scholarly journals A blood RNA transcriptome signature for COVID-19

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Philip Kam Weng Kwan ◽  
Gail B. Cross ◽  
Claire M. Naftalin ◽  
Bintou A. Ahidjo ◽  
Chee Keng Mok ◽  
...  

Abstract Background COVID-19 is a respiratory viral infection with unique features including a more chronic course and systemic disease manifestations including multiple organ involvement; and there are differences in disease severity between ethnic groups. The immunological basis for disease has not been fully characterised. Analysis of whole-blood RNA expression may provide valuable information on disease pathogenesis. Methods We studied 45 patients with confirmed COVID-19 infection within 10 days from onset of illness and a control group of 19 asymptomatic healthy volunteers with no known exposure to COVID-19 in the previous 14 days. Relevant demographic and clinical information was collected and a blood sample was drawn from all participants for whole-blood RNA sequencing. We evaluated differentially-expressed genes in COVID-19 patients (log2 fold change ≥ 1 versus healthy controls; false-discovery rate < 0.05) and associated protein pathways and compared these to published whole-blood signatures for respiratory syncytial virus (RSV) and influenza. We developed a disease score reflecting the overall magnitude of expression of internally-validated genes and assessed the relationship between the disease score and clinical disease parameters. Results We found 135 differentially-expressed genes in the patients with COVID-19 (median age 35 years; 82% male; 36% Chinese, 53% South Asian ethnicity). Of the 117 induced genes, 14 were found in datasets from RSV and 40 from influenza; 95 genes were unique to COVID-19. Protein pathways were mostly generic responses to viral infections, including apoptosis by P53-associated pathway, but also included some unique pathways such as viral carcinogenesis. There were no major qualitative differences in pathways between ethnic groups. The composite gene-expression score was correlated with the time from onset of symptoms and nasal swab qPCR CT values (both p < 0.01) but was not related to participant age, gender, ethnicity or the presence or absence of chest X-ray abnormalities (all p > 0.05). Conclusions The whole-blood transcriptome of COVID-19 has overall similarity with other respiratory infections but there are some unique pathways that merit further exploration to determine clinical relevance. The approach to a disease score may be of value, but needs further validation in a population with a greater range of disease severity.

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 165-166
Author(s):  
Elisa B Carvalho ◽  
Letícia P Sanglard ◽  
Karolina B Nascimento ◽  
Javier M Meneses ◽  
Daniel R Casagrande ◽  
...  

Abstract Gestating cows have an increased nutrient demand to meet the needs of developing the fetus and the mid-gestation is a critical period for the fetal skeletal muscle development. The aim of this study was to evaluate the skeletal muscle transcriptome in the progeny as a function of the maternal protein nutrition during mid-gestation. Eleven Tabapuã cows and their male calves were used in this study. In the first third of gestation (0 to 100 days of gestation; dg), all cows were kept on pasture. From 100 to 200 dg, the control group (CTRL; 7 animals) received a basal diet achieving 5.5% crude protein (CP), whereas the supplemented group (SUPPL; 4 animals) received a basal diet plus protein supplementation (40% CP). After 200 dg, all animals received the same diet. Weaning was performed at 205 ± 7.5 days of age and animals were kept on pasture until reaching 240 days of age, when they were transferred to a feedlot. Muscle samples were collected at 260 days of age and RNA was extracted for RNA-seq analysis. Gene expression data was analyzed with a negative binomial model to identify (q-value ≤ 0.05) differentially expressed genes (DEG) between treatments. A total of 716 DEG were identified (289 DEG up-regulated and 427 down-regulated in SUPPL group; q-value ≤ 0.05). From the 10 most significant down-regulated DEG in the SUPPL group, two genes associated with apoptotic process were identified: MAPK8IP1 and GRINA, with log2 Fold-Changes (log2FC) of 1.04 and 0.49, respectively. From the 10 most significant up-regulated DEG in the SUPPL group, mTOR was identified, with log2FC=0.31. This is a well-known gene involved in muscle protein synthesis. In conclusion, maternal protein supplementation during mid-gestation affects the expression of genes related to energy metabolism and muscle development, which can lead to long-term impacts on production efficiency.


