Characterisation of the blood RNA host response underpinning severity in COVID-19 patients

Infection with SARS-CoV-2 has highly variable clinical manifestations, ranging from asymptomatic infection through to life-threatening disease. Host whole blood transcriptomics can offer unique insights into the biological processes underpinning infection and disease, as well as severity. We performed whole blood RNA Sequencing of individuals with varying degrees of COVID-19 severity. We used differential expression analysis and pathway enrichment analysis to explore how the blood transcriptome differs between individuals with mild, moderate, and severe COVID-19, performing pairwise comparisons between groups. Increasing COVID-19 severity was characterised by an abundance of inflammatory immune response genes and pathways, including many related to neutrophils and macrophages, in addition to an upregulation of immunoglobulin genes. Our insights into COVID-19 severity reveal the role of immune dysregulation in the progression to severe disease and highlight the need for further research exploring the interplay between SARS-CoV-2 and the inflammatory immune response.

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Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis

Scientific Reports ◽

10.1038/s41598-021-87668-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eunyoung Emily Lee ◽

Kyoung-Ho Song ◽

Woochang Hwang ◽

Sin Young Ham ◽

Hyeonju Jeong ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Clustering Analysis ◽

Validation Cohort ◽

Inflammatory Responses ◽

Clinical Course ◽

Severe Disease ◽

Outcome Data ◽

Inflammatory Immune Response ◽

Cluster 2

AbstractThe objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.

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Deregulation of Trace Amine-Associated Receptors (TAAR) Expression and Signaling Mode in Melanoma

Biomolecules ◽

10.3390/biom12010114 ◽

2022 ◽

Vol 12 (1) ◽

pp. 114

Author(s):

Anastasia N. Vaganova ◽

Savelii R. Kuvarzin ◽

Anastasia M. Sycheva ◽

Raul R. Gainetdinov

Keyword(s):

Malignant Tumors ◽

Differential Expression Analysis ◽

Enrichment Analysis ◽

Clinicopathological Characteristics ◽

Pathway Enrichment Analysis ◽

Pathway Enrichment ◽

Low Concentrations ◽

Trace Amine ◽

Specific Association ◽

Amine Compounds

Trace amine-associated receptors (TAARs) interact with amine compounds called “trace amines” which are present in tissues at low concentrations. Recently, TAARs expression in neoplastic tumors was reported. In this study, TAARs expression was analyzed in public RNAseq datasets in nevi and melanoma samples and compared to the expression of dopamine receptors (DRDs) that are known to be involved in melanoma pathogenesis. It was found that all DRDs and TAARs are expressed in nevi at comparable levels. Differential expression analysis demonstrated the drastic decrease of TAAR1, TAAR2, TAAR5, TAAR6, and TAAR8 expression in melanomas compared to benign nevi with only TAAR6, TAAR8, and TAAR9 remaining detectable in malignant tumors. No association of TAARs expression levels and melanoma clinicopathological characteristics was observed. TAARs co-expressed genes in melanoma and nevi were selected by correlation values for comparative pathway enrichment analysis between malignant and benign neoplasia. It was found that coexpression of TAARs with genes inquired in neurotransmitter signaling is lost in melanoma, and tumor-specific association of TAAR6 expression with the mTOR pathway and inflammatory signaling is observed. It is not excluded that TAARs may have certain functions in melanoma pathogenesis, the significance of which to tumor progression is yet to be understood.

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MicroRNA-550a is associated with muscle system conferring poorer survival for esophageal cancer

Bioscience Reports ◽

10.1042/bsr20181173 ◽

2019 ◽

Vol 39 (5) ◽

Cited By ~ 2

Author(s):

Housong Hong ◽

Taisheng Liu ◽

Huazhen Wu ◽

Jinye Zhang ◽

Xiaoshun Shi ◽

...

Keyword(s):

Esophageal Cancer ◽

Survival Time ◽

Therapeutic Target ◽

Differential Expression Analysis ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Muscle System ◽

Expression Levels ◽

Potential Biomarker

Abstract Background Esophageal cancer (ESCA) is one of the most common cancers in the digestive tract. Approximately 300000 people on an average die of ESCA per year worldwide. The determination of key microRNAs for the prognosis of ESCA is of indispensable significance in the clinical treatment. Methods The differentially expressed microRNAs were screened by analyzing The Cancer Genome Atlas (TCGA) database. By using the survival data of the database, we analyzed correlation between patients’ survival time and miR-550a expression levels. Differential expression analysis and gene set enrichment analysis were performed using the targeted data. Results It was found that patients with high miR-550a expression levels had shorter survival time. Data mining and signal pathway enrichment analysis of TCGA database showed that abnormal miR-550a expressions affected the recurrence of tumors by the muscle system regulation. Conclusions Through the proposed investigation, miR-550a is found to be a potential biomarker as well as non-coding therapeutic target for esophagus cancer. These results suggest that miR-550a may serve as a therapeutic target and predictor for ESCA survival.

