Estimation of Parent Specific DNA Copy Number in Tumors using High-Density Genotyping Arrays 英文参考文献.docVIP

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Estimation of Parent Specific DNA Copy Number in Tumors using High-Density Genotyping Arrays 英文参考文献.doc

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Estimation of Parent Specific DNA Copy Number in Tumors using High-Density Genotyping Arrays 英文参考文献

EstimationofParentSpecificDNACopyNumberin TumorsusingHigh-DensityGenotypingArrays HaoChen1,HaipengXing2,NancyR.Zhang3* 1DepartmentofStatistics,StanfordUniversity,Stanford,California,UnitedStatesofAmerica,2DepartmentofAppliedMathematicsandStatistics,SUNYatStonyBrook, StonyBrook,NewYork,UnitedStatesofAmerica,3DepartmentofStatistics,StanfordUniversity,Stanford,California,UnitedStatesofAmerica Abstract Chromosomalgainsandlossescompriseanimportanttypeofgeneticchangeintumors,andcannowbeassayedusing 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,forquantifyingnormalcellcontamination,andforgivingamorecompletemolecularportraitofthetumor.We proposeastochasticsegmentationmodelforparent-specificDNAcopynumberintumorsamples,andgiveanestimation procedurethatiscomputationallyefficientandcanbeappliedtodatafromthecurrenthighdensitygenotypingplatforms. 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 fromtheCancerGenomeAtlas(TCGA)project,givingamorecomprehensivesummaryofthecopynumbereventsinthese samples.Detailedcasestudiesonthesesamplesrevealtheadditionalinsightsthatcanbegainedfromanallele-specific copy number analysis, such as the quantification of fractional gains andlosses, the identification of copy neutral loss of heterozygosity,andthecharacterizationofregionsofsimultaneouschangesofbothinheritedchromosomes. Citation:ChenH,XingH,ZhangNR(2011)EstimationofParentSpecificDNACopyNumberinTumorsusingHigh-DensityGenotypingArrays.PLoSComput Biol7(1):e1001060.doi:10.1371/journal.pcbi.1001060 Editor:ScottMarkel,Accelr