DeepDRIM – a deep neural network to reconstruct cell-type-specific gene regulatory network using single-cell RNA-seq data

Single-cell RNA sequencing has enabled to capture the gene activities at single-cell resolution, thus allowing reconstruction of cell-type-specific gene regulatory networks (GRNs). The available algorithms for reconstructing GRNs are commonly designed for bulk RNA-seq data, and few of them are applicable to analyze scRNA-seq data by dealing with the dropout events and cellular heterogeneity. Researchers from Hong Kong Baptist University represent the joint gene expression distribution of a gene pair as an image and propose a novel supervised deep neural network called DeepDRIM which utilizes the image of the target TF-gene pair and the ones of the potential neighbors to reconstruct GRN from scRNA-seq data. Due to the consideration of TF-gene pair’s neighborhood context, DeepDRIM can effectively eliminate the false positives caused by transitive gene–gene interactions. The researchers compared DeepDRIM with nine GRN reconstruction algorithms designed for either bulk or single-cell RNA-seq data. It achieves evidently better performance for the scRNA-seq data collected from eight cell lines. The simulated data show that DeepDRIM is robust to the dropout rate, the cell number and the size of the training data. They further applied DeepDRIM to the scRNA-seq gene expression of B cells from the bronchoalveolar lavage fluid of the patients with mild and severe coronavirus disease 2019. The researchers focused on the cell-type-specific GRN alteration and observed targets of TFs that were differentially expressed between the two statuses to be enriched in lysosome, apoptosis, response to decreased oxygen level and microtubule, which had been proved to be associated with coronavirus infection.

Overview of DeepDRIM

rna-seq

A. Representation of the joint gene expression of gene a and gene b as a primary image. B. The 2n + 2 neighbor images are generated from the genes with strong positive covariance with gene a or gene b. C. The network architecture of DeepDRIM, including Network A and Network B, which are two stacked convolutional embedding structures designed to process the primary and neighbor images, respectively. D. An example for the prediction of a cell-type-specific GRN using DeepDRIM.

Availability – DeepDRIM is available at https://github.com/jiaxchen2-c/DeepDRIM.

Chen J, Cheong C, Lan L, Zhou X, Liu J, Lyu A, Cheung WK, Zhang L. (2021)  DeepDRIM: a deep neural network to reconstruct cell-type-specific gene regulatory network using single-cell RNA-seq data. Brief Bioinform [Epub ahead of print]. [abstract]

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