scholarly journals HIV-Associated Neurocognitive Disorder (HAND) Biomarker Identification: Significance Analysis of Microarrays and Two Persuasive Approaches with Random Forest

2020 ◽  
Author(s):  
Hansapani Rodrigo ◽  
Bryan Martinez ◽  
Roberto De La Garza ◽  
Upal Roy
Keyword(s):  
Gene Expression ◽  
White Matter ◽  
Basal Ganglia ◽  
Frontal Cortex ◽  
Differentially Expressed ◽  
Control Group ◽  
Expression Levels ◽  
Significance Analysis ◽  
The Subject ◽  
Gene Expression Levels

Abstract Background: HIV Associated Neurological Disorders (HAND) is relatively common among people with HIV-1 infection, even those taking combined antiretroviral treatment (cART). Genome-wide screening of transcription regulation in brain tissue helps in identifying substantial abnormalities present in patients’ gene transcripts and to discover possible biomarkers for HAND. This study explores the possibility of identifying differentially expressed (DE) genes, which can serve as potential biomarkers to detect HAND. In this study, we have investigated the gene expression levels of three subject groups with different impairment levels of HAND along with a control group in three distinct brain sectors: white matter, frontal cortex, and basal ganglia. Methods: Linear models with weighted least squares along with Benjamini-Hochberg multiple corrections were used to identify DE genes in each brain region. Genes with an adjusted p-value of less than 0.01 were identified as differentially expressed. Principal component analyses (PCA) were performed to detect any groupings among the subject groups. Significance Analysis of Microarrays (SAM) and random forests (RF) methods with two distinct approaches were used to identify DE genes. Results: A total of 710 genes in basal ganglia, 794 genes in the frontal cortex, and 1481 genes in white matter were screened. The highest proportion of DE genes was observed within the two brain regions, frontal neocortex, and basal ganglia. PCA analyses do not exhibit clear groupings among four subject groups. SAM and RF models reveal the genes, CIRBP, RBM3, GPNMB, ISG15, IFIT6, IFI6, and IFIT3, to have DE genes in the frontal cortex or basal ganglia among the subject groups. The gene, GADD45A, a protein-coding gene whose transcript levels tend to increase with stressful growth arrest conditions, was consistently ranked among the top genes by both RF models within the frontal cortex. Conclusions: Our study contributes to a comprehensive understanding of the gene expression levels of the subject with different severity levels of HAND. Several genes that appear to play critical roles in the inflammatory response have been found, and they have an excellent potential to be used as biomarkers to detect HAND under further investigations.

scholarly journals High heterogeneity undermines generalization of differential expression results in RNA-Seq analysis

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Weitong Cui ◽  
Huaru Xue ◽  
Lei Wei ◽  
Jinghua Jin ◽  
Xuewen Tian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Expression ◽  
Small Sample ◽  
Differentially Expressed ◽  
Cancer Type ◽  
Rna Seq ◽  
Sample Sizes ◽  
Large Sample ◽  
Expression Levels ◽  
Gene Expression Levels

Abstract Background RNA sequencing (RNA-Seq) has been widely applied in oncology for monitoring transcriptome changes. However, the emerging problem that high variation of gene expression levels caused by tumor heterogeneity may affect the reproducibility of differential expression (DE) results has rarely been studied. Here, we investigated the reproducibility of DE results for any given number of biological replicates between 3 and 24 and explored why a great many differentially expressed genes (DEGs) were not reproducible. Results Our findings demonstrate that poor reproducibility of DE results exists not only for small sample sizes, but also for relatively large sample sizes. Quite a few of the DEGs detected are specific to the samples in use, rather than genuinely differentially expressed under different conditions. Poor reproducibility of DE results is mainly caused by high variation of gene expression levels for the same gene in different samples. Even though biological variation may account for much of the high variation of gene expression levels, the effect of outlier count data also needs to be treated seriously, as outlier data severely interfere with DE analysis. Conclusions High heterogeneity exists not only in tumor tissue samples of each cancer type studied, but also in normal samples. High heterogeneity leads to poor reproducibility of DEGs, undermining generalization of differential expression results. Therefore, it is necessary to use large sample sizes (at least 10 if possible) in RNA-Seq experimental designs to reduce the impact of biological variability and DE results should be interpreted cautiously unless soundly validated.

scholarly journals Vitronectin and Urokinase-Type Plasminogen Activator Gene Expression Levels Are Increased in Patients with Coronary Artery In-Stent Restenosis

