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2015 ; 25
(4
): 544-57
Nephropedia Template TP
gab.com Text
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English Wikipedia
Joint annotation of chromatin state and chromatin conformation reveals
relationships among domain types and identifies domains of cell-type-specific
expression
#MMPMID25677182
Libbrecht MW
; Ay F
; Hoffman MM
; Gilbert DM
; Bilmes JA
; Noble WS
Genome Res
2015[Apr]; 25
(4
): 544-57
PMID25677182
show ga
The genomic neighborhood of a gene influences its activity, a behavior that is
attributable in part to domain-scale regulation. Previous genomic studies have
identified many types of regulatory domains. However, due to the difficulty of
integrating genomics data sets, the relationships among these domain types are
poorly understood. Semi-automated genome annotation (SAGA) algorithms facilitate
human interpretation of heterogeneous collections of genomics data by
simultaneously partitioning the human genome and assigning labels to the
resulting genomic segments. However, existing SAGA methods cannot integrate
inherently pairwise chromatin conformation data. We developed a new computational
method, called graph-based regularization (GBR), for expressing a pairwise prior
that encourages certain pairs of genomic loci to receive the same label in a
genome annotation. We used GBR to exploit chromatin conformation information
during genome annotation by encouraging positions that are close in 3D to occupy
the same type of domain. Using this approach, we produced a model of chromatin
domains in eight human cell types, thereby revealing the relationships among
known domain types. Through this model, we identified clusters of tightly
regulated genes expressed in only a small number of cell types, which we term
"specific expression domains." We found that domain boundaries marked by
promoters and CTCF motifs are consistent between cell types even when domain
activity changes. Finally, we showed that GBR can be used to transfer information
from well-studied cell types to less well-characterized cell types during genome
annotation, making it possible to produce high-quality annotations of the
hundreds of cell types with limited available data.