2009 ◽  
Vol 4 ◽  
pp. BMI.S2530 ◽  
Author(s):  
Salah A. Mohamed ◽  
Hans H. Sievers ◽  
Thorsten Hanke ◽  
Doreen Richardt ◽  
Claudia Schmidtke ◽  
...  

Background Acute aortic dissection (AAD) is a life-threatening condition with high mortality and a relatively unclarified pathophysiological mechanism. Although differentially expressed genes in AAD have been recognized, interactions between these genes remain poorly defined. This study was conducted to gain a better understanding of the molecular mechanisms underlying AAD and to support the future development of a clinical test for monitoring patients at high risk. Materials and Methods Aortic tissue was collected from 19 patients with AAD (mean age 61.7 ± 13.1 years), and from eight other patients (mean age 32.9 ± 12.2 years) who carried the mutated gene for Marfan syndrome (MS). Six patients (mean age 56.7 ± 12.3 years) served as the control group. The PIQOR™ Immunology microarray with 1076 probes in quadruplicates was utilized; the differentially expressed genes were analysed in a MedScan search using PathwayAssist software. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and protein analysis were performed. Results Interactions of MS fibrillin-1 (FBN1) in the MedScan pathway analysis showed four genes, fibulin-1 (FBLN1), fibulin-2 (FBLN2), decorin (DCN) and microfibrillar associated protein 5 (MFAP5), which were differentially expressed in all tissue from AAD. The validation of these genes by qRT-PCR revealed a minimum of three-fold downregulation of FBLN1 (0.5 ± 0.4 vs. 6.1 ± 2.3 fold, p = 0.003) and of DCN (2.5 ± 1.0 vs. 8.5 ± 4.7 fold, p = 0.04) in AAD compared to MS and control samples. Conclusions Downregulation of fibrillin-1 (FBN1) may weaken extracellular components in the aorta and/or interfer with the transmission of cellular signals and eventually cause AAD. Additional research on these four identified genes can be a starting point to develop a diagnostic tool.


2019 ◽  
Author(s):  
De Peng Yuan ◽  
Chong Zhang ◽  
Si Ting Wang ◽  
Yang Liu ◽  
Shuang Li ◽  
...  

Abstract Background: Sheath blight disease (ShB) is one of the important diseases that severely affects rice production. However, the mechanism of defense against ShB remains unclear. To understand the molecular mechanism of rice defense to ShB, an RNA-sequencing analysis was performed using Rhizoctonia solani AG1-IA-inoculated rice leaves. Results: After 48 hours of inoculation, 6,838 genes were differentially expressed in rice leaves (>2 fold, P<0.05). Among them, 3,802 genes were upregulated, while 3,036 were downregulated compared to the control group. In addition, the differentially expressed genes were classified via GO, KEGG, and Mapman analyses. Thirty GO terms, including biological process, molecular function, and cellular component, were significantly enriched, and 30 KEGG pathways included ribosome, carbon metabolism, and biosynthesis of amino acids. A Mapman analysis demonstrated that the phytohormone and metabolic pathways were significantly altered. Interestingly, the expression levels of 359 transcription factors, including WRKY, MYB, and NAC family members, as well as 239 transporter genes, including ABC, MFS, and SWEET, were significantly changed upon R. solani AG1-IA inoculation. An additional genetic study showed that OsWRKY53 negatively and OsAKT1 positively regulate rice defense to R. solani, respectively. In addition, interestingly, many differentially expressed genes contain R. solani-responsive cis-elements in their promoter region. Conclusions: Taken together, our analyses provide valuable information for the additional study of rice defense mechanisms to ShB, and the genes identified could be useful in the future to breed resistant rice.


