A comparative study of COVID-19 transcriptional signatures between clinical samples and preclinical cell models in the search for disease master regulators and drug repositioning candidates

Chapola, Henrique; Bastiani, Marco Antônio De; Duarte, Marcelo Mendes; Freitas, Matheus Becker; Schuster, Jussara Severo; Vargas, Daiani Machado de; Klamt, Fábio

doi:10.1016/j.virusres.2023.199053

Cited by 3 publications

(2 citation statements)

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“…Finally, we conducted predictive analysis on the transcriptional regulation mechanisms and potential therapeutic drugs of KCNK12 and hub genes, including MYC [31] ESR1 [32] CTCF [33] SNAI2 [34] JUND [35] is closely related to acute stroke. MYC plays an important role in neuronal repair after ischemia, and JUND regulates IL-1 β Improving cerebral vascular reperfusion injury, ZBTB7A promotes cell survival after coronavirus infection[36], CREB1 identi ed as an important transcription factor in stroke mice [37], MYB is involved in cortical and striatal damage in mouse brain after I/R[38], SP1 has a bidirectional effect in ischemic stroke [39], CBX3 is associated with COVID19 infection [40], TAL1 is considered the main regulatory factor of COVID19 [41], Correlation between TET2 and in ammatory response in ischemic stroke.…”

Section: Discussionmentioning

confidence: 99%

KCNK12 as a novel immune-related biomarker to reveal the crosstalk between COVID19 and stroke

Han,

Li,

Zhang

et al. 2023

Preprint

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Background COVID-19, a respiratory disease that emerged in 2019, continues to pose a global threat to public health. Stroke has become the second leading cause of death worldwide, with respiratory infections among its serious complications. COVID-19 infection and mortality rates are notably higher among stroke patients than in the general population. However, the potential relationship between COVID-19 and stroke remains poorly understood. This article aims to elucidate the potential mechanisms underlying the association between these two diseases at the transcriptome level and to identify potentially useful drugs. Results KCNK12 was identified as an important stroke biomarker and showed significant differential expression in COVID-19 by intersecting multiple algorithms. Functional enrichment analysis revealed that KCNK12 primarily promotes neuroactive ligand-receptor interaction (p.adj < 0.001). Analysis of immune infiltration showed that neutrophils in the peripheral blood of stroke patients are the most affected by KCNK12. Moreover, there was a significant correlation between neuroactive ligand-receptor interaction and neutrophil infiltration (R = 0.65, p < 2.2e-16). The relationship between KCNK12 and neutrophil infiltration was further validated using single-cell data Conclusion We have identified KCNK12 as a potential target that may contribute to the susceptibility of stroke patients to COVID-19 infection. KCNK12 regulates neutrophil infiltration through neuroactive ligand-receptor interaction. This discovery not only sheds light on the underlying mechanisms of the relationship between stroke and COVID-19 but also provides predictions for transcription factors and potential drugs that can be used as therapeutic options.

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Section: Discussionmentioning

confidence: 99%

KCNK12 as a novel immune-related biomarker to reveal the crosstalk between COVID19 and stroke

Han,

Li,

Zhang

et al. 2023

Preprint

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show abstract

“…According to their study, the expression of KLF2 was reduced in endothelial cells of patients, and thus augmenting KLF2 levels may be therapeutically beneficial. Chapola et al [ 9 ] have identified COVID-19 Master Regulators (MRs) from lung tissues of patients who developed the severe form of the disease. Such MRs include transcription factors such as TAL1, TEAD4, EPAS1, ATOH8, ERG, and ARNTL2.…”

Section: Introductionmentioning

confidence: 99%

Transcription Factor Driven Gene Regulation in COVID-19 Patients

Santoni

Ghosh

Derelitto

et al. 2023

Viruses

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SARS-CoV-2 and its many variants have caused a worldwide emergency. Host cells colonised by SARS-CoV-2 present a significantly different gene expression landscape. As expected, this is particularly true for genes that directly interact with virus proteins. Thus, understanding the role that transcription factors can play in driving differential regulation in patients affected by COVID-19 is a focal point to unveil virus infection. In this regard, we have identified 19 transcription factors which are predicted to target human proteins interacting with Spike glycoprotein of SARS-CoV-2. Transcriptomics RNA-Seq data derived from 13 human organs are used to analyse expression correlation between identified transcription factors and related target genes in both COVID-19 patients and healthy individuals. This resulted in the identification of transcription factors showing the most relevant impact in terms of most evident differential correlation between COVID-19 patients and healthy individuals. This analysis has also identified five organs such as the blood, heart, lung, nasopharynx and respiratory tract in which a major effect of differential regulation mediated by transcription factors is observed. These organs are also known to be affected by COVID-19, thereby providing consistency to our analysis. Furthermore, 31 key human genes differentially regulated by the transcription factors in the five organs are identified and the corresponding KEGG pathways and GO enrichment are also reported. Finally, the drugs targeting those 31 genes are also put forth. This in silico study explores the effects of transcription factors on human genes interacting with Spike glycoprotein of SARS-CoV-2 and intends to provide new insights to inhibit the virus infection.

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A weighted integration method based on graph representation learning for drug repositioning

Lian,

Ding,

et al. 2024

Applied Soft Computing

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A comparative study of COVID-19 transcriptional signatures between clinical samples and preclinical cell models in the search for disease master regulators and drug repositioning candidates

Cited by 3 publications

References 85 publications

KCNK12 as a novel immune-related biomarker to reveal the crosstalk between COVID19 and stroke

KCNK12 as a novel immune-related biomarker to reveal the crosstalk between COVID19 and stroke

Transcription Factor Driven Gene Regulation in COVID-19 Patients

A weighted integration method based on graph representation learning for drug repositioning

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