Variable structure motifs for transcription factor binding sites.
Variable structure motifs for transcription factor binding sites.
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DOI：
10.1186/1471-2164-11-30
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发表时间：
2010-01-14
期刊：
影响因子：
4.4
通讯作者：
Ott S
中科院分区：
文献类型：
--
作者：
Reid JE;Evans KJ;Dyer N;Wernisch L;Ott S
传统上，DNA-转录因子结合位点（TFBS）的模型基于相对较少的已知实例，并使用位置权重矩阵（PWMs）将其视为固定长度的位点。已经提出了对该模型的各种扩展，其中大多数考虑了结合位点中碱基之间的依赖性。然而，已知一些转录因子表现出一定的灵活性，并以多于一种可能的物理构型与DNA结合。在某些情况下，已知这种变化会影响结合位点的功能。随着ChIP-seq数据量的增加，现在可以研究包含这种灵活性的模型。以前的可变长度模型的工作受到以下限制：专注于使用限制性模型的酵母中特定的锌指蛋白;依赖于手工制作的模型，一次只针对一个转录因子;以及缺乏对实际大小的数据集的评估。我们重新分析了来自TRANSFAC数据库的结合位点，并发现了我们新的可变长度模型提供更好拟合的激励性示例。我们用一种新的基序搜索算法分析了几个ChIP-seq数据集，并将结果与最好的标准PWM查找器之一和最近开发的用于查找可变结构基序的替代方法进行了比较。所有的方法都进行了交叉验证试验。回收了p53、Stat 5a和Stat 5 b的已知可变结构基序。此外，我们的方法恢复了一个新的通用版本的现有PWM的Sp1，允许可变长度的绑定。该主题提高了分类性能。我们已经提出了一个新的缺口PWM模型的可变长度的DNA结合位点，是不是太多的限制，也没有过度参数化。我们与现有工具的比较表明，平均而言，它没有比现有方法更好的预测准确性。然而，它确实提供了更多的可变结构模体的解释模型，适合后续的结构研究。据我们所知，我们是第一个将可变长度基序模型应用于真核ChIP-seq数据集的人，因此也是第一个显示其在该领域价值的人。这些结果包括一个新的普遍存在的转录因子Sp1的基序。
Classically, models of DNA-transcription factor binding sites (TFBSs) have been based on relatively few known instances and have treated them as sites of fixed length using position weight matrices (PWMs). Various extensions to this model have been proposed, most of which take account of dependencies between the bases in the binding sites. However, some transcription factors are known to exhibit some flexibility and bind to DNA in more than one possible physical configuration. In some cases this variation is known to affect the function of binding sites. With the increasing volume of ChIP-seq data available it is now possible to investigate models that incorporate this flexibility. Previous work on variable length models has been constrained by: a focus on specific zinc finger proteins in yeast using restrictive models; a reliance on hand-crafted models for just one transcription factor at a time; and a lack of evaluation on realistically sized data sets. We re-analysed binding sites from the TRANSFAC database and found motivating examples where our new variable length model provides a better fit. We analysed several ChIP-seq data sets with a novel motif search algorithm and compared the results to one of the best standard PWM finders and a recently developed alternative method for finding motifs of variable structure. All the methods performed comparably in held-out cross validation tests. Known motifs of variable structure were recovered for p53, Stat5a and Stat5b. In addition our method recovered a novel generalised version of an existing PWM for Sp1 that allows for variable length binding. This motif improved classification performance. We have presented a new gapped PWM model for variable length DNA binding sites that is not too restrictive nor over-parameterised. Our comparison with existing tools shows that on average it does not have better predictive accuracy than existing methods. However, it does provide more interpretable models of motifs of variable structure that are suitable for follow-up structural studies. To our knowledge, we are the first to apply variable length motif models to eukaryotic ChIP-seq data sets and consequently the first to show their value in this domain. The results include a novel motif for the ubiquitous transcription factor Sp1.
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发现具有任意插入和删除的序列基序。
影响因子：
4.3
作者：
Frith, Martin C.;Saunders, Neil F. W.;Kobe, Bostjan;Bailey, Timothy L.
通讯作者：
Bailey, Timothy L.
影响因子：
4.3
作者：
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通讯作者：
Yakhini Z
影响因子：
14.8
作者：
Berger, Michael F.;Bulyk, Martha L.
通讯作者：
Bulyk, Martha L.
DOI：
10.1126/science.1162327
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badis G;Berger MF;Philippakis AA;Talukder S;Gehrke AR;Jaeger SA;Chan ET;Metzler G;Vedenko A;Chen X;Kuznetsov H;Wang CF;Coburn D;Newburger DE;Morris Q;Hughes TR;Bulyk ML
通讯作者：
Bulyk ML
影响因子：
64.5
作者：
Cawley, S;Bekiranov, S;Gingeras, TR
通讯作者：
Gingeras, TR