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Effects of a Sudden Drop in Salinity on Immune Response Mechanisms of Anadara kagoshimensis

International Journal of Molecular Sciences ◽

10.3390/ijms20184365 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4365 ◽

Cited By ~ 2

Author(s):

Mo Zhang ◽

Li Li ◽

Ying Liu ◽

Xiaolong Gao

Keyword(s):

Immune Response ◽

Signaling Pathway ◽

Transcriptome Sequencing ◽

Differential Expression Analysis ◽

Enrichment Analysis ◽

Total Count ◽

Sudden Drop ◽

Blood Lymphocytes ◽

Anadara Kagoshimensis ◽

Comparison Groups

In this experiment, the effects of a sudden drop of salinity on the immune response mechanisms of the ark shell Anadara kagoshimensis were examined by simulating the sudden drop of salinity that occurs in seawater after a rainstorm. Additionally, the differentially expressed genes (DEGs) were identified using transcriptome sequencing. When the salinity dropped from 30‰ (S30) to 14‰ (S14), the phagocytic activity of blood lymphocytes, the O2− levels produced from respiratory burst, the content of reactive oxygen species, and the activities of lysozymes and acid phosphatases increased significantly, whereas the total count of blood lymphocytes did not increase. Total count of blood lymphocytes in 22‰ salinity (S22) was significantly higher than that in any other group. The raw data obtained from sequencing were processed with Trimmomatic (Version 0.36). The expression levels of unigenes were calculated using transcripts per million (TPM) based on the effects of sequencing depth, gene length, and sample on reads. Differential expression analysis was performed using DESeq (Version 1.12.4). Transcriptome sequencing revealed 269 (101 up-regulated, 168 down-regulated), 326 (246 up-regulated, 80 down-regulated), and 185 (132 up-regulated, 53 down-regulated) significant DEGs from comparison of the S14 vs. S22, S22 vs. S30, and S14 vs. S30 groups, respectively. Gene Ontology enrichment analysis of the DEGs in these salinity comparison groups revealed that the cellular amino acid metabolic process, the regulation of protein processing, the regulation of response to stress, and other terms were significantly enriched. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that nucleotide-binding, oligomerization domain (NOD)-like receptor signaling pathway (ko04621), apoptosis-multiple species (ko04215), Toll and Imd signaling pathway (ko04624), NF-κB signaling pathway (ko04064), apoptosis (ko04210), and focal adhesion (ko04510) were significantly enriched in all salinity comparison groups. qRT-PCR verification of 12 DEGs in the above six pathways was conducted, and the results were consistent with the transcriptome sequencing results in terms of up-regulation and down-regulation, which illustrates that the transcriptome sequencing data are credible. These results were used to preliminarily explore the effects of a sudden drop of salinity on blood physiological and biochemical indexes and immunoregulatory mechanisms of A. kagoshimensis. They also provide a theoretical basis for the selection of bottom areas optimal for release and proliferation of A. kagoshimensis required to restore the declining populations of this species.

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A pipeline to analyse time-course gene expression data

F1000Research ◽

10.12688/f1000research.27262.1 ◽

2020 ◽

Vol 9 ◽

pp. 1447

Author(s):

Nelle Varoquaux ◽

Elizabeth Purdom

Keyword(s):

Gene Expression ◽

Time Course ◽

Phenotypic Diversity ◽

Differential Expression Analysis ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Transcriptomic Data ◽

Environmental Interactions ◽

Time Course Data ◽

Analyse Time

The phenotypic diversity of cells is governed by a complex equilibrium between their genetic identity and their environmental interactions: Understanding the dynamics of gene expression is a fundamental question of biology. However, analysing time-course transcriptomic data raises unique challenging statistical and computational questions, requiring the development of novel methods and software. This workflow provides a step-by-step tutorial of the methodology used to analyse time-course data: (1) quality control and normalization of the dataset; (2) differential expression analysis using functional data analysis; (3) clustering of time-course data; (4) interpreting clusters with GO term and KEGG pathway enrichment analysis. As a case study, we apply this workflow to time-course transcriptomic data from mice exposed to four strains of influenza to showcase every step of the pipeline.

