scholarly journals Combined Transcriptome and Proteome Leukocyte’s Profiling Reveals Up-Regulated Module of Genes/Proteins Related to Low Density Neutrophils and Impaired Transcription and Translation Processes in Clinical Sepsis

2021 ◽  
Vol 12 ◽  
Author(s):  
Giuseppe Gianini Figueirêdo Leite ◽  
Bianca Lima Ferreira ◽  
Alexandre Keiji Tashima ◽  
Erika Sayuri Nishiduka ◽  
Edecio Cunha-Neto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mononuclear Cells ◽  
Interaction Network ◽  
Low Density ◽  
Mitochondrial Translation ◽  
Peripheral Blood Mononuclear ◽  
Protein Coding ◽  
Protein Protein Interaction ◽  
Network Analyses ◽  
Host Defense System

Sepsis is a global health emergency, which is caused by various sources of infection that lead to changes in gene expression, protein-coding, and metabolism. Advancements in “omics” technologies have provided valuable tools to unravel the mechanisms involved in the pathogenesis of this disease. In this study, we performed shotgun mass spectrometry in peripheral blood mononuclear cells (PBMC) from septic patients (N=24) and healthy controls (N=9) and combined these results with two public microarray leukocytes datasets. Through combination of transcriptome and proteome profiling, we identified 170 co‐differentially expressed genes/proteins. Among these, 122 genes/proteins displayed the same expression trend. Ingenuity Pathway Analysis revealed pathways related to lymphocyte functions with decreased status, and defense processes that were predicted to be strongly increased. Protein-protein interaction network analyses revealed two densely connected regions, which mainly included down‐regulated genes/proteins that were related to the transcription of RNA, translation of proteins, and mitochondrial translation. Additionally, we identified one module comprising of up‐regulated genes/proteins, which were mainly related to low-density neutrophils (LDNs). LDNs were reported in sepsis and in COVID-19. Changes in gene expression level were validated using quantitative real-time PCR in PBMCs from patients with sepsis. To further support that the source of the upregulated module of genes/proteins found in our results were derived from LDNs, we identified an increase of this population by flow cytometry in PBMC samples obtained from the same cohort of septic patients included in the proteomic analysis. This study provides new insights into a reprioritization of biological functions in response to sepsis that involved a transcriptional and translational shutdown of genes/proteins, with exception of a set of genes/proteins related to LDNs and host‐defense system.

scholarly journals Identification of age and ethnicity specific gene expression biomarkers for immune aging

2021 ◽  
Author(s):  
Yang Hu ◽  
Yudai Xu ◽  
Lipeng Mao ◽  
Wen Lei ◽  
Jian Xiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Mononuclear Cells ◽  
Specific Gene ◽  
Human Immune System ◽  
Peripheral Blood Mononuclear ◽  
Network Analyses ◽  
Age Related ◽  
Human Immune ◽  
The Impact

ABSTRACTHuman immune system functions over an entire lifetime, yet how and why the immune system becomes less effective with age are not well understood. Here, we characterize peripheral blood mononuclear cells transcriptome from 172 healthy adults with 21~90 years of age using RNA-seq and the weighted gene correlation network analyses (WGCNA). These data reveal a set of insightful gene expression modules and representative gene biomarkers for human immune system aging from Asian and Caucasian ancestry, respectively. Among them, the aging-specific modules show an age-related gene expression variation spike around early-seventies. In addition, it is not known whether Asian and Caucasian immune systems go through similar gene expression changes throughout their lifespan, and to what extent these aging-associated changes are shared among ethnicities. We find the top hub genes including NUDT7, CLPB, OXNAD1 and MLLT3 are shared between Asian and Caucasian aging related modules and further validated in human PBMCs from different age groups. Overall, the impact of age and race on transcriptional variation elucidated from this study provide insights into the transcriptional driver of immune aging.

scholarly journals QuantSeq. 3′ Sequencing combined with Salmon provides a fast, reliable approach for high throughput RNA expression analysis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Susan M. Corley ◽  
Niamh M. Troy ◽  
Anthony Bosco ◽  
Marc R. Wilkins
Keyword(s):  
Gene Expression ◽  
Mononuclear Cells ◽  
Cost Effective ◽  
Poly I:C ◽  
Rna Seq ◽  
Peripheral Blood Mononuclear ◽  
Protein Coding ◽  
Spearman's Rho ◽  
Spearman’S Rho ◽  
High Consistency

