Program in Bioinformatics and Integrative Biology
Biochemistry, Biophysics, and Structural Biology | Bioinformatics | Cell and Developmental Biology | Computational Biology | Genomics | Integrative Biology
Enhancers are distal cis-regulatory elements that modulate gene expression. They are depleted of nucleosomes and enriched in specific histone modifications; thus, calling DNase-seq and histone mark ChIP-seq peaks can predict enhancers. We evaluated nine peak-calling algorithms for predicting enhancers validated by transgenic mouse assays. DNase and H3K27ac peaks were consistently more predictive than H3K4me1/2/3 and H3K9ac peaks. DFilter and Hotspot2 were the best DNase peak callers, while HOMER, MUSIC, MACS2, DFilter and F-seq were the best H3K27ac peak callers. We observed that the differential DNase or H3K27ac signals between two distant tissues increased the area under the precision-recall curve (PR-AUC) of DNase peaks by 17.5-166.7% and that of H3K27ac peaks by 7.1-22.2%. We further improved this differential signal method using multiple contrast tissues. Evaluated using a blind test, the differential H3K27ac signal method substantially improved PR-AUC from 0.48 to 0.75 for predicting heart enhancers. We further validated our approach using postnatal retina and cerebral cortex enhancers identified by massively parallel reporter assays, and observed improvements for both tissues. In summary, we compared nine peak callers and devised a superior method for predicting tissue-specific mouse developmental enhancers by reranking the called peaks.
Genomics, Gene Regulation, Chromatin and Epigenetics
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© The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact firstname.lastname@example.org.
DOI of Published Version
Nucleic Acids Res. 2018 Aug 22. doi: 10.1093/nar/gky753. Link to article on publisher's site
Nucleic acids research
Fu, Shaliu; Wang, Qin; Moore, Jill E.; Purcaro, Michael J.; Pratt, Henry E.; Fan, Kaili; Gu, Cuihua; Jiang, Cizhong; Zhu, Ruixin; Kundaje, Anshul; Lu, Aiping; and Weng, Zhiping, "Differential analysis of chromatin accessibility and histone modifications for predicting mouse developmental enhancers" (2018). Program in Bioinformatics and Integrative Biology Publications and Presentations. 133.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License