Schones Dustin E, Sumazin Pavel, Zhang Michael Q
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Bioinformatics. 2005 Feb 1;21(3):307-13. doi: 10.1093/bioinformatics/bth480. Epub 2004 Aug 19.
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.
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.
Software is available to use over the Web at http://rulai.cshl.edu/MatCompare
Database and clustering statistics, matrix families and representatives are available at http://rulai.cshl.edu/MatCompare/Supplementary.
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）进行建模。比较代表结合位点的PFM的能力对于从头序列基序发现尤为重要，在该过程中，需要将推定的矩阵相互比较以及与已知矩阵进行比较。
我们描述了一种基于乘积多项分布的PFM相似性量化方法，证明了其识别PFM相似性的能力，并表明与现有方法相比，它具有更好的假阳性与假阴性比率。我们将来自两个文库的TFBS频率矩阵分组为矩阵家族，并确定了这些文库共有的和独特的矩阵。我们确定了Wasserman和Fickett的Mef-2、Myf、Sp-1、SRF和TEF结合位点的骨骼肌特异性和非肌肉特异性频率矩阵之间的异同。我们进一步确定了与Wasserman和Fickett给出的矩阵高度相似的已知频率矩阵和矩阵家族。我们提供了用于比较和查询TFBS频率矩阵文库的方法和工具。
可通过网络在http://rulai.cshl.edu/MatCompare上使用该软件。
数据库和聚类统计、矩阵家族和代表可在http://rulai.cshl.edu/MatCompare/Supplementary上获取。