AbstractRNA-Seq is increasingly used for the diagnosis of patients, targeting of therapies and for single cell transcriptomics. These applications require cost effective, fast and reliable ways of capturing and analyzing gene expression data. Here we compared Lexogen’s QuantSeq which captures only the 3′ end of RNA transcripts and Illumina’s TruSeq, using both Tophat2 and Salmon for gene quantification. We also compared these results to microarray. This analysis was performed on peripheral blood mononuclear cells stimulated with Poly (I:C), a viral mimic that induces innate antiviral responses. This provides a well-established model to determine if RNA-Seq and QuantSeq identify the same biological signatures. Gene expression levels in QuantSeq and RNA-Seq were strongly correlated (Spearman’s rho ~0.8), Salmon and Tophat2 (Spearman’s rho > 0.9). There was high consistency in protein coding genes, non-concordant genes had a high proportion of shorter, non-coding features. RNA-Seq identified more differentially expressed genes than QuantSeq, both methods outperformed microarray. The same key biological signals emerged in each of these approaches. We conclude that QuantSeq, coupled with a fast quantification method such as Salmon, should provide a viable alternative to traditional RNA-Seq in many applications and may be of particular value in the study of the 3′UTR region of mRNA.

scholarly journals Identification of key genes associated with multiple sclerosis based on gene expression data from peripheral blood mononuclear cells

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8357 ◽  
Author(s):  
Zhenwei Shang ◽  
Wenjing Sun ◽  
Mingming Zhang ◽  
Lidan Xu ◽  
Xueyuan Jia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Candidate Genes ◽  
Mononuclear Cells ◽  
Biological Processes ◽  
Peripheral Blood Mononuclear ◽  
Protein Protein Interaction ◽  
Microarray Expression ◽  
Disease Pathways ◽  
Combined Data

The aim of this study was to identify the potential key candidate genes of multiple sclerosis (MS) and uncover mechanisms in MS. We combined data from the microarray expression profile of three MS stages and performed bioinformatics analysis. Differentially expressed genes (DEGs) were identified among the distinct stages of MS and healthy controls, and a total of 349 shared DEGs were identified. Gene ontology (GO) and pathway enrichment analyses showed that the DEGs were significantly enriched in the biological processes (BPs) of purine-related metabolic processes and signaling, especially the common DEGs, which were enriched in some immunological processes. Most of the DEGs were enriched in signaling pathways associated with the immune system, some immune diseases and infectious disease pathways. Through a protein–protein interaction (PPI) network analysis and a gene expression regulatory network constructed with MS-related miRNAs, we confirmed FOS, TP53, VEGFA, JUN, HIF1A, RB1, PTGS2, CXCL8, OAS2, NFKBIA and OAS1 as candidate genes of MS. Furthermore , we explored the potential SNPs associated with MS by database mining. In conclusion, this study provides the identified genes, SNPs, biological processes, and cellular pathways associated with MS. The uncovered candidate genes may be potential biomarkers involved in the diagnosis and therapy of MS.

scholarly journals Expression Profiling of Transcriptome and Its Associated Disease Risk in Yang Deficiency Constitution of Healthy Subjects

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ruoxi Yu ◽  
Yin Yang ◽  
Yuanyuan Han ◽  
Pengwei Hou ◽  
Yingshuai Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Healthy Subjects ◽  
Mononuclear Cells ◽  
Clinical Medicine ◽  
Disease Risk ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Evidence ◽  
Chinese Han ◽  
Peripheral Blood Mononuclear

Objectives. Differences among healthy subjects and associated disease risks are of substantial interest in clinical medicine. According to the theory of “constitution-disease correlation” in traditional Chinese medicine, we try to find out if there is any connection between intolerance of cold in Yang deficiency constitution and molecular evidence and if there is any gene expression basis in specific disorders. Methods. Peripheral blood mononuclear cells were collected from Chinese Han individuals with Yang deficiency constitution (n=20) and balanced constitution (n=8) (aged 18–28) and global gene expression profiles were determined between them using the Affymetrix HG-U133 Plus 2.0 array. Results. The results showed that when the fold change was ≥1.2 and q ≤ 0.05, 909 genes were upregulated in the Yang deficiency constitution, while 1189 genes were downregulated. According to our research differential genes found in Yang deficiency constitution were usually related to lower immunity, metabolic disorders, and cancer tendency. Conclusion. Gene expression disturbance exists in Yang deficiency constitution, which corresponds to the concept of constitution and gene classification. It also suggests people with Yang deficiency constitution are susceptible to autoimmune diseases, enteritis, arthritis, metabolism disorders, and cancer, which provides molecular evidence for the theory of “constitution-disease correlation.”

