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用于DNA拷贝数和基因表达数据联合分析的双层混合模型。

A double-layered mixture model for the joint analysis of DNA copy number and gene expression data.

作者信息

Choi Hyungwon, Qin Zhaohui S, Ghosh Debashis

机构信息

Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.

出版信息

J Comput Biol. 2010 Feb;17(2):121-37. doi: 10.1089/cmb.2009.0019.


DOI:10.1089/cmb.2009.0019
PMID:20170400
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3148827/
Abstract

Copy number aberration is a common form of genomic instability in cancer. Gene expression is closely tied to cytogenetic events by the central dogma of molecular biology, and serves as a mediator of copy number changes in disease phenotypes. Accordingly, it is of interest to develop proper statistical methods for jointly analyzing copy number and gene expression data. This work describes a novel Bayesian inferential approach for a double-layered mixture model (DLMM) which directly models the stochastic nature of copy number data and identifies abnormally expressed genes due to aberrant copy number. Simulation studies were conducted to illustrate the robustness of DLMM under various settings of copy number aberration frequency, confounding effects, and signal-to-noise ratio in gene expression data. Analysis of a real breast cancer data shows that DLMM is able to identify expression changes specifically attributable to copy number aberration in tumors and that a sample-specific index built based on the selected genes is correlated with relevant clinical information.

摘要

拷贝数畸变是癌症中基因组不稳定的一种常见形式。根据分子生物学的中心法则,基因表达与细胞遗传学事件密切相关,并在疾病表型中作为拷贝数变化的介导因素。因此,开发合适的统计方法来联合分析拷贝数和基因表达数据具有重要意义。这项工作描述了一种针对双层混合模型(DLMM)的新型贝叶斯推断方法,该模型直接对拷贝数数据的随机性质进行建模,并识别由于异常拷贝数导致的异常表达基因。进行了模拟研究以说明DLMM在拷贝数畸变频率、混杂效应和基因表达数据信噪比的各种设置下的稳健性。对真实乳腺癌数据的分析表明,DLMM能够识别肿瘤中特别归因于拷贝数畸变的表达变化,并且基于所选基因构建的样本特异性指数与相关临床信息相关。

相似文献

[1]
A double-layered mixture model for the joint analysis of DNA copy number and gene expression data.

J Comput Biol. 2010-2

[2]
Jointly analyzing gene expression and copy number data in breast cancer using data reduction models.

IEEE/ACM Trans Comput Biol Bioinform. 2006

[3]
High-Resolution Genomic Profiling of Disseminated Tumor Cells in Prostate Cancer.

J Mol Diagn. 2016-1

[4]
Detecting copy number status and uncovering subclonal markers in heterogeneous tumor biopsies.

BMC Genomics. 2011-5-11

[5]
CMDS: a population-based method for identifying recurrent DNA copy number aberrations in cancer from high-resolution data.

Bioinformatics. 2009-12-23

[6]
Stochastic segmentation models for array-based comparative genomic hybridization data analysis.

Biostatistics. 2008-4

[7]
Breast tumor copy number aberration phenotypes and genomic instability.

BMC Cancer. 2006-4-18

[8]
Array comparative genomic hybridization copy number profiling: a new tool for translational research in solid malignancies.

Semin Radiat Oncol. 2008-4

[9]
Nonparametric testing for DNA copy number induced differential mRNA gene expression.

Biometrics. 2009-3

[10]
A segmental maximum a posteriori approach to genome-wide copy number profiling.

Bioinformatics. 2008-3-15

引用本文的文献

[1]
CiberAMP: An Package to Identify Differential mRNA Expression Linked to Somatic Copy Number Variations in Cancer Datasets.

Biology (Basel). 2022-9-28

[2]
Bayesian variable selection with graphical structure learning: Applications in integrative genomics.

PLoS One. 2018-7-30

[3]
Characterizing Cancer-Specific Networks by Integrating TCGA Data.

Cancer Inform. 2015-11-23

[4]
Integrative phenotyping framework (iPF): integrative clustering of multiple omics data identifies novel lung disease subphenotypes.

BMC Genomics. 2015-11-11

[5]
A hidden Markov random field-based Bayesian method for the detection of long-range chromosomal interactions in Hi-C data.

Bioinformatics. 2016-3-1

[6]
A Bayesian Graphical Model for Integrative Analysis of TCGA Data.

IEEE Int Workshop Genomic Signal Process Stat. 2012-12

[7]
A HIERARCHICAL BAYESIAN MODEL FOR INFERENCE OF COPY NUMBER VARIANTS AND THEIR ASSOCIATION TO GENE EXPRESSION.

Ann Appl Stat. 2014-3-1

[8]
Detection of candidate tumor driver genes using a fully integrated Bayesian approach.

Stat Med. 2013-12-18

[9]
Bayesian mixture models for assessment of gene differential behaviour and prediction of pCR through the integration of copy number and gene expression data.

PLoS One. 2013-7-12

[10]
Genome-wide identification of significant aberrations in cancer genome.

BMC Genomics. 2012-7-27

本文引用的文献

[1]
Nonparametric testing for DNA copy number induced differential mRNA gene expression.

Biometrics. 2009-3

[2]
Computational methods for the analysis of array comparative genomic hybridization.

Cancer Inform. 2007-2-10

[3]
A segmentation/clustering model for the analysis of array CGH data.

Biometrics. 2007-9

[4]
Integrative analysis of genomic aberrations associated with prostate cancer progression.

Cancer Res. 2007-9-1

[5]
Flexible and accurate detection of genomic copy-number changes from aCGH.

PLoS Comput Biol. 2007-6

[6]
A modified Bayes information criterion with applications to the analysis of comparative genomic hybridization data.

Biometrics. 2007-3

[7]
Continuous-index hidden Markov modelling of array CGH copy number data.

Bioinformatics. 2007-4-15

[8]
Relative impact of nucleotide and copy number variation on gene expression phenotypes.

Science. 2007-2-9

[9]
CGHcall: calling aberrations for array CGH tumor profiles.

Bioinformatics. 2007-4-1

[10]
Global variation in copy number in the human genome.

Nature. 2006-11-23

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