Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
Bioinformatics. 2013 Sep 15;29(18):2292-9. doi: 10.1093/bioinformatics/btt381. Epub 2013 Jul 2.
Many human genes express multiple transcript isoforms through alternative splicing, which greatly increases diversity of protein function. Although RNA sequencing (RNA-Seq) technologies have been widely used in measuring amounts of transcribed mRNA, accurate estimation of transcript isoform abundances from RNA-Seq data is challenging because reads often map to more than one transcript isoforms or paralogs whose sequences are similar to each other.
We propose a statistical method to estimate transcript isoform abundances from RNA-Seq data. Our method can handle gapped alignments of reads against reference sequences so that it allows insertion or deletion errors within reads. The proposed method optimizes the number of transcript isoforms by variational Bayesian inference through an iterative procedure, and its convergence is guaranteed under a stopping criterion. On simulated datasets, our method outperformed the comparable quantification methods in inferring transcript isoform abundances, and at the same time its rate of convergence was faster than that of the expectation maximization algorithm. We also applied our method to RNA-Seq data of human cell line samples, and showed that our prediction result was more consistent among technical replicates than those of other methods.
An implementation of our method is available at http://github.com/nariai/tigar
Supplementary data are available at Bioinformatics online.
许多人类基因通过选择性剪接表达多种转录本异构体,这极大地增加了蛋白质功能的多样性。尽管 RNA 测序 (RNA-Seq) 技术已广泛用于测量转录 mRNA 的量,但从 RNA-Seq 数据准确估计转录本异构体丰度具有挑战性,因为读取通常映射到多个转录本异构体或彼此序列相似的同源基因。
我们提出了一种从 RNA-Seq 数据估计转录本异构体丰度的统计方法。我们的方法可以处理读取与参考序列的有间隙比对,从而允许读取内的插入或删除错误。所提出的方法通过迭代过程通过变分贝叶斯推断优化转录本异构体的数量,并且在停止准则下保证其收敛性。在模拟数据集上,我们的方法在推断转录本异构体丰度方面优于可比的定量方法,同时其收敛速度快于期望最大化算法。我们还将我们的方法应用于人类细胞系样本的 RNA-Seq 数据,并表明我们的预测结果在技术重复之间比其他方法更一致。
我们的方法的实现可在 http://github.com/nariai/tigar 上获得。
补充数据可在生物信息学在线获得。