cancer phenotypic quasispecies: a bit-strings approach
title_full_unstemmed	Noise-induced bistability in the fate of cancer phenotypic quasispecies: a bit-strings approach
title_sort	noise-induced bistability in the fate of cancer phenotypic quasispecies: a bit-strings approach
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/3207f854678f43bcb0537911da90ed80
work_keys_str_mv	AT josepsardanyes noiseinducedbistabilityinthefateofcancerphenotypicquasispeciesabitstringsapproach AT tomasalarcon noiseinducedbistabilityinthefateofcancerphenotypicquasispeciesabitstringsapproach
_version_	1718395634021564416

Noise-induced bistability in the fate of cancer phenotypic quasispecies: a bit-strings approach

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