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Comment
. 2018 Dec;50(12):1630-1633.
doi: 10.1038/s41588-018-0258-x.

Neutral Tumor Evolution?

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Neutral Tumor Evolution?

Maxime Tarabichi et al. Nat Genet. .
Free PMC article

Conflict of interest statement

Competing interest

The authors declare no competing interests.

Figures

Figure 1
Figure 1
(a) Neutrality calls in simulations of tumor growth with subclonal expansion underlying selective sweeps. The tree topology being modelled is represented on the right together with the parameters of the neutral evolution equations for the two subpopulations of cells (Supplementary Methods). The subclone’s fraction (subclone %) increases with its selective advantage advsubclone. We vary the λ = 1 + advsubclone and µ parameters of the subclone along a grid. Simulations are defined as true non-neutral (light blue) or false neutral (dark blue) when the growing subclone has expanded sufficiently to be detectable and the sweep is not complete, i.e. 10% ≤ subclone % ≤ 90%, otherwise the subclone is considered beyond detection (light green). Non-neutral call: R2 < 0.98; neutral call: R2 ≥ 0.98. (b) As (a), using the Gillespie algorithm to simulate branching processes. Simulations leading to subclones beyond detection are either called neutral (light green) or non-neutral (dark green). Because of the stochastic nature of branching processes, different subclone % values are obtained across simulations from the same advsubclone values. For five increasing advsubclone values, we report median ± mad of the subclone % across the simulations. (c) Summary ROC curve for the neutral vs. non-neutral classification based on the R2 values in 1,919 non-neutral simulations from (b), and 1,919 simulations of neutral tumors. The false positive rate and the true positive rate are highlighted for R2 = 0.98 used by Williams et al. (d) dN/dS analysis. Maximum likelihood estimates of the dN/dS ratios and associated 95% confidence intervals for (sub)clonal mutations in TCGA tumors categorized into neutral and non-neutral groups. Ratios for missense and truncating mutations are given. dN/dS > 1 indicates positive selection.

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  • Reply to 'Neutral tumor evolution?'.
    Heide T, Zapata L, Williams MJ, Werner B, Caravagna G, Barnes CP, Graham TA, Sottoriva A. Heide T, et al. Nat Genet. 2018 Dec;50(12):1633-1637. doi: 10.1038/s41588-018-0256-z. Nat Genet. 2018. PMID: 30374073 No abstract available.

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