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使用负二项式模型族对RNA测序数据进行贝叶斯分析。

Bayesian Analysis of RNA-Seq Data Using a Family of Negative Binomial Models.

作者信息

Zhao Lili, Wu Weisheng, Feng Dai, Jiang Hui, Nguyen XuanLong

机构信息

Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, U.S.A.

Department of Computational Medicine & Bioinformatics, University of Michigan.

出版信息

Bayesian Anal. 2018 Jun;13(2):411-436. doi: 10.1214/17-BA1055. Epub 2017 Apr 8.

DOI:10.1214/17-BA1055
PMID:33868546
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8052637/
Abstract

The analysis of RNA-Seq data has been focused on three main categories, including gene expression, relative exon usage and transcript expression. Methods have been proposed independently for each category using a negative binomial (NB) model. However, counts following a NB distribution on one feature (e.g., exon) do not guarantee a NB distribution for the other two features (e.g., gene/transcript). In this paper we propose a family of Negative Binomial models, which integrates the gene, exon and transcript analysis under a coherent NB model. The proposed model easily incorporates the uncertainty of assigning reads to transcripts and simplifies substantially the estimation for the relative usage. We developed simple Gibbs sampling algorithms for the posterior inference by exploiting fully tractable closed-forms of computation via suitable conjugate priors. The proposed models were investigated under extensive simulations. Finally, we applied our model to a real data set.

摘要

RNA测序数据的分析主要集中在三个主要类别上,包括基因表达、外显子相对使用情况和转录本表达。针对每个类别,已经独立提出了使用负二项式(NB)模型的方法。然而,一个特征(例如外显子)上遵循NB分布的计数并不能保证其他两个特征(例如基因/转录本)也遵循NB分布。在本文中,我们提出了一族负二项式模型,该模型在一个连贯的NB模型下整合了基因、外显子和转录本分析。所提出的模型很容易纳入将 reads 分配到转录本的不确定性,并大大简化了相对使用情况的估计。我们通过利用合适的共轭先验的完全可处理的封闭形式计算,开发了用于后验推断的简单吉布斯采样算法。在广泛的模拟下对所提出的模型进行了研究。最后,我们将我们的模型应用于一个真实数据集。

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本文引用的文献

1
Negative Binomial Process Count and Mixture Modeling.负二项式过程计数和混合建模。
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2
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2.使用DESeq2对RNA测序数据的倍数变化和离散度进行适度估计。
Genome Biol. 2014;15(12):550. doi: 10.1186/s13059-014-0550-8.
3
IUTA: a tool for effectively detecting differential isoform usage from RNA-Seq data.IUTA:一种从RNA测序数据中有效检测差异异构体使用情况的工具。
BMC Genomics. 2014 Oct 6;15(1):862. doi: 10.1186/1471-2164-15-862.
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ShrinkBayes: a versatile R-package for analysis of count-based sequencing data in complex study designs.ShrinkBayes:一个用于在复杂研究设计中分析基于计数的测序数据的多功能 R 包。
BMC Bioinformatics. 2014 Apr 26;15:116. doi: 10.1186/1471-2105-15-116.
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Statistical Modeling of RNA-Seq Data.RNA测序数据的统计建模
Stat Sci. 2011 Feb;26(1). doi: 10.1214/10-STS343.
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rSeqDiff: detecting differential isoform expression from RNA-Seq data using hierarchical likelihood ratio test.rSeqDiff:使用层次似然比检验从 RNA-Seq 数据中检测差异异构体表达。
PLoS One. 2013 Nov 18;8(11):e79448. doi: 10.1371/journal.pone.0079448. eCollection 2013.
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Comprehensive evaluation of differential gene expression analysis methods for RNA-seq data.RNA测序数据差异基因表达分析方法的综合评估
Genome Biol. 2013;14(9):R95. doi: 10.1186/gb-2013-14-9-r95.
8
TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions.TopHat2:在存在插入、缺失和基因融合的情况下对转录组进行精确比对。
Genome Biol. 2013 Apr 25;14(4):R36. doi: 10.1186/gb-2013-14-4-r36.
9
A comparison of methods for differential expression analysis of RNA-seq data.RNA-seq 数据差异表达分析方法的比较。
BMC Bioinformatics. 2013 Mar 9;14:91. doi: 10.1186/1471-2105-14-91.
10
EBSeq: an empirical Bayes hierarchical model for inference in RNA-seq experiments.EBSeq:RNA-seq 实验中用于推理的经验贝叶斯层次模型。
Bioinformatics. 2013 Apr 15;29(8):1035-43. doi: 10.1093/bioinformatics/btt087. Epub 2013 Feb 21.