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Transcriptomics Analysis ofCandida albicansTreated with Huanglian Jiedu Decoction Using RNA-seq

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/3198249 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Qianqian Yang ◽

Lei Gao ◽

Maocan Tao ◽

Zhe Chen ◽

Xiaohong Yang ◽

...

Keyword(s):

Gene Expression ◽

Antifungal Agents ◽

Enrichment Analysis ◽

Trichophyton Mentagrophytes ◽

Inhibition Mechanism ◽

Pathway Enrichment Analysis ◽

Rna Seq ◽

Genes Encoding ◽

Life Threatening ◽

Systemic Infections

Candida albicansis the major invasive fungal pathogen of humans, causing diseases ranging from superficial mucosal infections to disseminated, systemic infections that are often life-threatening. Resistance ofC. albicansto antifungal agents and limited antifungal agents has potentially serious implications for management of infections. As a famous multiherb prescription in China, Huanglian Jiedu Decoction (HLJJD,Orengedokutoin Japan) is efficient againstTrichophyton mentagrophytesandC. albicans. But the antifungal mechanism of HLJDD remains unclear. In this study, by using RNA-seq technique, we performed a transcriptomics analysis of gene expression changes forC. albicansunder the treatment of HLJDD. A total of 6057 predicted protein-encoding genes were identified. By gene expression analysis, we obtained a total of 735 differentially expressed genes (DEGs), including 700 upregulated genes and 35 downregulated genes. Genes encoding multidrug transporters such as ABC transporter and MFS transporter were identified to be significantly upregulated. Meanwhile, by pathway enrichment analysis, we identified 26 significant pathways, in which pathways of DNA replication and transporter activity were mainly involved. These results might provide insights for the inhibition mechanism of HLJDD againstC. albicans.

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Novel Biomarker MicroRNAs for Subtyping of Acute Coronary Syndrome: A Bioinformatics Approach

BioMed Research International ◽

10.1155/2016/4618323 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Yujie Zhu ◽

Yuxin Lin ◽

Wenying Yan ◽

Zhandong Sun ◽

Zhi Jiang ◽

...

Keyword(s):

Gene Expression ◽

Acute Coronary Syndrome ◽

Target Genes ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Pathway Enrichment Analysis ◽

Biological Processes ◽

Pathway Enrichment ◽

Coronary Syndrome ◽

Life Threatening

Acute coronary syndrome (ACS) is a life-threatening disease that affects more than half a million people in United States. We currently lack molecular biomarkers to distinguish the unstable angina (UA) and acute myocardial infarction (AMI), which are the two subtypes of ACS. MicroRNAs play significant roles in biological processes and serve as good candidates for biomarkers. In this work, we collected microRNA datasets from the Gene Expression Omnibus database and identified specific microRNAs in different subtypes and universal microRNAs in all subtypes based on our novel network-based bioinformatics approach. These microRNAs were studied for ACS association by pathway enrichment analysis of their target genes. AMI and UA were associated with 27 and 26 microRNAs, respectively, nine of them were detected for both AMI and UA, and five from each subtype had been reported previously. The remaining 22 and 21 microRNAs are novel microRNA biomarkers for AMI and UA, respectively. The findings are then supported by pathway enrichment analysis of the targets of these microRNAs. These novel microRNAs deserve further validation and will be helpful for personalized ACS diagnosis.

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Repeated Sepsis in an 83-Year-Old Man With Cancer With Long-Lasting Invasive Treatments

Case Reports in Clinical Practice ◽

10.18502/crcp.v4i4.2390 ◽

2020 ◽

Author(s):

Masoomeh Imanipour ◽

Nasrin Rasoulzadeh ◽

Amin Hosseini

Keyword(s):

Risk Factors ◽

Immune Response ◽

Immune System ◽

Antibiotic Therapy ◽

Major Trauma ◽

Fluid Replacement ◽

Underlying Condition ◽

Threatening Condition ◽

Life Threatening ◽

Inflammatory Immune Response

Sepsis is a life-threatening condition that arises when the body's response to infection damages its own tissues and organs. Sepsis is caused by an inflammatory immune response triggered by an infection. Its risk factors include aging, weak immune system, major trauma, or burns. Treatment of sepsis is often based on fluid replacement and antibiotic therapy. In this study, an 83-year-old man is reported with two times of diagnosis of sepsis during three years. The first sepsis was due to an infection of the colostomy and the second one followed an infection at tracheostomy site. It seems that the disease and the underlying condition of the patient contribute to the occurrence of sepsis. The patient each time was discharged from the hospital after successful response to the treatment

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Transcriptome deregulation of peripheral monocytes in GBA-related Parkinson's disease

10.1101/2021.12.22.21267952 ◽

2021 ◽

Author(s):

