Significance of interferon signaling based on mRNA-microRNA integration and plasma protein analyses in critically ill COVID-19 patients

Togami, Yuki; Matsumoto, Hisatake; Yoshimura, Jumpei; Matsubara, Tsunehiro; Ebihara, Takeshi; Mizunuma, Hiroshi; Mitsuyama, Yumi; Kojima, Takashi; Ishikawa, Masakazu; Sugihara, Fuminori; Hirata, Haruhiko; Okuzaki, Daisuke; Ogura, Hiroshi

doi:10.1016/j.omtn.2022.07.005

Cited by 14 publications

(25 citation statements)

References 23 publications

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“…The RNA sequence (RNA-Seq) analysis was performed as shown in a previous article [14]. The sequenced reads were mapped to the human reference genome sequences (hg19) using TopHat, version 2.1.1, in combination with Bowtie2, version 2.2.8, and SAMtools, version 0.1.18.…”

Section: Rna Sequence Analysismentioning

confidence: 99%

“…The analysis was performed as shown in a previous article [14]. Small RNA libraries were constructed following manufacturer instructions using NEBNext Small RNA Library Prep Set for Illumina (New England Biolabs, Ipswich, MA) and sequenced on the NovaSeq 6000 platform (Illumina) in 101-bp singleend reads.…”

Section: Mirna Sequencing and Mirna-seq Analysismentioning

confidence: 99%

“…The analysis was performed with some modi cations as shown in a previous article [14]. We normalized mRNA raw count data using Integrated Differential Expression and Pathway analysis, version 0.96 (iDEP.96).…”

Section: Statistical Analysis Of Mrna and Mirnamentioning

confidence: 99%

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Integrated analysis of messenger RNA and microRNA in patients with community- acquired pneumonia-associated sepsis

Oda

Matsumoto

Togami

et al. 2023

Preprint

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Background: Community-acquired pneumonia (CAP) is defined as an acute lung infection involving the alveoli that occurs in a patient without recent health care exposure. A complication of CAP is severe sepsis, a syndrome of infection often accompanied by systemic inflammation and organ dysfunction. The aim of this study was to evaluate mRNA and miRNA in whole blood and to perform an integrative analysis to assess cellular signals that play a role in the pathogenesis of patients with CAP-associated sepsis. Methods: This was a prospective, observational, single-center study of patients transported to the Department of Traumatology and Acute Critical Medicine, Graduate School of Medicine, Osaka University. Patients with CAP-associated sepsis were analyzed. The diagnosis of pneumonia was made according to the clinical findings, including blood samples and chest computed tomography scan, and the diagnosis of sepsis followed the Sepsis-3 guidelines. Results: We included 14 critically ill patients with CAP-associated sepsis and 15 healthy control subjects (HCS). The median ages of the patient group and HCS were 78 and 55 years, and their body mass indexes were 22.8 and 21.7 kg/m2, respectively. All patients were treated at the critical care center, and 11 of the 14 patients received ventilatory management. All patients survived. These 14 patients met the diagnostic criteria of Sepsis-3 and were diagnosed as having CAP-associated sepsis. Of them, 6 patients met the diagnostic criteria for septic shock. RNA sequencing showed the number of genes with up:down (upregulated:downregulated) expression variation (false discovery rate [FDR] <0.05, |log2 fold change| >1.2) to be 1209:1461 for mRNA; 51:21 for microRNA; and 646:1274 for miRNA-targeted mRNA. Canonical pathway analysis using mRNA showed activation of the PD-1 and PD-L1 cancer immunotherapy signaling pathways and inhibition of the Th1 signaling pathway as well as that using miRNA-targeted mRNAs. Conclusions: Using integrated analysis of mRNA and miRNA, we elucidated for the first time, to our knowledge, that T-cell exhaustion occurred during the acute phase of CAP-associated sepsis and that miRNA regulated Th1 signaling and PD-1 and PD-L1 cancer immunotherapy signaling through the RNA interference action of mRNA.