2017 ◽  
Vol 26 (04) ◽  
pp. 218-222
Author(s):  
S. Shafiee ◽  
F. Noorabad-Ghahroodi ◽  
A. Amirfarhangi ◽  
S. Hosseini-Fard ◽  
Z. Sharifi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Coronary Artery ◽  
Plasminogen Activator ◽  
Control Group ◽  
Expression Levels ◽  
Stent Restenosis ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
In Stent Restenosis ◽  
Gene Expression Levels

AbstractNeointimal hyperplasia is known as a main factor contributing to in-stent restenosis (ISR). Monocytes may play a central role in vessel restenosis process after stent implantation. The aim of this study was to investigate the relationships between the urokinase-type plasminogen activator (PLAU) and vitronectin (Vtn) gene expression levels in peripheral blood mononuclear cell samples isolated from whole blood of 66 patients undergoing coronary artery angiography (22 controls, stenosis < 0.05%; 22 with stent no-restenosis and stenosis < 70%; and 22 with ISR and stenosis > 70%). The Vtn and PLAU gene expression levels were measured by real-time quantitative polymerase chain reaction technique. The age- and gender-independent increases in the expression levels of Vtn (17-fold; p < 0.001) and PLAU (27-fold; p < 0.0001) genes were found in the patients with ISR as compared with the control group. The results suggested that the Vtn and PLAU genes may be involved in the coronary artery ISR.

ATF3 and EGR2 gene expression levels in sdLDL-treated macrophages of patients with coronary artery stenosis

2018 ◽  
Vol 42 (1-2) ◽  
pp. 23-29
Author(s):  
Sayed R. Hosseini-Fard ◽  
Mohsen Khosravi ◽  
Amaneh Yarnazari ◽  
Parisa Hassanpour ◽  
Abdollah Amirfarhangi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Coronary Artery ◽  
Cholesterol Metabolism ◽  
Quantitative Polymerase Chain Reaction ◽  
Fold Change ◽  
Expression Level ◽  
Control Group ◽  
Expression Levels ◽  
Vessel Disease ◽  
Gene Expression Levels

AbstractBackground:The metabolism of cholesteryl esters (CEs) is under the control of a gene network in macrophages. Several genes such asATF3andEGR2are related to cholesterol metabolism.Methods:In this study, theATF3andEGR2gene expression levels were evaluated in differentiated macrophages of subjects undergoing coronary artery angiography [controls (<5% stenosis), patients (>70% stenosis)] after treatment with small dense low density lipoprotein (sdLDL) particles. Monocytes were isolated using a RosetteSep Kit and were differentiated into macrophages using the M-CSF factor. A modified heparin-MgSO4-PEG method was used for the sdLDL preparation. TheATF3andEGR2gene expression levels were measured by the real-time quantitative polymerase chain reaction (RT-qPCR) technique.Results:In contrast with the control group (p=0.4), theATF3expression level reduced significantly in the differentiated macrophages from all patients [single vessel disease (SVD), fold change 17 times, p=0.02; two vessel disease (2VD), fold change 1.5 times, p=0.05; three vessel disease (3VD), fold change 3.5 times, p=0.04]. Also, theEGR2expression level reduced significantly in all groups (p<0.02). The gene fold changes had no significant differences between the patients (p>0.8).Conclusions:We propose that the failure ofATF3gene expression improves the CE synthesis after sdLDL influx. Furthermore, the reducedEGR2gene expression level in the sdLDL-treated groups may be a negative factor in cholesterol homeostasis.

scholarly journals Evaluation of UHRF1 and P16INK4A expression levels in newly diagnosed AML patients

2018 ◽  
Vol 5 (9) ◽  
pp. 2658-2663 ◽  
Author(s):  
Vahid Amiri ◽  
Mohamadhossein Mohammadi ◽  
Mohammad Reza Khosravi Farsani ◽  
Arshia Gharehbaghian ◽  
Abbas Hajifathali ◽  
...  
Keyword(s):  
Gene Expression ◽  
Negative Correlation ◽  
Leukemic Cells ◽  
Control Group ◽  
Newly Diagnosed ◽  
Expression Levels ◽  
Age Related ◽  
P16ink4a Gene ◽  
The Impact ◽  
Gene Expression Levels

