Estimation of parent specific DNA copy number in tumors using high-density genotyping arrays

Chromosomal gains and losses comprise an important type of genetic change in tumors, and can now be assayed using microarray hybridization-based experiments. Most current statistical models for DNA copy number estimate total copy number, which do not distinguish between the underlying quantities of...

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Bibliographic Details
Published in:PLoS computational biology 2011-01, Vol.7 (1), p.e1001060-e1001060
Main Authors: Chen, Hao, Xing, Haipeng, Zhang, Nancy R
Format: Article
Language:English
Subjects:
Alleles
Analysis
Chromosomes
Computational Biology
Deoxyribonucleic acid
Disease transmission
DNA
DNA, Neoplasm - genetics
Gene Dosage
Genes
Genetic aspects
Genetic variation
Genetics
Genotype
Gliomas
Humans
Markov Chains
Parents
Polymorphism, Single Nucleotide
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Summary:Chromosomal gains and losses comprise an important type of genetic change in tumors, and can now be assayed using microarray hybridization-based experiments. Most current statistical models for DNA copy number estimate total copy number, which do not distinguish between the underlying quantities of the two inherited chromosomes. This latter information, sometimes called parent specific copy number, is important for identifying allele-specific amplifications and deletions, for quantifying normal cell contamination, and for giving a more complete molecular portrait of the tumor. We propose a stochastic segmentation model for parent-specific DNA copy number in tumor samples, and give an estimation procedure that is computationally efficient and can be applied to data from the current high density genotyping platforms. The proposed method does not require matched normal samples, and can estimate the unknown genotypes simultaneously with the parent specific copy number. The new method is used to analyze 223 glioblastoma samples from the Cancer Genome Atlas (TCGA) project, giving a more comprehensive summary of the copy number events in these samples. Detailed case studies on these samples reveal the additional insights that can be gained from an allele-specific copy number analysis, such as the quantification of fractional gains and losses, the identification of copy neutral loss of heterozygosity, and the characterization of regions of simultaneous changes of both inherited chromosomes.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1001060