Evidence map›Paper›PMID 33341869›Full record

ArticleBriefings in bioinformatics2021

Inferring microenvironmental regulation of gene expression from single-cell RNA sequencing data using scMLnet with an application to COVID-19.

Jinyu Cheng, Ji Zhang, Zhongdao Wu, Xiaoqiang Sun

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Briefings in bioinformatics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 79 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 1 pooled it
6.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

79 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.

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  12. Revisiting the critical roles of reactive microglia in traumatic brain injury.International journal of surgery (London, England) · 2025
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19 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Jinyu ChengZhong-Shan School of Medicine, Sun Yat-Sen University.
Ji ZhangDepartment of Neurosurgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center.
Zhongdao WuZhong-Shan School of Medicine, Sun Yat-Sen University.
Xiaoqiang SunZhong-Shan School of Medicine, Sun Yat-Sen University.
Sun Yat-sen University · CNSun Yat-sen University Cancer Center · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Inferring how gene expression in a cell is influenced by cellular microenvironment is of great importance yet challenging. In this study, we present a single-cell RNA-sequencing data based multilayer network method (scMLnet) that models not only functional intercellular communications but also intracellular gene regulatory networks (https://github.com/SunXQlab/scMLnet). scMLnet was applied to a scRNA-seq dataset of COVID-19 patients to decipher the microenvironmental regulation of expression of SARS-CoV-2 receptor ACE2 that has been reported to be correlated with inflammatory cytokines and COVID-19 severity. The predicted elevation of ACE2 by extracellular cytokines EGF, IFN-γ or TNF-α were experimentally validated in human lung cells and the related signaling pathway were verified to be significantly activated during SARS-COV-2 infection. Our study provided a new approach to uncover inter-/intra-cellular signaling mechanisms of gene expression and revealed microenvironmental regulators of ACE2 expression, which may facilitate designing anti-cytokine therapies or targeted therapies for controlling COVID-19 infection. In addition, we summarized and compared different methods of scRNA-seq based inter-/intra-cellular signaling network inference for facilitating new methodology development and applications.

Indexed as

Gene Expression RegulationAngiotensin-Converting Enzyme 2COVID-19CytokinesDatasets as TopicHumansSequence Analysis, RNASingle-Cell AnalysisACE2 protein, humanAngiotensin-Converting Enzyme 2Cytokinescellular microenvironmentmultilayer networkSARS-CoV-2scMLnetsingle-cell RNA-seq

Identifiers

PMID33341869
PMCPMC7799217
OpenAlexW3114457750

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.