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Predicting chromatin organization using histone marks.

Huang J, Marco E, Pinello L, Yuan GC - Genome Biol. (2015)

Bottom Line: To aid experimental effort and to understand the determinants of long-range chromatin interactions, we have developed a computational model integrating Hi-C and histone mark ChIP-seq data to predict two important features of chromatin organization: chromatin interaction hubs and topologically associated domain (TAD) boundaries.Cell-type specific histone mark information is required for prediction of chromatin interaction hubs but not for TAD boundaries.Our predictions provide a useful guide for the exploration of chromatin organization.

View Article: PubMed Central - PubMed

Affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. jhuang@jimmy.harvard.edu.

ABSTRACT
Genome-wide mapping of three dimensional chromatin organization is an important yet technically challenging task. To aid experimental effort and to understand the determinants of long-range chromatin interactions, we have developed a computational model integrating Hi-C and histone mark ChIP-seq data to predict two important features of chromatin organization: chromatin interaction hubs and topologically associated domain (TAD) boundaries. Our model accurately and robustly predicts these features across datasets and cell types. Cell-type specific histone mark information is required for prediction of chromatin interaction hubs but not for TAD boundaries. Our predictions provide a useful guide for the exploration of chromatin organization.

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Histone mark signatures of hubs. a-j The distribution of 9 histone marks and CTCF around the center of chromatin anchors. In each panel, the curves with different color represent the four chromatin anchor groups shown in Fig. 1, Hubs (red), Median (green), Low (blue) and None (purple). The normalized signal (y-axis) was calculated using the histone mark ChIP-seq signal minus the input signal
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Fig2: Histone mark signatures of hubs. a-j The distribution of 9 histone marks and CTCF around the center of chromatin anchors. In each panel, the curves with different color represent the four chromatin anchor groups shown in Fig. 1, Hubs (red), Median (green), Low (blue) and None (purple). The normalized signal (y-axis) was calculated using the histone mark ChIP-seq signal minus the input signal

Mentions: To characterize the epigenetic determinants of hubs, we examined the spatial patterns of CTCF and 9 histone marks adjacent to each chromatin anchor (Methods) (Fig. 2). The most distinct features were the elevated levels of H3K4me1 and H3K27ac, both are well-known markers for enhancer elements, around the center of the hubs compared to other chromatin anchors. In addition, there were also significant albeit weaker differences among several other histone marks. In order to systematically investigate how well these hubs could be predicted from the combination of multiple histone marks, we built a Bayesian Additive Regression Trees (BART) model to classify chromatin anchors based on histone mark ChIP-seq data alone. BART is a Bayesian "sum-of-trees" model [22], averaging results from an ensemble of regression trees (Fig. 3a). Previous studies have shown that BART is effective in modeling various computational biology problems [23].Fig. 2


Predicting chromatin organization using histone marks.

Huang J, Marco E, Pinello L, Yuan GC - Genome Biol. (2015)

Histone mark signatures of hubs. a-j The distribution of 9 histone marks and CTCF around the center of chromatin anchors. In each panel, the curves with different color represent the four chromatin anchor groups shown in Fig. 1, Hubs (red), Median (green), Low (blue) and None (purple). The normalized signal (y-axis) was calculated using the histone mark ChIP-seq signal minus the input signal
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4549084&req=5

Fig2: Histone mark signatures of hubs. a-j The distribution of 9 histone marks and CTCF around the center of chromatin anchors. In each panel, the curves with different color represent the four chromatin anchor groups shown in Fig. 1, Hubs (red), Median (green), Low (blue) and None (purple). The normalized signal (y-axis) was calculated using the histone mark ChIP-seq signal minus the input signal
Mentions: To characterize the epigenetic determinants of hubs, we examined the spatial patterns of CTCF and 9 histone marks adjacent to each chromatin anchor (Methods) (Fig. 2). The most distinct features were the elevated levels of H3K4me1 and H3K27ac, both are well-known markers for enhancer elements, around the center of the hubs compared to other chromatin anchors. In addition, there were also significant albeit weaker differences among several other histone marks. In order to systematically investigate how well these hubs could be predicted from the combination of multiple histone marks, we built a Bayesian Additive Regression Trees (BART) model to classify chromatin anchors based on histone mark ChIP-seq data alone. BART is a Bayesian "sum-of-trees" model [22], averaging results from an ensemble of regression trees (Fig. 3a). Previous studies have shown that BART is effective in modeling various computational biology problems [23].Fig. 2

Bottom Line: To aid experimental effort and to understand the determinants of long-range chromatin interactions, we have developed a computational model integrating Hi-C and histone mark ChIP-seq data to predict two important features of chromatin organization: chromatin interaction hubs and topologically associated domain (TAD) boundaries.Cell-type specific histone mark information is required for prediction of chromatin interaction hubs but not for TAD boundaries.Our predictions provide a useful guide for the exploration of chromatin organization.

View Article: PubMed Central - PubMed

Affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. jhuang@jimmy.harvard.edu.

ABSTRACT
Genome-wide mapping of three dimensional chromatin organization is an important yet technically challenging task. To aid experimental effort and to understand the determinants of long-range chromatin interactions, we have developed a computational model integrating Hi-C and histone mark ChIP-seq data to predict two important features of chromatin organization: chromatin interaction hubs and topologically associated domain (TAD) boundaries. Our model accurately and robustly predicts these features across datasets and cell types. Cell-type specific histone mark information is required for prediction of chromatin interaction hubs but not for TAD boundaries. Our predictions provide a useful guide for the exploration of chromatin organization.

Show MeSH