Giulietta Maria Riboldi ◽

Ricardo A Vialle ◽

Elisa Navarro ◽

Evan Udine ◽

Katia de Paiva Lopes ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Membrane Trafficking ◽

Whole Blood ◽

Differential Expression Analysis ◽

Enrichment Analysis ◽

Alpha Synuclein ◽

Ultrastructural Characterization ◽

Gba Gene

Background: Genetic mutations in the beta-glucocerebrosidase (GCase), GBA gene, represent the major genetic risk factor for Parkinson's disease (PD). The function of the GBA gene is at the crossroads between the endo-lysosomal pathway and the immune response, two important mechanisms involved in the pathogenesis of PD. However, modifiers of GBA penetrance have not yet been fully elucidated. Methods: we characterized the transcriptomic profiles of circulating monocytes and whole blood in a population of patients with PD and healthy controls (CTRL) with (PD/GBA and CTRL/GBA) and without GBA variants (iPD and CTRL) (monocytes: n = 56 iPD, 66 CTRL, 23 PD/GBA, 13 CTRL/GBA; whole blood: n = 616 iPD, 362 CTRLs, 127 PD/GBA, 165 CTRL/GBA). Differential expression analysis, pathways enrichment analysis, and outliers detections were performed. Ultrastructural characterization of isolated CD14+ monocytes in the four groups was also performed through electron microscopy. Results: We observed hundreds of differentially expressed genes and dysregulated pathways when comparing manifesting and non-manifesting GBA mutation carriers. Specifically, when compared to idiopathic PD, GBA-PD showed dysregulation in genes involved in alpha-synuclein degradation, aging and amyloid processing (i.e. SNCA, LMNA). Gene-based outlier analysis confirmed the involvement of lysosomal, membrane trafficking, and mitochondrial processing in manifesting compared to nonmanifesting GBA-carriers, as also observed at the ultrastructural levels. Conclusions: Overall, our transcriptomic analysis of primary monocytes identified gene targets and biological processes that can help in understanding the pathogenic mechanisms associated with GBA mutations in the context of PD.

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The epidemiology, clinical presentation, and predictors of severe Tick-borne encephalitis in Lithuania, a highly endemic country: A retrospective study of 1040 patients

PLoS ONE ◽

10.1371/journal.pone.0241587 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0241587

Author(s):

Daiva Radzišauskienė ◽

Jurgita Urbonienė ◽

Gintaras Kaubrys ◽

Saulius Andruškevičius ◽

Dalius Jatužis ◽

...

Keyword(s):

Immune Response ◽

Retrospective Study ◽

Clinical Presentation ◽

Severe Disease ◽

Clinical Manifestations ◽

University Hospital ◽

Disease Course ◽

Tick Borne Encephalitis ◽

Vilnius University ◽

Severity Of The Disease

Introduction In recent decades, the incidence of Tick-borne encephalitis (TBE) has been increasing and posing a growing health problem because of the high costs to the healthcare system and society. The clinical manifestations are well studied but there is a lack of research analyzing the severity of the disease. Objective The aim of this study was to analyze the epidemiology and clinical presentation of severe TBE, to identify the predictors for a severe disease course, and also predictors for meningoencephalomyelitic and severe meningoencephalitic/encephalitic forms. Methods A retrospective study was conducted in the Center of Infectious Diseases and the Center of Neurology at Vilnius University Hospital Santaros Klinikos in the years 2005–2017 to describe the clinical and epidemiological features of TBE in adults. Results 1040 patients were included in the study. A total of 152/1040 (14.6%) patients had a severe course. The highest proportion of severe cases, reaching 41.2%, was reported in the 70–79 year-old age group. A total of 36/152 (23.7%) severe patients presented meningoencephalomyelitis. Myelitic patients were older, were frequently infected in their living areas, and usually reported a monophasic disease course compared with severe meningoencephalitic/encephalitic patients. Severe meningoencephalitic/encephalitic patients, compared with non-severe meningoencephalitic/encephalitic, were older, less often noticed the tick bite, and often had a monophasic course. The sequelae on discharge were observed in 810/1000 (81%) of patients. Conclusions The prognostic factors associated with a severe disease course and severe meningoencephalitic form are: older age, comorbidities, a monophasic course, a fever of 40˚C and above, CRP more than 30 mg/l, CSF protein more than 1 g/l, delayed immune response of TBEV IgG, pathological findings in CT. Age above 60 years, presence of CNS disease, bulbar syndrome, pleocytosis 500x106/l and above, and delayed immune response of TBEV IgG are predictors of the most severe myelitic form.

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