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Abstract MotivationCancer phylogenies are key to studying tumorigenesis and have clinical implications. Due to the heterogeneous nature of cancer and limitations in current sequencing technology, current cancer phylogeny inference methods identify a large solution space of plausible phylogenies. To facilitate further downstream analyses, methods that accurately summarize such a set T of cancer phylogenies are imperative. However, current summary methods are limited to a single consensus tree or graph and may miss important topological features that are present in different subsets of candidate trees. ResultsWe introduce the Multiple Consensus Tree (MCT) problem to simultaneously cluster T and infer a consensus tree for each cluster. We show that MCT is NP-hard, and present an exact algorithm based on mixed integer linear programming (MILP). In addition, we introduce a heuristic algorithm that efficiently identifies high-quality consensus trees, recovering all optimal solutions identified by the MILP in simulated data at a fraction of the time. We demonstrate the applicability of our methods on both simulated and real data, showing that our approach selects the number of clusters depending on the complexity of the solution space T. Availability and implementationhttps://github.com/elkebir-group/MCT. Supplementary informationSupplementary data are available at Bioinformatics online.
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Identifying simultaneous rearrangements in cancer genomes
Abstract MotivationThe traditional view of cancer evolution states that a cancer genome accumulates a sequential ordering of mutations over a long period of time. However, in recent years it has been suggested that a cancer genome may instead undergo a one-time catastrophic event, such as chromothripsis, where a large number of mutations instead occur simultaneously. A number of potential signatures of chromothripsis have been proposed. In this work, we provide a rigorous formulation and analysis of the ‘ability to walk the derivative chromosome’ signature originally proposed by Korbel and Campbell. In particular, we show that this signature, as originally envisioned, may not always be present in a chromothripsis genome and we provide a precise quantification of under what circumstances it would be present. We also propose a variation on this signature, the H/T alternating fraction, which allows us to overcome some of the limitations of the original signature. ResultsWe apply our measure to both simulated data and a previously analyzed real cancer dataset and find that the H/T alternating fraction may provide useful signal for distinguishing genomes having acquired mutations simultaneously from those acquired in a sequential fashion. Availability and implementationAn implementation of the H/T alternating fraction is available at https://bitbucket.org/oesperlab/ht-altfrac. Supplementary informationSupplementary data are available at Bioinformatics online.
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- Award ID(s):
- 1657380
- PAR ID:
- 10393369
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- Bioinformatics
- Volume:
- 34
- Issue:
- 2
- ISSN:
- 1367-4803
- Page Range / eLocation ID:
- p. 346-352
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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