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Section: Rna Sequence Analysismentioning

confidence: 99%

Section: Mirna Sequencing and Mirna-seq Analysismentioning

confidence: 99%

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Integrated analysis of messenger RNA and microRNA in patients with community- acquired pneumonia-associated sepsis

Oda

Matsumoto

Togami

et al. 2023

Preprint

Self Cite

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show abstract

“…The analysis was performed with some modi cations as shown in a previous article (7). The sequenced reads were aligned to the human reference genome sequences (hg19) using TopHat (version 2.1.1) in conjunction with Bowtie2 (version 2.2.8) and SAMtools (version 0.1.18).…”

Section: Rna-seq Analysismentioning

confidence: 99%

“…Raw read counts of gene-level expression were determined with featureCounts using the subread-2.0.0 package. miRNA Sequencing and miRNA-Seq Analysis This analysis was performed with some modi cations as shown in a previous article (7). Small RNA libraries were prepared using the NEBNext Small RNA Library Prep Set for Illumina (New England Biolabs, Ipswich, MA) according to the manufacturer's instructions.…”

Section: Rna-seq Analysismentioning

confidence: 99%

Comparative Analysis of Host Responses Between Sepsis and COVID-19: A Prospective Observational Study of Whole Blood Transcriptome

Muratsu,

Onishi,

Yoshimura

et al. 2023

Preprint

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OBJECTIVES: This study aimed to comprehensively compare host responses to sepsis and COVID-19 by analyzing messenger RNA (mRNA) and microRNA (miRNA) profiles to shed light on their distinct pathophysiological mechanisms. DESIGN: Prospective observational study SETTING: Whole blood RNA sequencing was used to analyze mRNA and miRNA profiles of patients diagnosed as having sepsis or COVID-19 at the Department of Trauma and Emergency Medicine, Osaka University Graduate School of Medicine. PATIENTS: Twenty-two sepsis patients, 35 COVID-19 patients, and 15 healthy subjects admitted to the department were included. We diagnosed sepsis patients according to the Sepsis-3 criterion that the Sequential Organ Failure Assessment score must increase to 2 points or more among patients with suspected infections. COVID-19 patients were diagnosed using SARS-CoV-2 RT-PCR testing, and presence of pneumonia was assessed through chest computed tomography scans. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For RNA sequencing, 14,500 mRNAs, 1121 miRNAs, and 2556 miRNA-targeted mRNAs were available for analysis in sepsis patients. Numbers of genes showing upregulated:downregulated gene expression (false discovery rate <0.05, |log2 fold change| >1.5) were 256:2887 for mRNA, 53:5 for miRNA, and 49:2507 for miRNA-targeted mRNA. Similarly, in COVID-19 patients, 14,500 mRNAs, 1121 miRNAs, and 327 miRNA-targeted mRNAs were analyzed, with numbers of genes exhibiting upregulated:downregulated gene expression of 672:1147 for mRNA, 3:4 for miRNA, and 165:162 for miRNA-targeted mRNA. This analysis revealed significant differences in the numbers of upregulated and downregulated genes expressed and pathways between the sepsis and COVID-19 patients. Sepsis patients showed activation of the PD-1 and PD-L1 cancer immunotherapy signaling pathway and concurrent suppression of Th1 signaling. CONCLUSION: Our study illuminated distinct molecular variances between sepsis and COVID-19. Sepsis patients had a greater number of upregulated and downregulated genes and pathways compared to COVID-19 patients, indicating a dynamic change in gene expression and pathway activation in sepsis.

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Importance of microRNAs by mRNA-microRNA integration analysis in acute ischemic stroke patients

Kanki

Matsumoto

Togami

et al. 2023

Journal of Stroke and Cerebrovascular Diseases

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Significance of interferon signaling based on mRNA-microRNA integration and plasma protein analyses in critically ill COVID-19 patients

Cited by 14 publications

References 23 publications

Integrated analysis of messenger RNA and microRNA in patients with community- acquired pneumonia-associated sepsis

Integrated analysis of messenger RNA and microRNA in patients with community- acquired pneumonia-associated sepsis

Comparative Analysis of Host Responses Between Sepsis and COVID-19: A Prospective Observational Study of Whole Blood Transcriptome

Importance of microRNAs by mRNA-microRNA integration analysis in acute ischemic stroke patients

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