Introduction: Gene mutation is an infrequent cause of tumor suppressor gene (TSG) defect in de novo AML patients. Instead, it seems that leukemic cells employ epigenetic tricks to attenuate the negative impacts of intact TSGs. Ordinarily, critical TSGs, such as p16INK4A, is hyper-methylated in AML blasts under the impact of master epigenetic regulators, such as UHRF1. In this study, we investigated the correlation between UHRF1 and p16INK4A gene expression levels in newly diagnosed AML patients. Methods: Bone marrow and peripheral blood samples were obtained from 50 newly diagnosed AML patients and 18 healthy normal control subjects. Gene expression levels of UHRF1 and P16INK4A were surveyed using SYBR Green Quantitative Real-time PCR. Statistical analyses were done using SPSS statistical software 21.0. Results: P16INK4A gene expression showed reduced levels in 80.64% of patients above 45 years of age, while only 32% of patients below 45 years had reduced expression levels. The Spearman correlation test also demonstrated a significant negative correlation between UHRF1 and p16INK4A gene expression levels in AML patients, which was not observed in the control group (r=0.343 and P= 0.015). Conclusion: Regarding the age-related patterns of UHRF1 and p16INK4A gene expression, and also the presence of negative correlation between them, we conclude that UHRF1 may potentially be involved in p16INK4A down-regulation in elderly AML patients, which may subsequently facilitate the progression of AML in older ages.  

scholarly journals Propranolol significantly reduced DNA polymerase β expression in patients with essential tremor

2021 ◽  
Vol 40 (3) ◽  
pp. 207-215
Author(s):  
Nefise Kandemir ◽  
Sercan Kenanoglu ◽  
Murat Gultekin ◽  
Nuriye Gokce ◽  
Hilal Akalin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Treatment Group ◽  
Dna Polymerase ◽  
Patient Group ◽  
Control Group ◽  
Expression Levels ◽  
Significant Difference ◽  
Propranolol Treatment ◽  
Pre Treatment ◽  
Gene Expression Levels

Background Essential tremor (ET) is the most common movement disorder. Propranolol is a first-line medication for ET. We aimed to evaluate the effect of propranolol on the expression of poly (ADP-ribose) polymerase 1 (PARP1) and DNA polymerase beta (POLB) genes, which are known to be related to neurodegenerative diseases, in patients with ET. MethodsThirty-five healthy volunteers and thirty-five patients followed up with essential tremors were included in a non-randomized control experimental study. Expressions of PARP1 and POLB genes were compared between the control group and the patient group. In addition, pre- and post-treatment gene expression levels and Fahn-Tolosa-Marin tremor scale values of the patient group were compared after 8 weeks of propranolol treatment. The Wilcoxon rank and Mann Whitney U tests were used to analyze the data. ResultsAt baseline, PARP1 expression was significantly lower in the ET group than in the control group. (p<0.001). POLB gene expression was significantly higher in the pre-treatment ET group than in the controls (p<0.05). There was no significant difference in PARP1 expression levels before and after 8 weeks of propranolol treatment. POLB gene expression was significantly higher in the pre-treatment group than in the post-treatment group (p<0.001). ConclusionPropranolol significantly decreased POLB gene expression but there was no significant difference in PARP1 gene expression levels in the patient group, after 8 weeks of propranolol treatment.

Effects of selenium, zinc, insulin and metallothionein on cadmium-induced oxidative stress and metallothionein gene expression levels in diabetic rats

2020 ◽  
Vol 31 (2) ◽  
Author(s):  
Huseyin Gungor ◽  
Haki Kara
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Diabetic Rats ◽  
Control Group ◽  
Activity Levels ◽  
Sod Activity ◽  
Expression Levels ◽  
Group 6 ◽  
Group 5 ◽  
Gene Expression Levels