2020 ◽  
Author(s):  
Yuqing Yang ◽  
Ting Sun ◽  
Chuchen Qiu ◽  
Dongjing Chen ◽  
You Wu

ABSTRACTBackgroundGlioblastoma multiforme (GBM) is a type of high-grade brain tumor known for its proliferative, invasive property, and low survival rate. Recently, with the advancement in therapeutics for tumors such as targeted therapy, individual cancer-specific biomarkers could be recognized as targets for curative purposes. This study identified six differentially expressed genes that have shown significant implications in clinical field, including FPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3. FPR2 was of the same protein family with FPR1, and the latter has been repeatedly reported to promote motility and invasiveness of multiple tumor forms.MethodsThe gene expression profiling of 40 GBM samples and five normal samples from the TCGA database were comprehensively analyzed. The differentially expressed genes (DEGs) were identified using R package and screened by enrichment analysis and examination of protein–protein interaction networks, in order to further explore the functions of DEGs with the highest association with clinical traits and to find hub genes. A qRT-PCR and Western blots were conducted to verify the results of this study.ResultsOur investigation showed that FPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3 were significantly up-regulated in GBM primary tumor compared to the control group. Functional enrichment analysis of the DEGs demonstrated that biological functions related to immune systems, cell division and cell cycle were significantly increased, which were closely related to tumor progression and development. Downstream construction of PPI network analysis indicated that FPR2 was a hub gene involved in high level of interaction with CR3 and VEGFA, which played a key role in inflammatory pathways and cellular dysfunction.ConclusionFPR2, VEGFA, SERPINA1, SOX2, PBK, and ITGB3 were significantly over-expressed in primary tumor samples of GBM patients and were involved in cellular functions and pathways contributing to tumor progression. Out of these six pivotal genes, we intensively focused on FPR2, and our analysis and experimental data both suggested its efficacy as a potential biomarker, serving as an alternative immunotherapeutic target for glioblastoma multiforme.


2021 ◽  
Vol 8 ◽  
Author(s):  
Qingshan Tian ◽  
Hanxiao Niu ◽  
Dingyang Liu ◽  
Na Ta ◽  
Qing Yang ◽  
...  

Long noncoding RNAs have gained widespread attention in recent years for their crucial role in biological regulation. They have been implicated in a range of developmental processes and diseases including cancer, cardiovascular, and neuronal diseases. However, the role of long noncoding RNAs (lncRNAs) in left ventricular noncompaction (LVNC) has not been explored. In this study, we investigated the expression levels of lncRNAs in the blood of LVNC patients and healthy subjects to identify differentially expressed lncRNA that develop LVNC specific biomarkers and targets for developing therapies using biological pathways. We used Agilent Human lncRNA array that contains both updated lncRNAs and mRNAs probes. We identified 1,568 upregulated and 1,141 downregulated (log fold-change &gt; 2.0) lncRNAs that are differentially expressed between LVNC and the control group. Among them, RP11-1100L3.7 and XLOC_002730 are the most upregulated and downregulated lncRNAs. Using quantitative real-time reverse transcription polymerase chain reaction (RT-QPCR), we confirmed the differential expression of three top upregulated and downregulated lncRNAs along with two other randomly picked lncRNAs. Gene Ontology (GO) and KEGG pathways analysis with these differentially expressed lncRNAs provide insight into the cellular pathway leading to LVNC pathogenesis. We also identified 1,066 upregulated and 1,017 downregulated mRNAs. Gene set enrichment analysis (GSEA) showed that G2M, Estrogen, and inflammatory pathways are enriched in differentially expressed genes (DEG). We also identified miRNA targets for these differentially expressed genes. In this study, we first report the use of LncRNA microarray to understand the pathogenesis of LVNC and to identify several lncRNA and genes and their targets as potential biomarkers.


Author(s):  
Shabnam Hashemi ◽  
Seyed Masoud Hosseini ◽  
Arash Ghalyanchilangeroudi ◽  
Nariman Sheikhi

