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

Jiaxing Chen1, ChinWang Cheong1, Liang Lan1

  • 1Department of Computer Science, Hong Kong Baptist University, Waterloo Road, Kowloon Tong, Hong Kong.

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|August 23, 2021
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Summary

DeepDRIM, a novel deep neural network, reconstructs gene regulatory networks (GRNs) from single-cell RNA sequencing data. It effectively identifies cell-type-specific GRN alterations in diseases like COVID-19.

Keywords:
deep neural networkgene regulatory networksingle-cell RNA sequencingtransitive interactions

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Area of Science:

  • Genomics
  • Computational Biology
  • Bioinformatics

Background:

  • Single-cell RNA sequencing (scRNA-seq) allows high-resolution gene activity analysis.
  • Reconstructing cell-type-specific gene regulatory networks (GRNs) from scRNA-seq data is challenging due to dropout events and cellular heterogeneity.
  • Existing GRN reconstruction algorithms are often designed for bulk RNA-seq and struggle with scRNA-seq data characteristics.

Purpose of the Study:

  • To develop a novel supervised deep neural network, DeepDRIM, for accurate GRN reconstruction from scRNA-seq data.
  • To address the limitations of existing methods in handling scRNA-seq data, including dropout events and cellular heterogeneity.
  • To apply DeepDRIM for analyzing cell-type-specific GRN alterations in diseases, specifically COVID-19.

Main Methods:

  • Representing joint gene expression distribution of gene pairs as images.
  • Utilizing a supervised deep neural network (DeepDRIM) that processes TF-gene pair images and neighborhood context.
  • Comparing DeepDRIM against nine existing GRN reconstruction algorithms on scRNA-seq data from eight cell lines.

Main Results:

  • DeepDRIM demonstrated superior performance in GRN reconstruction from scRNA-seq data compared to existing algorithms.
  • The method proved robust to dropout rates, cell numbers, and training data size in simulations.
  • Application to COVID-19 patient B cells revealed cell-type-specific GRN alterations enriched in pathways like lysosome, apoptosis, and response to hypoxia.

Conclusions:

  • DeepDRIM offers an effective approach for reconstructing GRNs from scRNA-seq data, outperforming existing methods.
  • The tool is robust and reliable across various data conditions, including dropout events and varying sample sizes.
  • DeepDRIM facilitates the discovery of disease-associated GRN alterations, providing insights into disease mechanisms, as demonstrated in COVID-19.