Abstract
We introduce PyClone, a statistical model for inference of clonal population structures in cancers. PyClone is a Bayesian clustering method for grouping sets of deeply sequenced somatic mutations into putative clonal clusters while estimating their cellular prevalences and accounting for allelic imbalances introduced by segmental copy-number changes and normal-cell contamination. Single-cell sequencing validation demonstrates PyClone's accuracy.
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Acknowledgements
This work is funded by Canadian Institutes for Health Research (CIHR), Genome Canada, Genome British Columbia, Canadian Cancer Society Research Institute and Canadian Breast Cancer Foundation grants to S.P.S. and S.A. S.P.S. is supported by the Michael Smith Foundation for Health Research and is the Canada Research Chair (CRC) for Computational Cancer Genomics. S.A. is the CRC for Molecular Oncology. A.R. is supported by a CIHR Banting scholarship.
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Project conception and oversight: S.P.S., S.A., A.R.; method development: A.R., A.B.-C., S.P.S.; implementation and benchmarking: A.R.; manuscript writing and editing, study design and execution: A.R., A.B.C., S.P.S., S.A.; single-cell sequencing: J.K., D.Y., A.W., E.L., J.B.; data analysis and interpretation: G.H.
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Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–14, Supplementary Results, Supplementary Discussion and Supplementary Note (PDF 5370 kb)
Supplementary Table 1
Allelic counts, IBBMM and PyClone PCN cellular prevalence estimates for mutations in high grade serous ovarian cancer case 2. Copy number predictions where inferred using PICNIC as described in the Online Methods. Cellular prevalences where computed by taking the mean of the post burnin trace for the cellular prevalences for the respective methods. The standard deviation of the cellular prevalence parameter estimated from the post burnin trace is also included. Cluster ids (last two columns) were predicted from the post burnin trace using the MPEAR clustering criteria as described in the Online Methods and Supplementary Note. Mutation ids list gene name, chromosome and chromosome coordinate. All coordinates are in the hg19 coordinate system. (XLS 50 kb)
Supplementary Table 2
Allelic counts, IBBMM and PyClone PCN cellular prevalence estimates for mutations in high grade serous ovarian cancer case 1. Copy number predictions where inferred using PICNIC as described in the Online Methods. Cellular prevalences where computed by taking the mean of the post burnin trace for the cellular prevalences for the respective methods. The standard deviation of the cellular prevalence parameter estimated from the post burnin trace is also included. Cluster ids (last two columns) were predicted from the post burnin trace using the MPEAR clustering criteria as described in the Online Methods and Supplementary Note. Mutation ids list gene name, chromosome and chromosome coordinate. All coordinates are in the hg19 coordinate system. (XLSX 40 kb)
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Roth, A., Khattra, J., Yap, D. et al. PyClone: statistical inference of clonal population structure in cancer. Nat Methods 11, 396–398 (2014). https://doi.org/10.1038/nmeth.2883
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DOI: https://doi.org/10.1038/nmeth.2883
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