Title
DeepHINT: Understanding HIV-1 integration via deep learning with attention.
Abstract
Motivation Human immunodeficiency virus type 1 (HIV-1) genome integration is closely related to clinical latency and viral rebound. In addition to human DNA sequences that directly interact with the integration machinery, the selection of HIV integration sites has also been shown to depend on the heterogeneous genomic context around a large region, which greatly hinders the prediction and mechanistic studies of HIV integration. Results We have developed an attention-based deep learning framework, named DeepHINT, to simultaneously provide accurate prediction of HIV integration sites and mechanistic explanations of the detected sites. Extensive tests on a high-density HIV integration site dataset showed that DeepHINT can outperform conventional modeling strategies by automatically learning the genomic context of HIV integration from primary DNA sequence alone or together with epigenetic information. Systematic analyses on diverse known factors of HIV integration further validated the biological relevance of the prediction results. More importantly, in-depth analyses of the attention values output by DeepHINT revealed intriguing mechanistic implications in the selection of HIV integration sites, including potential roles of several DNA-binding proteins. These results established DeepHINT as an effective and explainable deep learning framework for the prediction and mechanistic study of HIV integration. Availability and implementation DeepHINT is available as an open-source software and can be downloaded from https://github.com/nonnerdling/DeepHINT. Supplementary information Supplementary data are available at Bioinformatics online.
Year
DOI
Venue
2019
10.1093/bioinformatics/bty842
BIOINFORMATICS
Field
DocType
Volume
Genome,Biology,Latency (engineering),DNA sequencing,Artificial intelligence,Computational biology,Deep learning,Genetics,Zinc finger,HIV integration,Transcription factor
Journal
35
Issue
ISSN
Citations 
10
1367-4803
2
PageRank 
References 
Authors
0.38
2
9
Name
Order
Citations
PageRank
Hailin Hu143.17
An Xiao290.83
Sai Zhang321.73
Yangyang Li4201.99
Xuanling Shi530.73
Tao Jiang61809155.32
Linqi Zhang720.38
Lei Zhang820.38
Jianyang Zeng913516.82