Dataset Information

A unified simulation model for understanding the diversity of cancer evolution.

ABSTRACT: Because cancer evolution underlies the therapeutic difficulties of cancer, it is clinically important to understand the evolutionary dynamics of cancer. Thus far, a number of evolutionary processes have been proposed to be working in cancer evolution. However, there exists no simulation model that can describe the different evolutionary processes in a unified manner. In this study, we constructed a unified simulation model for describing the different evolutionary processes and performed sensitivity analysis on the model to determine the conditions in which cancer growth is driven by each of the different evolutionary processes. Our sensitivity analysis has successfully provided a series of novel insights into the evolutionary dynamics of cancer. For example, we found that, while a high neutral mutation rate shapes neutral intratumor heterogeneity (ITH) characterized by a fractal-like pattern, a stem cell hierarchy can also contribute to shaping neutral ITH by apparently increasing the mutation rate. Although It has been reported that the evolutionary principle shaping ITH shifts from selection to accumulation of neutral mutations during colorectal tumorigenesis, our simulation revealed the possibility that this evolutionary shift is triggered by drastic evolutionary events that occur in a short time and confer a marked fitness increase on one or a few cells. This result helps us understand that each process works not separately but simultaneously and continuously as a series of phases of cancer evolution. Collectively, this study serves as a basis to understand in greater depth the diversity of cancer evolution.

SUBMITTER: Niida A

PROVIDER: S-EPMC7150545 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A unified simulation model for understanding the diversity of cancer evolution.

Niida Atsushi A Hasegawa Takanori T Innan Hideki H Shibata Tatsuhiro T Mimori Koshi K Miyano Satoru S

PeerJ 20200408

Because cancer evolution underlies the therapeutic difficulties of cancer, it is clinically important to understand the evolutionary dynamics of cancer. Thus far, a number of evolutionary processes have been proposed to be working in cancer evolution. However, there exists no simulation model that can describe the different evolutionary processes in a unified manner. In this study, we constructed a unified simulation model for describing the different evolutionary processes and performed sensiti ...[more]

PMID: 32296600

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Project description:Here, we aim to provide a comprehensive and up-to-date overview of the most significant outcomes in the literature regarding the origin of Phaseolus genus, the geographical distribution of the wild species, the domestication process, and the wide spread out of the centers of origin. Phaseolus can be considered as a unique model for the study of crop evolution, and in particular, for an understanding of the convergent phenotypic evolution that occurred under domestication. The almost unique situation that characterizes the Phaseolus genus is that five of its ?70 species have been domesticated (i.e., Phaseolus vulgaris, P. coccineus, P. dumosus, P. acutifolius, and P. lunatus), and in addition, for P. vulgaris and P. lunatus, the wild forms are distributed in both Mesoamerica and South America, where at least two independent and isolated episodes of domestication occurred. Thus, at least seven independent domestication events occurred, which provides the possibility to unravel the genetic basis of the domestication process not only among species of the same genus, but also between gene pools within the same species. Along with this, other interesting features makes Phaseolus crops very useful in the study of evolution, including: (i) their recent divergence, and the high level of collinearity and synteny among their genomes; (ii) their different breeding systems and life history traits, from annual and autogamous, to perennial and allogamous; and (iii) their adaptation to different environments, not only in their centers of origin, but also out of the Americas, following their introduction and wide spread through different countries. In particular for P. vulgaris this resulted in the breaking of the spatial isolation of the Mesoamerican and Andean gene pools, which allowed spontaneous hybridization, thus increasing of the possibility of novel genotypes and phenotypes. This knowledge that is associated to the genetic resources that have been conserved ex situ and in situ represents a crucial tool in the hands of researchers, to preserve and evaluate this diversity, and at the same time, to identify the genetic basis of adaptation and to develop new improved varieties to tackle the challenges of climate change, and food security and sustainability.

Dataset Information

A unified simulation model for understanding the diversity of cancer evolution.

Publications

A unified simulation model for understanding the diversity of cancer evolution.

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