AbstractBackgroundThe aim of this study was to investigate the effects of selenium, zinc, insulin, and metallothionein on oxidative damage and metallothionein (MT) gene expression levels in streptozotocin (STZ)-induced type 1 diabetic rats exposed to Cd.MethodsRats were categorized under eight groups (control, STZ, Cd, STZ + Cd, Group 5, Group 6, Group 7, and STZ + Cd + MT [n:8/group]) were used. After diabetes was induced by STZ (55 mg/kg, i.p.), Cd was administered (1 mg/kg CdCl, orally) for 4 weeks. In cadmium-treated groups selenium (Na2SeO3 1.5 mg/kg, i.p.), zinc (ZnSO4 10 mg/kg via oral gavage), insulin (insulin glargine, 2U/day, s.c.), and MT (1mg/kg, every other 10 days, s.c.) were administered. MT gene expression levels, MDA levels, GPx, SOD, and CAT activity levels were determined in liver and kidney tissues.ResultsMT gene expression and MDA levels increased (p < 0.05) while GPx and SOD activity levels decreased (p < 0.05) in STZ, Cd, and STZ + Cd groups. In Group 5, Group 6, Group 7, and Group 8 groups MT gene expression and MDA levels were decreased while GPx and SOD activity levels were increased (p < 0.05). CAT activity significantly increased (p < 0.05) in STZ + Cd group while there were no significance in other groups (p > 0.05). Compared to the control, Group 5, Group 6, Group 7, and Group 8 groups provided no difference for alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and creatinine levels (p > 0.05).ConclusionsOur results suggest that Se, insulin, Zn and MT may have protective effects against hepatotoxicity and nephrotoxicity caused by Cd exposure in diabetic rats by reducing oxidative stress and MT gene expression levels.

The Effects of Amoxicillin, Cefazolin, and Gentamicin Antibiotics on the Antioxidant System in Mouse Heart Tissues

2020 ◽  
Vol 27 (7) ◽  
pp. 614-622
Author(s):  
Ahmet Savcı ◽  
Enver Fehim Koçpınar ◽  
Harun Budak ◽  
Mehmet Çiftci ◽  
Melda Şişecioğlu
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Free Radicals ◽  
Enzyme Activities ◽  
Control Group ◽  
Mouse Heart ◽  
Male Mice ◽  
Expression Levels ◽  
Improper Use ◽  
Gene Expression Levels

Background: Free radicals lead to destruction in various organs of the organism. The improper use of antibiotics increases the formation of free radicals and causes oxidative stress. Objective: In this study, it was aimed to determine the effects of gentamicin, amoxicillin, and cefazolin antibiotics on the mouse heart. Methods: 20 male mice were divided into 4 groups (1st control, 2nd amoxicillin, 3rd cefazolin, and 4th gentamicin groups). The mice in the experimental groups were administered antibiotics intraperitoneally at a dose of 100 mg / kg for 6 days. The control group received normal saline in the same way. The gene expression levels and enzyme activities of SOD, CAT, GPx, GR, GST, and G6PD antioxidant enzymes were investigated. Results : GSH levels decreased in both the amoxicillin and cefazolin groups, while GR, CAT, and SOD enzyme activities increased. In the amoxicillin group, Gr, Gst, Cat, and Sod gene expression levels increased. Conclusion: As a result, it was concluded that amoxicillin and cefazolin caused oxidative stress in the heart, however, gentamicin did not cause any effects.

scholarly journals Transcriptomic Analysis Suggests Genes Expressed Stage-Independently and Stage–Dependently Modulating the Wing Dimorphism of the Brown Planthopper

Genes ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 19 ◽  
Author(s):  
Chao Zhang ◽  
Xiang-Dong Liu
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Brown Planthopper ◽  
Adherens Junction ◽  
Sugar Metabolism ◽  
Differentially Expressed ◽  
Wing Dimorphism ◽  
Expression Levels ◽  
Three Stages ◽  
Gene Expression Levels

Wing dimorphism is considered as an adaptive trait of insects. Brown planthoppers (BPHs) Nilaparvata lugens, a serious pest of rice, are either macropterous or brachypterous. Genetic and environmental factors are both likely to control wing morph determination in BPHs, but the hereditary law and genes network are still unknown. Here, we investigated changes in gene expression levels between macropterous and brachypterous BPHs by creating artificially bred morphotype lines. The nearly pure-bred strains of macropterous and brachypterous BPHs were established, and their transcriptomes and gene expression levels were compared. Over ten-thousand differentially expressed genes (DEGs) between macropterous and brachypterous strains were found in the egg, nymph, and adult stages, and the three stages shared 6523 DEGs. The regulation of actin cytoskeleton, focal adhesion, tight junction, and adherens junction pathways were consistently enriched with DEGs across the three stages, whereas insulin signaling pathway, metabolic pathways, vascular smooth muscle contraction, platelet activation, oxytocin signaling pathway, sugar metabolism, and glycolysis/gluconeogenesis were significantly enriched by DEGs in a specific stage. Gene expression trend profiles across three stages were different between the two strains. Eggs, nymphs, and adults from the macropterous strain were distinguishable from the brachypterous based on gene expression levels, and genes that were related to wing morphs were differentially expressed between wing strains or strain × stage. A proposed mode based on genes and environments to modulate the wing dimorphism of BPHs was provided.

