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Different from the bulk expression data, single-cell transcriptomic data embody cell-to-cell variance and diverse biological information, such as tissue characteristics, transformation of cell types, etc. Inferring GRNs based on such data offers unprecedented advantages for making a profound study of cell phenotypes, revealing gene functions and exploring potential interactions. However, the high sparsity, noise and dropout events of single-cell transcriptomic data pose new challenges for regulation identification. We develop a hybrid deep learning framework for GRN inference from single-cell transcriptomic data, DGRNS, which encodes the raw data and fuses recurrent neural network and convolutional neural network (CNN) to train a model capable of distinguishing related gene pairs from unrelated gene pairs. To overcome the limitations of such datasets, it applies sliding windows to extract valuable features while preserving the direction of regulation. DGRNS is constructed as a deep learning model containing gated recurrent unit network for exploring time-dependent information and CNN for learning spatially related information. Our comprehensive and detailed comparative analysis on the dataset of mouse hematopoietic stem cells illustrates that DGRNS outperforms state-of-the-art methods. The networks inferred by DGRNS are about 16% higher than the area under the receiver operating characteristic curve of other unsupervised methods and 10% higher than the area under the precision recall curve of other supervised methods. Experiments on human datasets show the strong robustness and excellent generalization of DGRNS. By comparing the predictions with standard network, we discover a series of novel interactions which are proved to be true in some specific cell types. Importantly, DGRNS identifies a series of regulatory relationships with high confidence and functional consistency, which have not yet been experimentally confirmed and merit further research.<\/jats:p>","DOI":"10.1093\/bib\/bbab568","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T12:07:56Z","timestamp":1639397276000},"source":"Crossref","is-referenced-by-count":79,"title":["A hybrid deep learning framework for gene regulatory network inference from single-cell transcriptomic data"],"prefix":"10.1093","volume":"23","author":[{"given":"Mengyuan","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Computer Science and Technology, College of Intelligence and Computing, Tianjin University, Tianjin, China"}]},{"given":"Wenying","family":"He","sequence":"additional","affiliation":[{"name":"School of Artificial Intelligence, Hebei University of Technology, Tianjin, China"}]},{"given":"Jijun","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology, College of Intelligence and Computing, Tianjin University, Tianjin, China"},{"name":"School of Computational Science and Engineering, University of South Carolina, Columbia, U.S"}]},{"given":"Quan","family":"Zou","sequence":"additional","affiliation":[{"name":"Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8346-0798","authenticated-orcid":false,"given":"Fei","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Computer Science and Engineering, Central South University, Changsha 410083, China"}]}],"member":"286","published-online":{"date-parts":[[2022,1,22]]},"reference":[{"issue":"4","key":"2022031506270356200_ref1","first-page":"712","article-title":"Dynamic and modular gene regulatory networks drive the development 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