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FISHtrees 3.0: Tumor Phylogenetics Using a Ploidy Probe
E Michael Gertz1, Salim Akhter Chowdhury2,3, Woei-Jyh Lee1
1Computational Biology Branch, National Center for Biotechnology Information, U.S. National Institutes of Health, Bethesda, MD, United States of America.
Plos One
|July 1, 2016
Summary
FISH trees 3.0 models tumor evolution using ploidy and copy-number changes. This approach reveals insights into tumor progression and heterogeneity, aiding in understanding cancer development.
Area of Science:
- Oncology
- Genetics
- Bioinformatics
Background:
- Intra-tumor heterogeneity is a significant challenge in cancer research.
- Fluorescence in situ hybridization (FISH) enables detection of copy-number alterations in solid tumors.
- Tumor evolution can be modeled using phylogenetic trees, incorporating ploidy and gene copy-number variations.
Purpose of the Study:
- To introduce FISHtrees 3.0, a novel computational tool for modeling tumor evolution.
- To implement a ploidy-based tree-building method using mixed integer linear programming (MILP).
- To develop a method for constructing consensus graphs to compare tumor progression across multiple samples.
Main Methods:
- FISH analysis to assess copy-number changes and ploidy in tumor cells.
- Development of a MILP-based algorithm for constructing phylogenetic trees incorporating ploidy.
- Implementation of a consensus graph method for multi-sample tumor progression analysis.
- Validation using simulated data and real-world FISH data from cervical and breast cancer cases.
Main Results:
- FISHtrees 3.0 accurately models tumor evolution, outperforming ploidy-less methods on simulated data.
- Analysis of cervical and breast cancer data revealed significant tumor heterogeneity and divergence.
- DCIS (ductal carcinoma in situ) samples exhibited less complex evolutionary trees than paired IDC (invasive ductal carcinoma) samples.
- Low consensus between DCIS and IDC trees suggests challenges in predicting progression risk.
Conclusions:
- FISHtrees 3.0 provides a robust framework for analyzing tumor evolution and heterogeneity.
- Ploidy-based modeling offers novel insights into cancer progression dynamics.
- The findings highlight the complexity of tumor evolution and may inform biomarker discovery for DCIS progression.
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