Benos Panayiotis V, Corcoran David L, Feingold Eleanor
Department of Computational Biology, University of Pittsburgh School of Medicine, USA.
Methods Mol Biol. 2007;395:425-36. doi: 10.1007/978-1-59745-514-5_26.
Transcription regulation on a gene-by-gene basis is achieved through transcription factors, the DNA-binding proteins that recognize short DNA sequences in the proximity of the genes. Unlike other DNA-binding proteins, each transcription factor recognizes a number of sequences, usually variants of a preferred, "consensus" sequence. The degree of dissimilarity of a given target sequence from the consensus is indicative of the binding affinity of the transcription factor-DNA interaction. Because of the short size and the degeneracy of the patterns, it is frequently difficult for a computational algorithm to distinguish between the true sites and the background genomic "noise." One way to overcome this problem of low signal-to-noise ratio is to use evolutionary information to detect signals that are conserved in two or more species. FOOTER is an algorithm that uses this phylogenetic footprinting concept and evaluates putative mammalian transcription factor binding sites in a quantitative way. The user is asked to upload the human and mouse promoter sequences and select the transcription factors to be analyzed. The results' page presents an alignment of the two sequences (color-coded by degree of conservation) and information about the predicted sites and single-nucleotide polymorphisms found around the predicted sites. This chapter presents the main aspects of the underlying method and gives detailed instructions and tips on the use of this web-based tool.
基于逐个基因的转录调控是通过转录因子实现的，转录因子是一类识别基因附近短DNA序列的DNA结合蛋白。与其他DNA结合蛋白不同，每个转录因子能识别多个序列，通常是一个优选的“共有”序列的变体。给定靶序列与共有序列的差异程度表明了转录因子与DNA相互作用的结合亲和力。由于这些模式的长度较短且存在简并性，计算算法常常难以区分真正的位点和背景基因组“噪声”。克服这种低信噪比问题的一种方法是利用进化信息来检测在两个或更多物种中保守的信号。FOOTER是一种利用这种系统发育足迹概念并以定量方式评估假定的哺乳动物转录因子结合位点的算法。用户被要求上传人类和小鼠的启动子序列并选择要分析的转录因子。结果页面呈现了两个序列的比对（根据保守程度进行颜色编码）以及关于预测位点和在预测位点周围发现的单核苷酸多态性的信息。本章介绍了该基础方法的主要方面，并给出了关于使用这个基于网络的工具的详细说明和提示。
