Single-cell copy number variation detection 英文参考文献.docVIP

Chengetal.GenomeBiology2011,12:R80 /content/12/8/R80 METHOD OpenAccess Single-cellcopynumbervariationdetection JiqiuCheng1,2,EvelyneVanneste3,PeterKonings1,2,ThierryVoet3,JorisRVermeesch3andYvesMoreau1,2* Abstract Detectionofchromosomalaberrationsfromasinglecellbyarraycomparativegenomichybridization(single-cell arrayCGH),insteadoffromapopulationofcells,isanemergingtechnique.However,suchdetectionischallenging becauseofthegenomeartifactsandtheDNAamplificationprocessinherenttothesinglecellapproach.Current normalizationalgorithmsresultininaccurateaberrationdetectionforsingle-celldata.Weproposeanormalization methodbasedonchannel,genomecompositionandrecurrentgenomeartifactcorrections.Wedemonstratethat theproposedchannelclonenormalizationsignificantlyimprovesthecopynumbervariationdetectioninboth simulatedandrealsingle-cellarrayCGHdata. Background CGHnormaliter have been developed for array CGH Array analysis of single-cell copy number variations data [10,11]. Poplowess attempts to separate normal (CNVs) is arecently developed experimental technique from aberrant probes using k-means clustering and for the detection of chromosomal rearrangements in applies the loess normalization based on the largest single cells [1-4]. Two-color single-cell array compara- group of probes, whereas CGHnormaliter combines a tive genomic hybridization (CGH) assays the copy segmentation algorithm with loess normalization itera- number difference between an euploid reference sam- tively andnormalizes data based onsegmented normal ple from genomic DNA and an unknown test sample probes. Although these two methods are supposed to from amplified single-cell DNA by comparing signal helpcorrectly recognize real chromosomal aberrations, intensities using log2 ratios [5]. However, the accurate theyarenotabletocorrectgenomeartifacts andcould detection of single-cell CNV has been hampered by result in false calling of aberrations. Alternatively, the the noise levels in the log2 ratios caused