scholarly journals Transcriptome and Small RNA Combined Sequencing Analysis of Cold Tolerance in Non-heading Chinese Cabbage

2021 ◽  
Vol 12 ◽  
Author(s):  
Jin Wang ◽  
Qinxue Zhang ◽  
Xiong You ◽  
Xilin Hou
Keyword(s):  
Gene Expression ◽  
Brassica Rapa ◽  
Small Rna ◽  
Target Genes ◽  
Differentially Expressed ◽  
Sequencing Analysis ◽  
Pak Choi ◽  
Expression Levels ◽  
Heading Chinese Cabbage ◽  
Gene Expression Levels

BackgroundNon-heading Chinese cabbage (Brassica rapa ssp. chinensis) is an important leaf vegetable grown worldwide. However, there has currently been not enough transcriptome and small RNA combined sequencing analysis of cold tolerance, which hinders further functional genomics research.ResultsIn this study, 63.43 Gb of clean data was obtained from the transcriptome analysis. The clean data of each sample reached 6.99 Gb, and the basic percentage of Q30 was 93.68% and above. The clean reads of each sample were sequence aligned with the designated reference genome (Brassica rapa, IVFCAASv1), and the efficiency of the alignment varied from 81.54 to 87.24%. According to the comparison results, 1,860 new genes were discovered in Pak-choi, of which 1,613 were functionally annotated. Among them, 13 common differentially expressed genes were detected in all materials, including seven upregulated and six downregulated. At the same time, we used quantitative real-time PCR to confirm the changes of these gene expression levels. In addition, we sequenced miRNA of the same material. Our findings revealed a total of 34,182,333 small RNA reads, 88,604,604 kinds of small RNAs, among which the most common size was 24 nt. In all materials, the number of common differential miRNAs is eight. According to the corresponding relationship between miRNA and its target genes, we carried out Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis on the set of target genes on each group of differentially expressed miRNAs. Through the analysis, it is found that the distributions of candidate target genes in different materials are different. We not only used transcriptome sequencing and small RNA sequencing but also used experiments to prove the expression levels of differentially expressed genes that were obtained by sequencing. Sequencing combined with experiments proved the mechanism of some differential gene expression levels after low-temperature treatment.ConclusionIn all, this study provides a resource for genetic and genomic research under abiotic stress in Pak-choi.

scholarly journals Evaluation of Selected IL6/STAT3 Pathway Molecules and miRNA Expression in Chronic Obstructive Pulmonary Disease - the Search for New Diagnostic Markers

2021 ◽  
Author(s):  
Justyna Kiszałkiewicz ◽  
Sebastian Majewski ◽  
Wojciech J. Piotrowski ◽  
Paweł Górski ◽  
Dorota Pastuszak-Lewandoska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mirna Expression ◽  
Smoking Status ◽  
Control Group ◽  
Chronic Obstructive ◽  
Tobacco Exposure ◽  
Expression Levels ◽  
Stat3 Pathway ◽  
Global Epidemic ◽  
Gene Expression Levels

Abstract Background COPD has been regarded as a global epidemic due to an increase in pollution and tobacco exposure. Therefore, the study of molecular mechanism as the basis for modern therapy is important. Objective The aim of the study was the assessment of gene expression levels, IL-6, IL-6ST, PIAS3, STAT3, and miRNAs, miR-1, miR-106b, miR-155, in patients with COPD. Methods Induced sputum as well as PBMC were collected from 40 patients clinically verified according to the GOLD 2017 (A-D) classification and from the control group (n = 20). The levels of gene and miRNA expression were analysed by qPCR. Results Statistically significant differences between the study group vs. control group were observed for IL-6 (P = 0.008, Mann-Whitney U test), and miR-155 (P = 0.03, Mann-Whitney U test). There were statistically significant differences between patients: current smokers vs. ex- smokers for STAT3, (P = 0.04, Mann-Whitney U test) and miR-155 (P = 0.03, Mann-Whitney U test) with a higher expression in current smokers. Conclusions Differences in gene expression levels of the IL-6 / gp130 / STAT3 pathway and miRNA depending on the smoking status and classification of patients according to GOLD suggest the importance of these genes in the pathogenesis of COPD and may indicate their potential utility in monitoring the course of the disease.

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