Reconstructing robust phylogenies of metastatic cancers

J. Reiter, A. Makohon-Moore, J. Gerold, I. Bozic, K. Chatterjee, C. Iacobuzio-Donahue, B. Vogelstein, M. Nowak, Reconstructing Robust Phylogenies of Metastatic Cancers, IST Austria, 2015.

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Technical Report | Published | English
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IST Austria Technical Report
Abstract
A comprehensive understanding of the clonal evolution of cancer is critical for understanding neoplasia. Genome-wide sequencing data enables evolutionary studies at unprecedented depth. However, classical phylogenetic methods often struggle with noisy sequencing data of impure DNA samples and fail to detect subclones that have different evolutionary trajectories. We have developed a tool, called Treeomics, that allows us to reconstruct the phylogeny of a cancer with commonly available sequencing technologies. Using Bayesian inference and Integer Linear Programming, robust phylogenies consistent with the biological processes underlying cancer evolution were obtained for pancreatic, ovarian, and prostate cancers. Furthermore, Treeomics correctly identified sequencing artifacts such as those resulting from low statistical power; nearly 7% of variants were misclassified by conventional statistical methods. These artifacts can skew phylogenies by creating illusory tumor heterogeneity among distinct samples. Importantly, we show that the evolutionary trees generated with Treeomics are mathematically optimal.
Publishing Year
Date Published
2015-12-30
Page
25
ISSN
IST-REx-ID

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Reiter J, Makohon-Moore A, Gerold J, et al. Reconstructing Robust Phylogenies of Metastatic Cancers. IST Austria; 2015. doi:10.15479/AT:IST-2015-399-v1-1
Reiter, J., Makohon-Moore, A., Gerold, J., Bozic, I., Chatterjee, K., Iacobuzio-Donahue, C., … Nowak, M. (2015). Reconstructing robust phylogenies of metastatic cancers. IST Austria. https://doi.org/10.15479/AT:IST-2015-399-v1-1
Reiter, Johannes, Alvin Makohon-Moore, Jeffrey Gerold, Ivana Bozic, Krishnendu Chatterjee, Christine Iacobuzio-Donahue, Bert Vogelstein, and Martin Nowak. Reconstructing Robust Phylogenies of Metastatic Cancers. IST Austria, 2015. https://doi.org/10.15479/AT:IST-2015-399-v1-1.
J. Reiter et al., Reconstructing robust phylogenies of metastatic cancers. IST Austria, 2015.
Reiter J, Makohon-Moore A, Gerold J, Bozic I, Chatterjee K, Iacobuzio-Donahue C, Vogelstein B, Nowak M. 2015. Reconstructing robust phylogenies of metastatic cancers, IST Austria, 25p.
Reiter, Johannes, et al. Reconstructing Robust Phylogenies of Metastatic Cancers. IST Austria, 2015, doi:10.15479/AT:IST-2015-399-v1-1.
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