Position-dependent motif characterization using non-negative matrix factorization.

Position-dependent motif characterization using non-negative matrix factorization.
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DOI:
10.1093/bioinformatics/btn526
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发表时间:
2008-12-01
期刊:
Bioinformatics (Oxford, England)
影响因子:
--
通讯作者:
Graber JH
Graber JH
中科院分区:
其他
文献类型:
--
作者:
Hutchins LN;Murphy SM;Singh P;Graber JH

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动机:顺式作用调控元件通常受到序列内容和相对于功能位点(例如剪接或多聚腺苷酸化位点)的定位两者的限制。我们描述了一种基于非负矩阵分解(NMF)的调控基序分析方法。而现有的模式识别算法通常主要集中在序列的内容,我们的方法同时特点定位和序列内容的假定图案。结果:对人工生成序列的测试表明,NMF能忠实地再现测试模体的位置和内容。我们展示了如何残差平方和的变化可以用来给一个强大的估计序列集的图案或模式的数量。我们的分析区分多个基序在序列内容和/或定位中具有显著重叠。最后,我们通过生物学上有趣的数据集的表征来展示NMF方法的使用。具体而言,对来自广泛的高等真核生物的mRNA 3′-加工(切割和聚腺苷酸化)位点的分析揭示了三个元件的保守核心模式。联系方式:joel.graber@ jax.org补充信息:补充数据可在生物信息学在线获得。
Motivation: Cis-acting regulatory elements are frequently constrained by both sequence content and positioning relative to a functional site, such as a splice or polyadenylation site. We describe an approach to regulatory motif analysis based on non-negative matrix factorization (NMF). Whereas existing pattern recognition algorithms commonly focus primarily on sequence content, our method simultaneously characterizes both positioning and sequence content of putative motifs. Results: Tests on artificially generated sequences show that NMF can faithfully reproduce both positioning and content of test motifs. We show how the variation of the residual sum of squares can be used to give a robust estimate of the number of motifs or patterns in a sequence set. Our analysis distinguishes multiple motifs with significant overlap in sequence content and/or positioning. Finally, we demonstrate the use of the NMF approach through characterization of biologically interesting datasets. Specifically, an analysis of mRNA 3′-processing (cleavage and polyadenylation) sites from a broad range of higher eukaryotes reveals a conserved core pattern of three elements. Contact: joel.graber@jax.org Supplementary information: Supplementary data are available at Bioinformatics online.
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