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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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Cell-type specificity of predictions. a Comparison of the prediction accuracy of TAD boundaries by using cell-type specific and average histone mark data. The average data were computed based on 8 cell-types other than IMR90. b Comparison of the prediction accuracy of hubs by using cell-type specific and average histone mark data. The average data were computed based on 8 cell-types other than IMR90
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Fig6: Cell-type specificity of predictions. a Comparison of the prediction accuracy of TAD boundaries by using cell-type specific and average histone mark data. The average data were computed based on 8 cell-types other than IMR90. b Comparison of the prediction accuracy of hubs by using cell-type specific and average histone mark data. The average data were computed based on 8 cell-types other than IMR90

Mentions: To test whether cell-type specific histone modification profiles were needed for prediction of TAD boundaries, we obtained ChIP-seq data in 8 other cell types (GM12878, H1HESC, HMEC, HSMM, HUVEC, K562, NHEK, NHLF), and used the average profile as input of the BART model (Methods). Despite the lack of data in IMR90 cells, the prediction performance was almost indistinguishable (Fig 6a), thereby supporting our hypothesis. Similarly, the precision of using the CTCF consensus peaks slightly better than using the IMR90 specific CTCF peaks (Methods, Fig. 5d). This result is consistent with the previous observation that the TAD structure is stable across cell-types [10, 28]. For comparison, we applied a similar analysis to predict the chromatin interaction hubs, and found that the cell-type specific ChIP-seq data was needed to obtain good prediction accuracy (Fig. 6b). Taken together, these results provide new insights into the cell-type specific differences between TAD boundaries and hubs.Fig. 6


Predicting chromatin organization using histone marks.

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

Cell-type specificity of predictions. a Comparison of the prediction accuracy of TAD boundaries by using cell-type specific and average histone mark data. The average data were computed based on 8 cell-types other than IMR90. b Comparison of the prediction accuracy of hubs by using cell-type specific and average histone mark data. The average data were computed based on 8 cell-types other than IMR90
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig6: Cell-type specificity of predictions. a Comparison of the prediction accuracy of TAD boundaries by using cell-type specific and average histone mark data. The average data were computed based on 8 cell-types other than IMR90. b Comparison of the prediction accuracy of hubs by using cell-type specific and average histone mark data. The average data were computed based on 8 cell-types other than IMR90
Mentions: To test whether cell-type specific histone modification profiles were needed for prediction of TAD boundaries, we obtained ChIP-seq data in 8 other cell types (GM12878, H1HESC, HMEC, HSMM, HUVEC, K562, NHEK, NHLF), and used the average profile as input of the BART model (Methods). Despite the lack of data in IMR90 cells, the prediction performance was almost indistinguishable (Fig 6a), thereby supporting our hypothesis. Similarly, the precision of using the CTCF consensus peaks slightly better than using the IMR90 specific CTCF peaks (Methods, Fig. 5d). This result is consistent with the previous observation that the TAD structure is stable across cell-types [10, 28]. For comparison, we applied a similar analysis to predict the chromatin interaction hubs, and found that the cell-type specific ChIP-seq data was needed to obtain good prediction accuracy (Fig. 6b). Taken together, these results provide new insights into the cell-type specific differences between TAD boundaries and hubs.Fig. 6

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