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Predicting gene regulatory networks from cell atlases.

ABSTRACT: Recent single-cell RNA-sequencing atlases have surveyed and identified major cell types across different mouse tissues. Here, we computationally reconstruct gene regulatory networks from three major mouse cell atlases to capture functional regulators critical for cell identity, while accounting for a variety of technical differences, including sampled tissues, sequencing depth, and author assigned cell type labels. Extracting the regulatory crosstalk from mouse atlases, we identify and distinguish global regulons active in multiple cell types from specialised cell type-specific regulons. We demonstrate that regulon activities accurately distinguish individual cell types, despite differences between individual atlases. We generate an integrated network that further uncovers regulon modules with coordinated activities critical for cell types, and validate modules using available experimental data. Inferring regulatory networks during myeloid differentiation from wild-type and Irf8 KO cells, we uncover functional contribution of Irf8 regulon activity and composition towards monocyte lineage. Our analysis provides an avenue to further extract and integrate the regulatory crosstalk from single-cell expression data.

SUBMITTER: Moller AF

PROVIDER: S-EPMC7536823 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Predicting gene regulatory networks from cell atlases.

Møller Andreas Fønss AF Natarajan Kedar Nath KN

Life science alliance 20200921 11

Recent single-cell RNA-sequencing atlases have surveyed and identified major cell types across different mouse tissues. Here, we computationally reconstruct gene regulatory networks from three major mouse cell atlases to capture functional regulators critical for cell identity, while accounting for a variety of technical differences, including sampled tissues, sequencing depth, and author assigned cell type labels. Extracting the regulatory crosstalk from mouse atlases, we identify and distingui ...[more]

PMID: 32958603

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Project description:Single-cell RNA-sequencing (scRNA-seq) has emerged as a powerful technique for studying gene expression patterns at the single-cell level. Inferring gene regulatory networks (GRNs) from scRNA-seq data provides insight into cellular phenotypes from the genomic level. However, the high sparsity, noise and dropout events inherent in scRNA-seq data present challenges for GRN inference. In recent years, the dramatic increase in data on experimentally validated transcription factors binding to DNA has made it possible to infer GRNs by supervised methods. In this study, we address the problem of GRN inference by framing it as a graph link prediction task. In this paper, we propose a novel framework called GNNLink, which leverages known GRNs to deduce the potential regulatory interdependencies between genes. First, we preprocess the raw scRNA-seq data. Then, we introduce a graph convolutional network-based interaction graph encoder to effectively refine gene features by capturing interdependencies between nodes in the network. Finally, the inference of GRN is obtained by performing matrix completion operation on node features. The features obtained from model training can be applied to downstream tasks such as measuring similarity and inferring causality between gene pairs. To evaluate the performance of GNNLink, we compare it with six existing GRN reconstruction methods using seven scRNA-seq datasets. These datasets encompass diverse ground truth networks, including functional interaction networks, Loss of Function/Gain of Function data, non-specific ChIP-seq data and cell-type-specific ChIP-seq data. Our experimental results demonstrate that GNNLink achieves comparable or superior performance across these datasets, showcasing its robustness and accuracy. Furthermore, we observe consistent performance across datasets of varying scales. For reproducibility, we provide the data and source code of GNNLink on our GitHub repository: https://github.com/sdesignates/GNNLink.

Dataset Information

Predicting gene regulatory networks from cell atlases.

Publications

Predicting gene regulatory networks from cell atlases.

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