A phylogenetic model for understanding the effect of gene duplication on cancer progression
Genre
Journal ArticleDate
2014-03-01Author
Ma, QReeves, JH
Liberles, DA
Yu, L
Chang, Z
Zhao, J
Cui, J
Xu, Y
Liu, L
Subject
Disease ProgressionGene Deletion
Gene Duplication
Genes, Duplicate
Humans
Likelihood Functions
Models, Genetic
Models, Statistical
Phylogeny
Stomach Neoplasms
Permanent link to this record
http://hdl.handle.net/20.500.12613/5348
Metadata
Show full item recordDOI
10.1093/nar/gkt1320Abstract
As biotechnology advances rapidly, a tremendous amount of cancer genetic data has become available, providing an unprecedented opportunity for understanding the genetic mechanisms of cancer. To understand the effects of duplications and deletions on cancer progression, two genomes (normal and tumor) were sequenced from each of five stomach cancer patients in different stages (I, II, III and IV). We developed a phylogenetic model for analyzing stomach cancer data. The model assumes that duplication and deletion occur in accordance with a continuous time Markov Chain along the branches of a phylogenetic tree attached with five extended branches leading to the tumor genomes. Moreover, coalescence times of the phylogenetic tree follow a coalescence process. The simulation study suggests that the maximum likelihood approach can accurately estimate parameters in the phylogenetic model. The phylogenetic model was applied to the stomach cancer data. We found that the expected number of changes (duplication and deletion) per gene for the tumor genomes is significantly higher than that for the normal genomes. The goodness-of-fit test suggests that the phylogenetic model with constant duplication and deletion rates can adequately fit the duplication data for the normal genomes. The analysis found nine duplicated genes that are significantly associated with stomach cancer. © The Author(s) 2013.Citation to related work
Oxford University Press (OUP)Has part
Nucleic Acids ResearchADA compliance
For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.eduae974a485f413a2113503eed53cd6c53
http://dx.doi.org/10.34944/dspace/5330