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/
Competing endogenous RNA crosstalk at system level
microRNAs(miRNAs)通过抑制靶RNA分子在转录后水平调控基因表达。竞争结合miRNA往往反过来关联它们的靶标,建立有效的RNA-RNA相互作用,可以影响表达水平,缓冲波动并促进信号传播。这样的潜力已经在数学上表征为小图案在稳态和\red{away from stationarity}。另一方面,实验证据表明竞争性内源RNA(ceRNA)串扰相当弱。然而,扩展的miRNA-RNA网络可能有利于许多串扰相互作用的整合,导致显著的大规模效应,尽管单个链接的弱点。为了阐明串扰在多大程度上是由miRNA相互作用组维持的,我们在大规模的miRNA-RNA网络重建中研究了其涌现的系统特征。我们表明,虽然一般弱,系统水平的串扰模式(i)增强了转录异质性,(ii)可以实现高强度,甚至对于RNA,不共调节,(iii)是强大的转录速率的变化,和(iv)是显着的非本地,即弱相关的miRNA-RNA相互作用参数。此外,当串扰最强时,RNA水平一般更稳定。由于这些特征中的一些似乎被编码在网络的拓扑结构中,串扰可能在功能上受到自然选择的青睐。这些结果表明,除了它们的抑制作用外,miRNA还介导了一个弱但有弹性且与上下文无关的交叉调节相互作用网络,该网络将转录组互连,稳定表达水平并支持系统水平的反应。
A polynomial delay algorithm for the enumeration of bubbles with length constraints in directed graphs and its application to the detection of alternative splicing in RNA-seq data