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Fast Approximate Inference of Transcript Expression Levels from RNA-seq Data

机译:RNa-seq转录表达水平的快速近似推断   数据

摘要

Motivation: The mapping of RNA-seq reads to their transcripts of origin is afundamental task in transcript expression estimation and differentialexpression scoring. Where ambiguities in mapping exist due to transcriptssharing sequence, e.g. alternative isoforms or alleles, the problem becomes aninstance of non-trivial probabilistic inference. Bayesian inference in such aproblem is intractable and approximate methods must be used such as Markovchain Monte Carlo (MCMC) and Variational Bayes. Standard implementations ofthese methods can be prohibitively slow for large datasets and complex genemodels. Results: We propose an approximate inference scheme based on VariationalBayes applied to an existing model of transcript expression inference fromRNA-seq data. We apply recent advances in Variational Bayes algorithmics toimprove the convergence of the algorithm beyond the standard variationalexpectation-maximisation approach. We apply our algorithm to simulated andbiological datasets, demonstrating that the increase in speed requires only asmall trade-off in accuracy of expression level estimation. Availability: The methods were implemented in R and C++, and are available aspart of the BitSeq project at https://code.google.com/p/bitseq/. The methodswill be made available through the BitSeq Bioconductor package at the nextstable release.
机译:动机:将RNA-seq读段映射到其转录本是转录本表达估计和差异表达评分的基本任务。由于转录本共享序列而在映射中存在歧义的地方,例如替代同工型或等位基因,问题就变成了非平凡概率推断的实例。在这种问题上的贝叶斯推断是难以解决的,必须使用近似方法,例如马尔可夫链蒙特卡罗(MCMC)和变分贝叶斯。对于大型数据集和复杂的基因模型,这些方法的标准实现可能会过慢。结果:我们提出了一个基于VariationalBayes的近似推理方案,该方案适用于现有的基于RNA-seq数据的转录表达推断模型。我们应用变分贝叶斯算法的最新进展来改善算法的收敛性,超越标准的变分期望最大化方法。我们将算法应用于模拟的生物数据集,证明了速度的提高仅需要在表达水平估计的准确性上进行小的折衷。可用性:这些方法是用R和C ++实现的,可作为https://code.google.com/p/bitseq/上BitSeq项目的一部分获得。该方法将在下一个稳定版本通过BitSeq Bioconductor软件包提供。

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