Wed, 09 Jul 2008 16:02:17 BST CiteULike: dpollards hypersensitive http://www.citeulike.org/user/dpollard/tag/hypersensitive CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/dpollard/article/2318224 <i>Pac Symp Biocomput (2008), pp. 201-215.</i><br /><br />Functional genomic quantities such as histone modifications, chromatin accessibility, and evolutionary constraint can now be measured in a nearly continuous fashion across the genome. The genome is highly heterogeneous, and the relationships between different functional annotations may be fluid. Here we present an approach for visualizing, quantifying, and determining the statistical significance of local and regional correlations between high-density continuous genomic datasets. We use wavelets to generate a multi-scale view of each component data set and calculate correlations between data types as a function of genome position over a continuous range of scales in sliding window fashion. We determine the statistical significance of correlations using a non-parametric sampling approach. We apply the wavelet correlation method to histone modification and chromatin accessibility (DNasel sensitivity) data from the NHGRI ENCODE project. We show that DNaseI sensitivity is broadly correlated (though to differing degrees) with a number of different activating histone modifications. We examine the continuous relationship between the repressive histone modification H3K27me3 and the activating mark H3K4me2, and find these modifications to display significant duality, with both significant positively and negatively correlated genomic territories. While the former appear to recapitulate in definitive cells the so-called "bi-valent" pattern originally proposed as a signature of pluripotency, the presence of negatively correlated regions suggests that the regulatory events that underlie the observed modification patterns are complex and highly regionalized in the genome. Multi-scale correlations in continuous genomic data. RE Thurman WS Noble JA Stamatoyannopoulos Pac Symp Biocomput (2008), pp. 201-215. 2008-02-01T07:04:32-00:00 2008 Pac Symp Biocomput 1793-5091 201 215 correlation histone hypersensitive nucleosome http://www.citeulike.org/user/dpollard/article/878424 <i>Genome Res (8 September 2006)</i><br /><br />The identification of cis-regulatory elements is central to understanding gene transcription. Hypersensitivity of cis-regulatory elements to digestion with DNaseI remains the gold-standard approach to locating such elements. Traditional methods used to identify DNaseI hypersensitive sites are cumbersome and can only be applied to short stretches of DNA at defined locations. Here we report the development of a novel genomic array-based approach to DNaseI hypersensitive site mapping (ADHM) that permits precise, large-scale identification of such sites from as few as 5 million cells. Using ADHM we identified all previously recognized hematopoietic regulatory elements across 200 kb of the mouse T-cell acute lymphocytic leukemia-1 (Tal1) locus, and, in addition, identified two novel elements within the locus, which show transcriptional regulatory activity. We further validated the ADHM protocol by mapping the DNaseI hypersensitive sites across 250 kb of the human TAL1 locus in CD34(+) primary stem/progenitor cells and K562 cells and by mapping the previously known DNaseI hypersensitive sites across 240 kb of the human alpha-globin locus in K562 cells. ADHM provides a powerful approach to identifying DNaseI hypersensitive sites across large genomic regions. Identifying gene regulatory elements by genomic microarray mapping of DNaseI hypersensitive sites. George A Follows Pawan Dhami Berthold Göttgens Alexander W Bruce Peter J Campbell Shane C Dillon Aileen M Smith Christoph Koch Ian J Donaldson Mike A Scott Ian Dunham Mary E Janes David Vetrie Anthony R Green doi:10.1101/gr.5373606 Genome Res (8 September 2006) 2006-09-29T23:25:30-00:00 2006 Genome Res 1088-9051 array dnasei hypersensitive prediction