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Inferring Gene Regulatory Networks From Single-Cell Transcriptomic Data Using Bidirectional RNN

Accurate inference of gene regulatory rules is critical to understanding cellular processes. Existing computational methods usually decompose the inference of gene regulatory networks (GRNs) into multiple subproblems, rather than detecting potential causal relationships simultaneously, which limits...

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Autores principales: Gan, Yanglan, Hu, Xin, Zou, Guobing, Yan, Cairong, Xu, Guangwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178250/
https://www.ncbi.nlm.nih.gov/pubmed/35692809
http://dx.doi.org/10.3389/fonc.2022.899825
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author Gan, Yanglan
Hu, Xin
Zou, Guobing
Yan, Cairong
Xu, Guangwei
author_facet Gan, Yanglan
Hu, Xin
Zou, Guobing
Yan, Cairong
Xu, Guangwei
author_sort Gan, Yanglan
collection PubMed
description Accurate inference of gene regulatory rules is critical to understanding cellular processes. Existing computational methods usually decompose the inference of gene regulatory networks (GRNs) into multiple subproblems, rather than detecting potential causal relationships simultaneously, which limits the application to data with a small number of genes. Here, we propose BiRGRN, a novel computational algorithm for inferring GRNs from time-series single-cell RNA-seq (scRNA-seq) data. BiRGRN utilizes a bidirectional recurrent neural network to infer GRNs. The recurrent neural network is a complex deep neural network that can capture complex, non-linear, and dynamic relationships among variables. It maps neurons to genes, and maps the connections between neural network layers to the regulatory relationship between genes, providing an intuitive solution to model GRNs with biological closeness and mathematical flexibility. Based on the deep network, we transform the inference of GRNs into a regression problem, using the gene expression data at previous time points to predict the gene expression data at the later time point. Furthermore, we adopt two strategies to improve the accuracy and stability of the algorithm. Specifically, we utilize a bidirectional structure to integrate the forward and reverse inference results and exploit an incomplete set of prior knowledge to filter out some candidate inferences of low confidence. BiRGRN is applied to four simulated datasets and three real scRNA-seq datasets to verify the proposed method. We perform comprehensive comparisons between our proposed method with other state-of-the-art techniques. These experimental results indicate that BiRGRN is capable of inferring GRN simultaneously from time-series scRNA-seq data. Our method BiRGRN is implemented in Python using the TensorFlow machine-learning library, and it is freely available at https://gitee.com/DHUDBLab/bi-rgrn.
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spelling pubmed-91782502022-06-10 Inferring Gene Regulatory Networks From Single-Cell Transcriptomic Data Using Bidirectional RNN Gan, Yanglan Hu, Xin Zou, Guobing Yan, Cairong Xu, Guangwei Front Oncol Oncology Accurate inference of gene regulatory rules is critical to understanding cellular processes. Existing computational methods usually decompose the inference of gene regulatory networks (GRNs) into multiple subproblems, rather than detecting potential causal relationships simultaneously, which limits the application to data with a small number of genes. Here, we propose BiRGRN, a novel computational algorithm for inferring GRNs from time-series single-cell RNA-seq (scRNA-seq) data. BiRGRN utilizes a bidirectional recurrent neural network to infer GRNs. The recurrent neural network is a complex deep neural network that can capture complex, non-linear, and dynamic relationships among variables. It maps neurons to genes, and maps the connections between neural network layers to the regulatory relationship between genes, providing an intuitive solution to model GRNs with biological closeness and mathematical flexibility. Based on the deep network, we transform the inference of GRNs into a regression problem, using the gene expression data at previous time points to predict the gene expression data at the later time point. Furthermore, we adopt two strategies to improve the accuracy and stability of the algorithm. Specifically, we utilize a bidirectional structure to integrate the forward and reverse inference results and exploit an incomplete set of prior knowledge to filter out some candidate inferences of low confidence. BiRGRN is applied to four simulated datasets and three real scRNA-seq datasets to verify the proposed method. We perform comprehensive comparisons between our proposed method with other state-of-the-art techniques. These experimental results indicate that BiRGRN is capable of inferring GRN simultaneously from time-series scRNA-seq data. Our method BiRGRN is implemented in Python using the TensorFlow machine-learning library, and it is freely available at https://gitee.com/DHUDBLab/bi-rgrn. Frontiers Media S.A. 2022-05-26 /pmc/articles/PMC9178250/ /pubmed/35692809 http://dx.doi.org/10.3389/fonc.2022.899825 Text en Copyright © 2022 Gan, Hu, Zou, Yan and Xu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Gan, Yanglan
Hu, Xin
Zou, Guobing
Yan, Cairong
Xu, Guangwei
Inferring Gene Regulatory Networks From Single-Cell Transcriptomic Data Using Bidirectional RNN
title Inferring Gene Regulatory Networks From Single-Cell Transcriptomic Data Using Bidirectional RNN
title_full Inferring Gene Regulatory Networks From Single-Cell Transcriptomic Data Using Bidirectional RNN
title_fullStr Inferring Gene Regulatory Networks From Single-Cell Transcriptomic Data Using Bidirectional RNN
title_full_unstemmed Inferring Gene Regulatory Networks From Single-Cell Transcriptomic Data Using Bidirectional RNN
title_short Inferring Gene Regulatory Networks From Single-Cell Transcriptomic Data Using Bidirectional RNN
title_sort inferring gene regulatory networks from single-cell transcriptomic data using bidirectional rnn
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178250/
https://www.ncbi.nlm.nih.gov/pubmed/35692809
http://dx.doi.org/10.3389/fonc.2022.899825
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