title: Integrated study of copy number states and genotype calls using high-density SNP arrays.
abstract: We propose a statistical framework, named genoCN, to simultaneously dissect copy number states and genotypes using high-density SNP (single nucleotide polymorphism) arrays. There are at least two types of genomic DNA copy number differences: copy number variations (CNVs) and copy number aberrations (CNAs). While CNVs are naturally occurring and inheritable, CNAs are acquired somatic alterations most often observed in tumor tissues only. CNVs tend to be short and more sparsely located in the genome compared with CNAs. GenoCN consists of two components, genoCNV and genoCNA, designed for CNV and CNA studies, respectively. In contrast to most existing methods, genoCN is more flexible in that the model parameters are estimated from the data instead of being decided a priori. GenoCNA also incorporates two important strategies for CNA studies. First, the effects of tissue contamination are explicitly modeled. Second, if SNP arrays are performed for both tumor and normal tissues of one individual, the genotype calls from normal tissue are used to study CNAs in tumor tissue. We evaluated genoCN by applications to 162 HapMap individuals and a brain tumor (glioblastoma) dataset and showed that our method can successfully identify both types of copy number differences and produce high-quality genotype calls.
authors: Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA. wsun@bios.unc.edu
authors: Wei
authors: W
authors: Sun
authors: Fred A
authors: FA
authors: Wright
authors: Zhengzheng
authors: Z
authors: Tang
authors: Silje H
authors: SH
authors: Nordgard
authors: Peter
authors: P
authors: Van Loo
authors: Tianwei
authors: T
authors: Yu
authors: Vessela N
authors: VN
authors: Kristensen
authors: Charles M
authors: CM
authors: Perou
mesh_terms: D000483:Alleles; D001932:Brain Neoplasms / Q000235:genetics; D002869:Chromosome Aberrations; D014644:Genetic Variation; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008390:Markov Chains; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide