Transcript of “An integrated encyclopedia of DNA elements in the human genome” ENCODE Project Consortium....
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- An integrated encyclopedia of DNA elements in the human genome
ENCODE Project Consortium. Nature 2012 Sep 6; 489:57-74. Michael M.
Hoffman University of Washington 12 September 2012
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- Major results 80% of genome shows biochemical activity ENCODE
elements under purifying selection We can predict RNA using
chromatin data Segmentation of genome into labels Noncoding
variants often in ENCODE elements Disease phenotypes from GWAS can
be associated with a cell type or transcription factor
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- Biochemical activity The vast majority (80.4%) of the human
genome participates in at least one biochemical RNA- and/or
chromatin-associated event in at least one cell type. Much of the
genome lies close to a regulatory event: 95% of the genome lies
within 8 kilobases (kb) of a DNAprotein interaction (as assayed by
bound ChIP-seq motifs or DNase I footprints), and 99% is within 1.7
kb of at least one of the biochemical events measured by
ENCODE.
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- Elements show negative selection Primate-specific elements as
well as elements without detectable mammalian constraint show, in
aggregate, evidence of negative selection; thus, some of them are
expected to be functional.
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- Impact of selection on ENCODE functional elements in mammals
and human populations
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- We can predict RNA expression It is possible to correlate
quantitatively RNA sequence production and processing with both
chromatin marks and transcription factor binding at promoters,
indicating that promoter functionality can explain most of the
variation in RNA expression.
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- Modelling transcription levels from histone modification and
transcription-factor-binding patterns
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- Patterns and asymmetry of chromatin modification at
transcription-factor-binding sites
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- Co-association between transcription factors
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- Genomic segmentation Classifying the genome into seven
chromatin states indicates an initial set of 399,124 regions with
enhancer-like features and 70,292 regions with promoter-like
features, as well as hundreds of thousands of quiescent regions.
High-resolution analyses further subdivide the genome into
thousands of narrow states with distinct functional
properties.
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- Integration of ENCODE data by genome-wide segmentation
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- Experimental characterization of segmentations
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- High-resolution segmentation of ENCODE data by self-organizing
maps (SOM)
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- Non-coding variant annotation Many non-coding variants in
individual genome sequences lie in ENCODE-annotated functional
regions; this number is at least as large as those that lie in
protein-coding genes.
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- Allele-specific ENCODE elements
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- Examining ENCODE elements on a per individual basis in the
normal and cancer genome.
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- GWAS disease SNPs and ENCODE elements Single nucleotide
polymorphisms (SNPs) associated with disease by GWAS are enriched
within non-coding functional elements, with a majority residing in
or near ENCODE-defined regions that are outside of protein-coding
genes. In many cases, the disease phenotypes can be associated with
a specific cell type or transcription factor.
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- Examining ENCODE elements on a per individual basis in the
normal and cancer genome.
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- Major results 80% of genome shows biochemical activity ENCODE
elements under purifying selection We can predict RNA using
chromatin data Segmentation of genome into labels Noncoding
variants often in ENCODE elements Disease phenotypes from GWAS can
be associated with a cell type or transcription factor