scholarly journals Increased proinflammatory and oxidant gene expression in circulating mononuclear cells in older adults: amelioration by habitual exercise

2011 ◽  
Vol 43 (14) ◽  
pp. 895-902 ◽  
Author(s):  
Lindsey B. Gano ◽  
Anthony J. Donato ◽  
Gary L. Pierce ◽  
Hamza M. Pasha ◽  
Katherine A. Magerko ◽  
...  
Keyword(s):  
Gene Expression ◽  
Older Adults ◽  
Aerobic Exercise ◽  
Exercise Intervention ◽  
Mononuclear Cells ◽  
Maximal Oxygen Consumption ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Maximal Heart Rate ◽  
Peripheral Blood Mononuclear ◽  
Monocyte Chemoattractant Protein 1

We tested the hypothesis that peripheral blood mononuclear cells (PBMC) of older adults demonstrate a proinflammatory/-oxidative gene expression profile that can be improved by regular aerobic exercise. PBMC were isolated from young ( n = 25, 18–33 yr) and middle-aged/older ( n = 40, 50–76 yr) healthy adults. The older adults had greater mRNA expression (real-time RT-PCR) of the proinflammatory/-oxidant transcription factor nuclear factor-κB (1.58-fold, P < 0.05) and receptor for advanced glycation end products (1.12-fold, P < 0.05), the proinflammatory cytokines tumor necrosis factor-α (1.90-fold, P < 0.05) and monocyte chemoattractant protein-1 (1.47-fold, P < 0.05), and the oxidant-producing enzymes nicotinamide adenine dinucleotide phosphate-oxidase (0.91-fold, P < 0.05) and inducible nitric oxide synthase (2.60-fold, P < 0.05). In 11 subjects (58–70 yr), maximal oxygen consumption (+11%) and exercise time (+19%) were increased (both P < 0.001), and expression of the above proinflammatory/-oxidative genes was or tended to be decreased in PBMC after vs. before 2 mo of aerobic exercise (brisk walking ∼6 days/wk, 50 min/day, 70% of maximal heart rate). Expression of interleukin-6 was not different with age or exercise intervention. Age group- and exercise intervention-related differences in gene expression were independent of other factors. PBMC of healthy older adults demonstrate increased expression of several genes associated with inflammation and oxidative stress, which is largely ameliorated by habitual aerobic exercise. This proinflammatory/-oxidative gene signature may represent a therapeutic target for lifestyle and pharmacological prevention and treatment strategies.

scholarly journals Peripheral Blood Gene Expression and IgG Glycosylation Profiles as Markers of Tocilizumab Treatment in Rheumatoid Arthritis

2012 ◽  
Vol 39 (5) ◽  
pp. 916-928 ◽  
Author(s):  
BERTALAN MESKO ◽  
SZILARD POLISKA ◽  
SZILVIA SZAMOSI ◽  
ZOLTAN SZEKANECZ ◽  
JANOS PODANI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Peripheral Blood ◽  
Multiple Testing ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Response To Treatment ◽  
Peripheral Blood Mononuclear ◽  
Gene Sets

Objective.Tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has recently been approved as a biological therapy for rheumatoid arthritis (RA) and other diseases. It is not known if there are characteristic changes in gene expression and immunoglobulin G glycosylation during therapy or in response to treatment.Methods.Global gene expression profiles from peripheral blood mononuclear cells of 13 patients with RA and active disease at Week 0 (baseline) and Week 4 following treatment were obtained together with clinical measures, serum cytokine levels using ELISA, and the degree of galactosylation of the IgG N-glycan chains. Gene sets separating responders and nonresponders were tested using canonical variates analysis. This approach also revealed important gene groups and pathways that differentiate responders from nonresponders.Results.Fifty-nine genes showed significant differences between baseline and Week 4 and thus correlated with treatment. Significantly, 4 genes determined responders after correction for multiple testing. Ten of the 12 genes with the most significant changes were validated using real-time quantitative polymerase chain reaction. An increase in the terminal galactose content of N-linked glycans of IgG was observed in responders versus nonresponders, as well as in treated samples versus samples obtained at baseline.Conclusion.As a preliminary report, gene expression changes as a result of tocilizumab therapy in RA were examined, and gene sets discriminating between responders and nonresponders were found and validated. A significant increase in the degree of galactosylation of IgG N-glycans in patients with RA treated with tocilizumab was documented.

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