Moduli Spaces of Phylogenetic Trees Describing Tumor Evolutionary Patterns
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- Zairis S., Khiabanian H., Blumberg A.J., Rabadan R. (2014) Moduli Spaces of Phylogenetic Trees Describing Tumor Evolutionary Patterns. In: Ślȩzak D., Tan AH., Peters J.F., Schwabe L. (eds) Brain Informatics and Health. BIH 2014. Lecture Notes in Computer Science, vol 8609. Springer, Cham
Cancers follow a clonal Darwinian evolution, with fitter subclones replacing more quiescent cells, ultimately giving rise to macroscopic disease. High-throughput genomics provides the opportunity to investigate these processes and determine specific genetic alterations driving disease progression. Genomic sampling of a patient’s cancer provides a molecular history, represented by a phylogenetic tree. Cohorts of patients represent a forest of related phylogenetic structures. To extract clinically relevant information, one must represent and statistically compare these collections of trees. We propose a framework based on an application of the work by Billera, Holmes and Vogtmann on phylogenetic tree spaces to the case of unrooted trees of intra-individual cancer tissue samples. We observe that these tree spaces are globally nonpositively curved, allowing for statistical inference on populations of patient histories. A projective tree space is introduced, permitting visualizations of evolutionary patterns. Published data from four types of human malignancies are explored within our framework.
Keywordsphylogenetic tree moduli space tumor evolution genomics
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