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Koshi Mimori

Publications and source records attributed to Koshi Mimori.

2 recordsLinked to original sources

phyC: Clustering cancer evolutionary trees

MotivationMulti-regional sequencing provides new opportunities to investigate genetic heterogeneity within or between common tumors from an evolutionary perspective. Several state-of-the-art methods have been proposed for reconstructing cancer sub-clonal evolutionary trees based on multi-regional sequencing data to develop models of cancer evolution. However, the methods developed thus far are not sufficient to characterize and interpret the diversity of cancer sub-clonal evolutionary trees.\n\nResultsWe propose a clustering method (phyC) for cancer sub-clonal evolutionary trees, in which sub-groups of the trees are identified based on topology and edge length attributes. For interpretation, we also propose a method for evaluating the diversity of trees in the clusters, which provides insight into the acceleration of sub-clonal expansion. Simulation showed that the proposed method can detect true clusters with sufficient accuracy. Application of the method to actual multi-regional sequencing data of clear cell renal carcinoma and non-small cell lung cancer allowed for the detection of clusters related to cancer type or phenotype.\n\nAvailabilityphyC is implemented with R(>=3.2.2) and is available from https://github.com/ymatts/phyC.\n\nContactymatsui@med.nagoya-u.ac.jp

Bioinformatics

Cancer evolution simulation identifies possible principles underlying intratumor heterogeneity

Cancer arises from accumulation of somatic mutations and accompanying evolutionary selection for growth advantage. During the evolutionary process, an ancestor clone branches into multiple clones, yielding intratumor heterogeneity. However, principles underlying intratumor heterogeneity have been poorly understood. Here, to explore the principles, we built a cellular automaton model, termed the BEP model, which can reproduce the branching cancer evolution in silico. We then extensively searched for conditions leading to high intratumor heterogeneity by performing simulations with various parameter settings on a supercomputer. Our result suggests that multiple driver genes of moderate strength can shape subclonal structures by positive natural selection. Moreover, we found that high mutation rate and a stem cell hierarchy can contribute to extremely high intratumor heterogeneity, which is characterized by fractal patterns, through neutral evolution. Collectively, This study identified the possible principles underlying intratumor heterogeneity, which provide novel insights into the origin of cancer robustness and evolvability.

Cancer Biology