ScRNA-seq expression of<i>IFI27</i>and<i>APOC2</i>identifies four alveolar macrophage superclusters in healthy BALF

Li, Xin; Kolling, Fred; Aridgides, Daniel; Mellinger, Diane; Ashare, Alix; Jakubzick, Claudia

doi:10.26508/lsa.202201458

Cited by 25 publications

(24 citation statements)

References 80 publications

(119 reference statements)

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“…IFI27 is also upregulated in the peripheral blood of COVID-19 patients ( 10 , 11 , 13 ) and may serve as a biomarker for pre-symptomatic SARS-CoV-2 infection ( 14 ). These data are consistent with observations that the induction of type I interferons in the lower respiratory tract and systemically is associated with immunopathology ( 15 ) whilst the induction of type I interferons in the upper respiratory tract is associated with virus control and not disease outcomes ( 12 ). However, others have suggested that IFI27 expression is low in patients with severe COVID ( 16 , 17 ).…”

Section: Introductionsupporting

confidence: 91%

“…Preliminary evidence suggests that IFI27 expression may be a useful biomarker for COVID-19 diagnosis ( 8 – 11 ). In the respiratory tract, IFI27 expression is significantly upregulated by SARS-CoV-2 infection, more so than by other respiratory viruses ( 8 , 9 , 12 ). IFI27 is also upregulated in the peripheral blood of COVID-19 patients ( 10 , 11 , 13 ) and may serve as a biomarker for pre-symptomatic SARS-CoV-2 infection ( 14 ).…”

Section: Introductionmentioning

confidence: 97%

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IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study

et al. 2023

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PurposeRobust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness.MethodsWe conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 (IFI27) in COVID-19 patients.ResultsWe show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 influenza virus infection, IFI27-like genes were highly upregulated in the blood samples of severely infected patients.ConclusionThese data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus.

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Section: Introductionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 97%

IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study

et al. 2023

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“…Inhibiting the classical NF-κB signaling pathway blocks growth hormone (GH) or insulin-like growth factor (IGF-1) signaling, suppresses cell proliferation, and suppresses bone morphogenetic protein 2 (BMP2) expression, thereby promoting apoptosis (Jimi et al, 2019). Most importantly, these three genes were all involved a lot in the inflammatory response (Zhang Z. et al, 2021;Zhu et al, 2021;Li et al, 2022), stating that inflammatory response was a main regulated pathway in IPF and these three genes could modulate the pathological process of IPF through this pathway.…”

Section: Discussionmentioning

confidence: 99%

A novel gene signature based on the hub genes of COVID-19 predicts the prognosis of idiopathic pulmonary fibrosis

et al. 2022

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Background: Increasing evidence has demonstrated that there was a strong correlation between COVID-19 and idiopathic pulmonary fibrosis (IPF). However, the studies are limited, and the real biological mechanisms behind the IPF progression were still uncleared.Methods: GSE70866 and GSE 157103 datasets were downloaded. The weight gene co-expression network analysis (WGCNA) algorithms were conducted to identify the most correlated gene module with COVID-19. Then the genes were extracted to construct a risk signature in IPF patients by performing Univariate and Lasso Cox Regression analysis. Univariate and Multivariate Cox Regression analyses were used to identify the independent value for predicting the prognosis of IPF patients. What’s more, the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and gene set enrichment analysis (GSEA) were conducted to unveil the potential biological pathways. CIBERSORT algorithms were performed to calculate the correlation between the risk score and immune cells infiltrating levels.Results: Two hundred thirty three differentially expressed genes were calculated as the hub genes in COVID-19. Fourteen of these genes were identified as the prognostic differentially expressed genes in IPF. Three (MET, UCHL1, and IGF1) of the fourteen genes were chosen to construct the risk signature. The risk signature can greatly predict the prognosis of high-risk and low-risk groups based on the calculated risk score. The functional pathway enrichment analysis and immune infiltrating analysis showed that the risk signature may regulate the immune-related pathways and immune cells.Conclusion: We identified prognostic differentially expressed hub genes related to COVID-19 in IPF. A risk signature was constructed based on those genes and showed great value for predicting the prognosis in IPF patients. What’s more, three genes in the risk signature may be clinically valuable as potential targets for treating IPF patients and IPF patients with COVID-19.

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“…Dataset (GSE193782) was derived from the Gene Expression Omnibus database (GEO) ( https://www.ncbi.nlm.nih.gov/geo/ ). Single-cell sequencing data from four healthy controls and three CF patients were included in the GSE193782 dataset ( 18 ). Bronchoalveolar lavage fluid (BALF) was used as the sample in the study.…”

Section: Methodsmentioning

confidence: 99%

Lack of association between leptin concentrations and cystic fibrosis: A meta-analysis and regression

et al. 2023

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BackgroundLeptin (LEP) acts as a proinflammatory cytokine and may play an important role in the pathophysiology of cystic fibrosis (CF). This review aimed to assess the quantitative difference in leptin status between CF patients and non-CF controls.MethodsIn this study, the researchers conducted systematic searches of various databases, such as PubMed, Excerpta Medica Database, Google Scholar, Web of Science, and the China National Knowledge Infrastructure. The data collected from the above databases were assessed using the Stata 11.0 and R 4.1.3 software. The correlation coefficients and the Standardized Mean Differences (SMD) were employed to assess the effect size. A combination analysis was also carried out with the help of either a fixed-effects or random-effects model. In addition, the single-cell sequencing GSE193782 dataset was obtained to determine the mRNA expression levels of LEP and leptin receptor (LEPR) in the bronchoalveolar lavage fluid, to verify the different leptin expression between the CF patients and healthy controls.ResultsA total of 919 CF patients and 397 controls from 14 articles were included in this study. CF patients and non-CF controls showed similar serum/plasma leptin levels. Gender, specimen testing, age, and study design were all taken into account for carrying out subgroup analyses. The results revealed no variations in serum/plasma leptin levels between the controls and CF patients in the various subgroups. Female CF patients exhibited higher leptin concentrations compared to male CF patients, and male healthy individuals showed lower leptin levels than female healthy participants. Aside from the fact that serum/plasma leptin appeared to be favorably linked to fat mass and BMI, the findings in this study also indicated that serum/plasma concentrations were not associated with Forced Expiratory Volume in the first second (FEV1). No statistically significant differences were observed in the leptin and leptin receptor mRNA expression levels between the healthy controls and CF patients. The leptin receptor and leptin expression levels in alveolar lavage fluid were low in various cells, without any distinctive distribution patterns.ConclusionsThe current meta-analysis indicated the absence of significant differences in leptin levels between CF patients and healthy individuals. Gender, fat mass, and BMI may all be correlated with leptin concentrations.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022380118.

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ScRNA-seq expression ofIFI27andAPOC2identifies four alveolar macrophage superclusters in healthy BALF

Cited by 25 publications

References 80 publications

IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study

IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study

A novel gene signature based on the hub genes of COVID-19 predicts the prognosis of idiopathic pulmonary fibrosis

Lack of association between leptin concentrations and cystic fibrosis: A meta-analysis and regression

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