Defining functional DNA elements in the human genome
Manolis Kellis,Barbara J. Wold,Michael Snyder,Bradley E. Bernstein,Anshul Kundaje,Georgi K. Marinov,Lucas D. Ward,Ewan Birney,Gregory E. Crawford,Job Dekker,Ian Dunham,Laura Elnitski,Peggy J. Farnham,Elise A. Feingold,Mark Gerstein,Morgan C. Giddings,David M. Gilbert,Thomas R. Gingeras,Eric D. Green,Roderic Guigó,Tim Hubbard,Jim Kent,Jason D. Lieb,Richard M. Myers,Michael J. Pazin,Bing Ren,John A. Stamatoyannopoulos,Zhiping Weng,Kevin P. White,Ross C. Hardison +29 more
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TLDR
The strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies are reviewed.Abstract:
With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease.read more
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High-Throughput Sequencing Technologies
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Stefan Washietl,Pouya Kheradpour,Jason Ernst,Lucas D. Ward,Irwin Jungreis,Matthew D. Rasmussen,Manolis Kellis +6 more
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The BioGRID interaction database: 2015 update
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TL;DR: The BioGRID architecture has been improved to support a broader range of interaction and post-translational modification types, to allow the representation of more complex multi-gene/protein interactions, to account for cellular phenotypes through structured ontologies, to expedite curation through semi-automated text-mining approaches, and to enhance curation quality control.
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TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Journal ArticleDOI
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Aaron R. Quinlan,Ira M. Hall +1 more
TL;DR: A new software suite for the comparison, manipulation and annotation of genomic features in Browser Extensible Data (BED) and General Feature Format (GFF) format, which allows the user to compare large datasets (e.g. next-generation sequencing data) with both public and custom genome annotation tracks.
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