RT Journal
A1 Zhang, Zhengdong D.
A1 Paccanaro, Alberto
A1 Fu, Yutao
A1 Weissman, Sherman
A1 Weng, Zhiping
A1 Chang, Joseph
A1 Snyder, Michael
A1 Gerstein, Mark B.
T1 Statistical analysis of the genomic distribution and correlation of regulatory elements in the ENCODE regions
JF Genome Research 
JO Genome Research 
YR 2007 
FD June 01 
VO 17 
IS 6 
SP 787 
OP 797 
DO 10.1101/gr.5573107 
UL http://genome.cshlp.org/content/17/6/787.abstract 
AB The comprehensive inventory of functional elements in 44 human genomic regions carried out by the ENCODE Project Consortium enables for the first time a global analysis of the genomic distribution of transcriptional regulatory elements. In this study we developed an intuitive and yet powerful approach to analyze the distribution of regulatory elements found in many different ChIP–chip experiments on a 10∼100-kb scale. First, we focus on the overall chromosomal distribution of regulatory elements in the ENCODE regions and show that it is highly nonuniform. We demonstrate, in fact, that regulatory elements are associated with the location of known genes. Further examination on a local, single-gene scale shows an enrichment of regulatory elements near both transcription start and end sites. Our results indicate that overall these elements are clustered into regulatory rich “islands” and poor “deserts.” Next, we examine how consistent the nonuniform distribution is between different transcription factors. We perform on all the factors a multivariate analysis in the framework of a biplot, which enhances biological signals in the experiments. This groups transcription factors into sequence-specific and sequence-nonspecific clusters. Moreover, with experimental variation carefully controlled, detailed correlations show that the distribution of sites was generally reproducible for a specific factor between different laboratories and microarray platforms. Data sets associated with histone modifications have particularly strong correlations. Finally, we show how the correlations between factors change when only regulatory elements far from the transcription start sites are considered.