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arXiv 1307.7811q-bio.QMcs.CEcs.DS
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利用RNA测序估计转录本表达的一种新的组合方法:限定路径数

A Novel Combinatorial Method for Estimating Transcript Expression with RNA-Seq: Bounding the Number of Paths

Alexandru I. Tomescu, Anna Kuosmanen, Romeo Rizzi, Veli Mäkinen

摘要:

RNA测序技术为基于短片段的转录本鉴定和定量提供了新的高通量方法,近年来引起了人们极大的兴趣。该问题通常由加权拼接图来建模,其节点代表外显子,其边代表外显子的分裂比对。该任务包括找到一些路径,连同他们的表达水平,最佳地解释各种健身功能,如最小平方和下的图的覆盖率。在(Tomescu et al. RECOMB-seq 2013)中,我们证明了在一般的适应度函数下,如果我们允许最优解中的路径数量为多项式有界,则该问题可以通过简化为最小成本流程序在多项式时间内解决。在本文中,我们进一步完善这个问题,要求一个有界数量k的路径,最佳地解释拼接图。为了得到一个实用的工具,我们实现了三种优化和算法,它们在真实数据上的性能比现有的工具Cufflinks,IsoLasso和SLIDE更好,在模拟数据上的性能也比它们相似或更好。我们的工具名为Toggle,可从http://www.cs.helsinki.fi/gsa/traph/获得

英文摘要:

RNA-Seq technology offers new high-throughput ways for transcript identification and quantification based on short reads, and has recently attracted great interest. The problem is usually modeled by a weighted splicing graph whose nodes stand for exons and whose edges stand for split alignments to the exons. The task consists of finding a number of paths, together with their expression levels, which optimally explain the coverages of the graph under various fitness functions, such least sum of squares. In (Tomescu et al. RECOMB-seq 2013) we showed that under general fitness functions, if we allow a polynomially bounded number of paths in an optimal solution, this problem can be solved in polynomial time by a reduction to a min-cost flow program. In this paper we further refine this problem by asking for a bounded number k of paths that optimally explain the splicing graph. This problem becomes NP-hard in the strong sense, but we give a fast combinatorial algorithm based on dynamic programming for it. In order to obtain a practical tool, we implement three optimizations and heuristics, which achieve better performance on real data, and similar or better performance on simulated data, than state-of-the-art tools Cufflinks, IsoLasso and SLIDE. Our tool, called Traph, is available at http://www.cs.helsinki.fi/gsa/traph/

机构、总结、中文摘要均由AI分析而来,可能存在错误,请以论文正文为准。

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