Similarity of position frequency matrices for transcription factor binding sites

Similarity of position frequency matrices for transcription factor binding sites
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DOI:
10.1093/bioinformatics/bth480
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发表时间:
2005-02-01
期刊:
影响因子:
5.8
通讯作者:
Zhang, MQ
Zhang, MQ
中科院分区:
生物学3区
文献类型:
--
作者:
Schones, DE;Sumazin, P;Zhang, MQ

文献摘要

被引文献

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动机:高等真核生物启动子序列中的转录因子结合位点(TFBS)通常使用位置频率矩阵(PFM)建模。比较代表结合位点的PFM的能力对于从头序列基序发现尤其重要,在从头序列基序发现中,需要将推定的基质相互比较以及与已知基质进行比较。提出了一种基于乘积多项式分布的PFM相似性量化方法,证明了它的能力,以确定PFM相似性,并表明它有一个更好的假阳性假阴性比相比,现有的方法。我们将来自两个文库的TFBS频率矩阵分组为矩阵族,并鉴定这些文库共有和独特的矩阵。我们确定了Wasserman和Fickett的Mef-2,Myf,Sp-1,SRF和TEF结合位点的肌肉特异性和非肌肉特异性频率矩阵之间的相似性和差异。我们进一步确定了已知的频率矩阵和矩阵族,这些矩阵与Wasserman和Fickett给出的矩阵非常相似。我们提供的方法和工具,比较和查询库的频率矩阵TFBS。
Motivation: Transcription-factor binding sites (TFBS) in promoter sequences of higher eukaryotes are commonly modeled using position frequency matrices (PFM). The ability to compare PFMs representing binding sites is especially important for de novo sequence motif discovery, where it is desirable to compare putative matrices to one another and to known matrices.Results: We describe a PFM similarity quantification method based on product multinomial distributions, demonstrate its ability to identify PFM similarity and show that it has a better false positive to false negative ratio compared to existing methods.We grouped TFBS frequency matrices from two libraries into matrix families and identified the matrices that are common and unique to these libraries. We identified similarities and differences between the skeletal-muscle-specific and non-muscle-specific frequency matrices for the binding sites of Mef-2, Myf, Sp-1, SRF and TEF of Wasserman and Fickett. We further identified known frequency matrices and matrix families that were strongly similar to the matrices given by Wasserman and Fickett. We provide methodology and tools to compare and query libraries of frequency matrices for TFBSs.