QuantiSNP: an Objective Bayes Hidden-Markov Model to detect and accurately map copy number variation using SNP genotyping data.
QuantiSNP: an Objective Bayes Hidden-Markov Model to detect and accurately map copy number variation using SNP genotyping data.
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DOI：
10.1093/nar/gkm076
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发表时间：
2007
影响因子：
14.9
通讯作者：
Ragoussis J
中科院分区：
文献类型：
--
作者：
Colella S;Yau C;Taylor JM;Mirza G;Butler H;Clouston P;Bassett AS;Seller A;Holmes CC;Ragoussis J
基于阵列的技术已被用于检测人类基因组中的染色体拷贝数变化（非整倍性）。最近的研究发现了许多拷贝数变异（CNV），其中一些是可能导致疾病易感性的常见多态性。我们开发并实验验证了一种新的计算框架（QuantiSNP），用于使用客观贝叶斯隐马尔可夫模型（OB-HMM）从BeadArray™ SNP基因分型数据中检测拷贝数变异区域。目的利用贝叶斯测度在先验数据中设置超参数，并采用一种新的重采样框架将模型校准到一个固定的I型（假阳性）错误率。其他参数通过最大边际似然来设置已知结构的先验训练数据。QuantiSNP提供了状态分类的概率量化，并且相对于现有的分析工具（Beadstudio，Illumina），显著提高了节段性非整倍性鉴定和作图的准确性，如通过断点边界的验证所证明的。QuantiSNP鉴定了新的和经验证的CNV。QuantiSNP是使用BeadArray™ SNP数据开发的，但它可以适用于其他平台，我们相信OB-HMM框架在基因组研究中具有广泛的适用性。总之，QuantiSNP是一种用于高分辨率CNV/非整倍体检测的新算法，可应用于临床遗传学、癌症和疾病关联研究。
Array-based technologies have been used to detect chromosomal copy number changes (aneuploidies) in the human genome. Recent studies identified numerous copy number variants (CNV) and some are common polymorphisms that may contribute to disease susceptibility. We developed, and experimentally validated, a novel computational framework (QuantiSNP) for detecting regions of copy number variation from BeadArray™ SNP genotyping data using an Objective Bayes Hidden-Markov Model (OB-HMM). Objective Bayes measures are used to set certain hyperparameters in the priors using a novel re-sampling framework to calibrate the model to a fixed Type I (false positive) error rate. Other parameters are set via maximum marginal likelihood to prior training data of known structure. QuantiSNP provides probabilistic quantification of state classifications and significantly improves the accuracy of segmental aneuploidy identification and mapping, relative to existing analytical tools (Beadstudio, Illumina), as demonstrated by validation of breakpoint boundaries. QuantiSNP identified both novel and validated CNVs. QuantiSNP was developed using BeadArray™ SNP data but it can be adapted to other platforms and we believe that the OB-HMM framework has widespread applicability in genomic research. In conclusion, QuantiSNP is a novel algorithm for high-resolution CNV/aneuploidy detection with application to clinical genetics, cancer and disease association studies.
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影响因子：
30.8
作者：
Gunderson, KL;Steemers, FJ;Chee, MS
通讯作者：
Chee, MS
影响因子：
5.8
作者：
Marioni, JC;Thorne, NP;Tavaré, S
通讯作者：
Tavaré, S
影响因子：
4
作者：
Rauch, A;Rüschendorf, F;Nürnberg, P
通讯作者：
Nürnberg, P
DOI：
10.1111/j.2517-6161.1977.tb01600.x
发表时间：
1977-01-01
期刊：
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-METHODOLOGICAL
影响因子：
--
作者：
DEMPSTER, AP;LAIRD, NM;RUBIN, DB
通讯作者：
RUBIN, DB
影响因子：
7
作者：
Lucito, R;Healy, J;Wigler, M
通讯作者：
Wigler, M