Background and Objectives: Infection with Infectious bronchitis virus (IBV) and avian pathogenic Escherichia coli (APEC) is an important respiratory infection worldwide. Apoptosis is a physiological process of cell death that occurs as part of normal development and responds to a variety of physiological and pathophysiological stimuli. The identification of molecular mechanisms of action or inaction of key apoptotic proteins is important. This study aimed to investigate apoptotic related genes in the trachea tissue of infected (IBV variant 2, and APEC serotype O78: K80) SPF chickens group compared to the control group. Materials and Methods: Forty SPF chickens was divided into 2 groups. Differential transcriptional profile in the infected SPF chickens trachea tissue was compared to those of control group in the early stage of infection by Illumina RNA-seq technique paired-end and strand-specific sequencing. Differentially expressed genes (DEGs) of transcriptome profiling of the trachea from the infected group were identified. Gene ontology category, KEGG pathway, and STRING analysis were analyzed to identify relationships among differentially expressed genes. Results: Twenty-eight apoptotic genes were identified. They consisted of six pathways related to cell death: the extrinsic pathway, intrinsic pathway, endoplasmic reticulum stress pathway, MAPK signaling pathway, and cell death by NFkB and activates mTOR pathway and some regulator and apoptosis inhibitors. Conclusion: All of the apoptotic genes in our study were up-regulated. Among these genes, the more fold change value was for TRADD and BCL2A1 genes, and the less fold change value was for MAP3K14, NFKB1, PIK3CB, and ITPR2 genes.


2020 ◽  
Author(s):  
Man-jin Li ◽  
Ce-jie Lan ◽  
He-ting Gao ◽  
Dan Xing ◽  
Zhen-yu Gu ◽  
...  

Abstract Background: Dengue virus (DENV) is a flavivirus transmitted by mosquitoes that is prevalent in tropical and subtropical countries and has four serotypes (DENV1-4). Aedes aegypti, as the main transmission vector of DENV, exhibits strong infectivity and transmission. With the aim of obtaining a better understanding of the Ae. aegypti-DENV interaction, the transcriptome changes in DENV-2-infected Aag2 cells were studied to describe the immune responses of mosquitoes using the Ae. aegypti Aag2 cell line as a model.Methods: RNAseq technology was used to sequence the transcripts of the Ae. aegypti Aag2 cell line before and after infection with DENV-2. A bioinformatics analysis was then performed to assess the biological functions of the differentially expressed genes, and the sequencing data were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Results: The transcriptome analysis generated 8866 unigenes that were found in both groups, 225 unigenes that were only found in the infection group, and 683 unigenes that only existed in the control group. A total of 1199 differentially expressed genes, including 1014 upregulated and 185 downregulated genes, were identified. The bioinformatics analysis showed that the differentially expressed genes were mainly involved in the longevity regulating pathway, circadian rhythm, DNA replication, and peroxisome, purine, pyrimidine, and drug metabolism. The qRT-PCR verification results showed the same trend, which confirmed that the expression of the differentially expressed genes had changed and that the transcriptome sequencing data were reliable.Conclusions: This study investigated the changes in the transcriptome levels in the DENV-2-infected Ae. aegypti Aag2 cell line, which provides a faster and effective method for discovering genes related to Ae. aegypti pathogen susceptibility. The findings provide basic data and directions for further research on the complex mechanism underlying host-pathogen interactions.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yue Lu ◽  
Yao Qi ◽  
Li Li ◽  
Yuhong Yan ◽  
Danni Yao ◽  
...  

Background. This study aimed to explore the mechanisms of action of the PSORI-CM01 and Yinxieling formulas in the treatment of patients with psoriasis vulgaris by analyzing gene expression in peripheral blood mononuclear cells (PBMCs). Methods. PBMC samples were collected from 21 patients before and after treatment. The study included nine patients in the PSORI-CM01 treatment group, 12 patients in the Yinxieling treatment group, and nine patients in the healthy control group. Gene expression levels in PBMCs were determined using the Affymetrix gene chip technology. Results. In the PSORI-CM01 group before and after treatment, a total of 668 differentially expressed genes were found, of which 445 were upregulated and 223 were downregulated. Before and after Yinxieling treatment, 657 differentially expressed genes were found, of which 168 were upregulated and 489 were downregulated. Venn analysis showed that 78 genes were not differentially expressed in the PSORI-CM01 group and 74 were not differentially expressed in the Yinxieling group compared with those in the controls. Among these genes, 72 genes were common to both groups, which were the genes on which the two drugs acted jointly. The results of KEGG analysis and Venn analysis on the signalling pathways of drug action in treatment groups showed that haemostasis and pathways involving Rho GTPases were common signalling pathways of drug action in the two groups. Conclusions. By a comparative analysis of the treatment groups, we found that both drugs have a positive effect on patients with psoriasis vulgaris, primarily by regulating the pathways related to platelet activation, aggregation, and blood coagulation. Trial registration: ChiCTR, ChiCTR-TRC-14005185, Registered 8 August 2014, http://www.chictr.org.cn/showproj.aspx?proj=4390


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2435-2435
Author(s):  
Delphine Rossille ◽  
Céline Pangault ◽  
Xavier Cahu ◽  
Thierry Lamy ◽  
Burgun Anita ◽  
...  

