Analysis of gene copy number changes in tumor phylogenetics
Date
2016-09-22
Authors
Zhou, Jun
Lin, Yu
Rajan, Vaibhav
Hoskins, William
Feng, Bing
Tang, Jijun
Journal Title
Journal ISSN
Volume Title
Publisher
BioMed Central
Abstract
BACKGOUND Evolution of cancer cells is characterized by large scale and rapid changes in the chromosomal landscape. The fluorescence in situ hybridization (FISH) technique provides a way to measure the copy numbers of preselected genes in a group of cells and has been found to be a reliable source of data to model the evolution of tumor cells. Chowdhury et al. (Bioinformatics 29(13):189-98, 23; PLoS Comput Biol 10(7):1003740, 24) recently develop a computational model for tumor progression driven by gains and losses in cell count patterns obtained by FISH probes. Their model aims to find the rectilinear Steiner minimum tree (RSMT) (Chowdhury et al. in Bioinformatics 29(13):189-98, 23) and the duplication Steiner minimum tree (DSMT) (Chowdhury et al. in PLoS Comput Biol 10(7):1003740, 24) that describe the progression of FISH cell count patterns over its branches in a parsimonious manner. Both the RSMT and DSMT problems are NP-hard and heuristics are required to solve the problems efficiently. METHODS In this paper we propose two approaches to solve the RSMT problem, one inspired by iterative methods to address the "small phylogeny" problem (Sankoff et al. in J Mol Evol 7(2):133-49, 27; Blanchette et al. in Genome Inform 8:25-34, 28), and the other based on maximum parsimony phylogeny inference. We further show how to extend these heuristics to obtain solutions to the DSMT problem, that models large scale duplication events. RESULTS Experimental results from both simulated and real tumor data show that our methods outperform previous heuristics (Chowdhury et al. in Bioinformatics 29(13):189-98, 23; Chowdhury et al. in PLoS Comput Biol 10(7):1003740, 24) in obtaining solutions to both RSMT and DSMT problems. CONCLUSION The methods introduced here are able to provide more parsimony phylogenies compared to earlier ones which are consider better choices.
Description
Keywords
chromosomal duplication, fish, gene copy number, gene duplication, maximum parsimony, rectilinear steiner minimum tree, tumor phylogeny, whole genome duplication
Citation
Collections
Source
Algorithms for molecular biology : AMB
Type
Journal article
Book Title
Entity type
Access Statement
Open Access
License Rights
Restricted until
Downloads
File
Description