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Although there have been computational methods for predicting gene expression from genomic and epigenomic information, most of them neglect long-range enhancer\u2013promoter interactions, due to the difficulty in precisely linking regulatory enhancers to target genes. Recently, HiChIP, a novel high-throughput experimental approach, has generated comprehensive data on high-resolution interactions between promoters and distal enhancers. Moreover, plenty of studies suggest that deep learning achieves state-of-the-art performance in epigenomic signal prediction, and thus promoting the understanding of regulatory elements. In consideration of these two factors, we integrate proximal promoter sequences and HiChIP distal enhancer\u2013promoter interactions to accurately predict gene expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We propose DeepExpression, a densely connected convolutional neural network, to predict gene expression using both promoter sequences and enhancer\u2013promoter interactions. We demonstrate that our model consistently outperforms baseline methods, not only in the classification of binary gene expression status but also in regression of continuous gene expression levels, in both cross-validation experiments and cross-cell line predictions. We show that the sequential promoter information is more informative than the experimental enhancer information; meanwhile, the enhancer\u2013promoter interactions within \u00b1100 kbp around the TSS of a gene are most beneficial. We finally visualize motifs in both promoter and enhancer regions and show the match of identified sequence signatures with known motifs. We expect to see a wide spectrum of applications using HiChIP data in deciphering the mechanism of gene regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>DeepExpression is freely available at https:\/\/github.com\/wanwenzeng\/DeepExpression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btz562","type":"journal-article","created":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T07:09:23Z","timestamp":1563260963000},"page":"496-503","source":"Crossref","is-referenced-by-count":40,"title":["Integrating distal and proximal information to predict gene expression via a densely connected convolutional neural network"],"prefix":"10.1093","volume":"36","author":[{"given":"Wanwen","family":"Zeng","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics , Beijing National Research Center for Information Science and Technology, Department of Automation, Tsinghua University, Beijing 100084, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[{"name":"CEMS, NCMIS, MDIS, Academy of Mathematics and Systems Science , National Center for Mathematics and Interdisciplinary Sciences, Chinese Academy of Sciences, Beijing 100080, China"},{"name":"Center for Excellence in Animal Evolution and Genetics , Chinese Academy of Sciences, Kunming 650223, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Jiang","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics , Beijing National Research Center for Information Science and Technology, Department of Automation, Tsinghua University, Beijing 100084, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,7,18]]},"reference":[{"key":"2023013112080174100_btz562-B1","doi-asserted-by":"crossref","first-page":"831+","DOI":"10.1038\/nbt.3300","article-title":"Predicting the sequence specificities of DNA- and RNA-binding proteins by deep learning","volume":"33","author":"Alipanahi","year":"2015","journal-title":"Nat. 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