Abstract Abstract 2435 DLBCLs are the most prevalent lymphomas in adults and great advances have been made in understanding molecular effects on tumor cells as well as tissue environment, leading to determining gene prognosis signatures using transcriptional profiling techniques. As blood cells interact with cells in almost all tissues in the body, blood-derived total RNA gene expressions have been investigated for the past years including for solid cancers [Clin Cancer Res. 2006:3374.], infections [Nature 2010;446:973.] and autoimmune disorders [Genes Immun. 2010;11:269., Immunity 2008;29:150.]. Blood-based microarray approaches were able to identify differentially expressed genes distinguishing patients from healthy volunteers. Interested in the potential of this noninvasive and easy-to-use technique, we hypothesized that aggressive DLBCLs at diagnosis cause molecular perturbations on the whole blood allowing identifying gene expression differentiation compared to healthy controls. Whole blood was collected into PAXgene™ Blood RNA tubes ensuring blood stabilization and sent within 24 hours to be stored at −80°C before extraction. Our study involved high-quality RNA samples from 75 DLBCL patients taken at diagnosis prior to any anti-cancer treatment and 87 healthy volunteers, sex and gender matched. All patients were less than 60 and enrolled in a multicentric & prospective clinical trial for aggressive form of DLBCL, GOELAMS 075, which compares the autologous stem cell treatment to regular R-CHOP procedure. The median age was 52 for patients and 48 for controls. Gene expression profiling (GEP) was assessed using Affymetrix GeneChip® Human Exon 1.0 ST arrays. Unsupervised hierarchical clustering analysis (HCA) distinguished DLBCLs from controls. Two gene lists were identified based on HCA (Figure 1): listA consisted in 3,323 upregulated genes for a subgroup of patients and inversely, listB in 2,966 upregulated genes for controls. Canonical pathways were generated for both lists for genes meeting p<5% and FC >1.2 through the use of IPA (Ingenuity® Systems). The upregulated genes for patients (listA) were found associated with cytokine signaling pathways (Interleukins, NF-κB) while the down-regulated genes (listB) were implicated in T lymphocytes signaling pathways. Further investigations of the dataset by univariate analysis (Mann-Whitney test, FDR<5%, FC >1.5) found 1047 differentially expressed genes, confirming the systemic alteration. A set of 20 genes, selected as the best predictive genes for which the misclassification error rate is minimal, was able to discriminate DLBCLs from control samples (sensitivity= 88% & specificity=95%). No correlation was found between genes and biological parameters such as hemoglobin, leucocytes, lymphocytes, platelets or polynuclear neutrophils. The down-regulated genes were located in the nucleus and involved in transcription deregulation, DNA repair and apoptosis. Upregulated genes were related to the immune response as well as the inflammatory response with for instance S100 proteins which are implicated in myeloid-derived suppressor cell biology. Conclusion: Despite the complex mixture of cell types in blood, whole blood has shown strong systemic perturbations in DLBCLs at diagnosis. Biological investigation indicated an over-expression of the inflammation and immune responses combined to perturbations of the T-lymphocyte pattern. Our findings concerning inflammation-related gene expression including NF-κB activation and upregulated cytokine transcripts, with for instance IL-1, IL-6 & IL-10, invite us to determine whether a specific DLBCL-induced inflammation process exists compared to other nonmalignant diseases [Clin Microbiol Rev. 2002 Jul; 15(3):414-29]. Comparison to other lymphoma and inflammatory diseases as well as with tumor status are under way allowing to better characterizing DLBCL-specific biomarkers. These results shed new lights on DLBCL biology deciphering disease's heterogeneity at the RNA whole blood level. They encourage us to investigate whole blood GEP for prognosis and as a new parameter useful for disease classification. Disclosures: No relevant conflicts of interest to declare.


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