Analysis of gene copy number changes in tumor phylogenetics.
BACKGROUND
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.


CONCLUSIONS
The methods introduced here are able to provide more parsimony phylogenies compared to earlier ones which are consider better choices.
School of Computer Science and Technology, Tianjin University, Tianjin, 300072 China ; Department of Computer Science and Engineering, University of South Carolina, Columbia, SC 29208 USA.
Jun
J
Zhou
Research School of Computer Science, Australian National University, Canberra, ACT 0200 Australia.
Yu
Y
Lin
Xerox Research Centre India (XRCI), Bangalore, India.
Vaibhav
V
Rajan
Department of Computer Science and Engineering, University of South Carolina, Columbia, SC 29208 USA.
William
W
Hoskins
Department of Computer Science and Engineering, University of South Carolina, Columbia, SC 29208 USA.
Bing
B
Feng
Department of Computer Science and Engineering, University of South Carolina, Columbia, SC 29208 USA.
Jijun
J
Tang
Chromosomal duplication; FISH; Gene copy number; Gene duplication; Maximum parsimony; Rectilinear Steiner minimum tree; Tumor phylogeny; Whole genome duplication
BMC Cancer. 2007 Dec 18;7:226
18088415
Nat Rev Genet. 2012 Nov;13(11):795-806
23044827
Cancer Res. 2012 Oct 1;72(19):4875-82
23002210
Nature. 2010 Jan 14;463(7278):191-6
20016485
Mol Cell. 2012 Aug 24;47(4):497-510
22920291
Genetics. 2014 Apr;196(4):985-99
24424777
Genome Res. 2010 Jan;20(1):68-80
19903760
Biostatistics. 2004 Oct;5(4):545-56
15475418
Genome Inform Ser Workshop Genome Inform. 1997;8:25-34
11072302
Genome Res. 2012 Feb;22(2):346-61
21994251
PLoS Comput Biol. 2014 Jul 31;10(7):e1003740
25078894
Nat Rev Cancer. 2004 Mar;4(3):177-83
14993899
J Mol Evol. 1976 Mar 29;7(2):133-49
772222
Bioinformatics. 2013 Jul 01;29(13):i189-98
23812984
Nat Rev Mol Cell Biol. 2012 Feb 23;13(3):141-52
22358330
Algorithms Mol Biol. 2012 Aug 29;7(1):21
22931958
Cladistics. 2006 Dec;22(6):589-601
34892898
Ann N Y Acad Sci. 2009 Jun;1168:23-51
19566702
Bull Math Biol. 1987;49(4):461-7
3664032
Bioinformatics. 2009 Nov 1;25(21):2809-15
19692554
Am J Pathol. 2009 Dec;175(6):2637-45
19893027
Evol Bioinform Online. 2007 Nov 12;3:341-56
19461977
Cell. 2012 Mar 2;148(5):886-95
22385958
Proc Natl Acad Sci U S A. 1982 Jul;79(14):4381-5
6812046
Nat Genet. 2013 Oct;45(10):1134-40
24071852
IEEE/ACM Trans Comput Biol Bioinform. 2014 Jul-Aug;11(4):667-72
26356337
Cancer Discov. 2012 Jun;2(6):503-11
22628410
J Bioinform Comput Biol. 2007 Apr;5(2a):407-27
17589968
PLoS Comput Biol. 2012 Jan;8(1):e1002337
22241976
Cell. 2013 Jan 31;152(3):394-405
23374337
Genome Med. 2009 Jun 16;1(6):62
19566914
Nature. 2012 Jan 18;481(7381):306-13
22258609