scholarly journals Effects of threshold choice on the results of gene expression profiling, using microarray analysis, in a model feeding experiment with rats

2009 ◽  
Vol 52 (1) ◽  
pp. 65-78
Author(s):  
A. Hartmann ◽  
G. Nuernberg ◽  
D. Repsilber ◽  
P. Janczyk ◽  
C. Walz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Microarray Data ◽  
Expression Profiling ◽  
High Reliability ◽  
Food Additives ◽  
Fold Change ◽  
Differentially Expressed ◽  
Biological Processes ◽  
Feeding Experiment

Abstract. Global gene expression studies using microarray technology are widely employed to identify biological processes which are influenced by a treatment e.g. a specific diet. Affected processes are characterized by a significant enrichment of differentially expressed genes (functional annotation analysis). However, different choices of statistical thresholds to select candidates for differential expression will alter the resulting candidates list. This study was conducted to investigate the effect of applying a False Discovery Rate (FDR) correction and different fold change thresholds in statistical analysis of microarray data on diet-affected biological processes based on a significantly increased proportion of differentially expressed genes. In a model feeding experiment with rats fed genetically modified food additives, animals received a supplement of either lyophilized inactivated recombinant VP60 baculovirus (rBV-VP60) or lyophilized inactivated wild type baculovirus (wtBV). Comparative expression profiling was done in spleen, liver and small intestine mucosa. We demonstrated the extent to which threshold choice can affect the biological processes identified as significantly regulated and thus the conclusion drawn from the microarray data. In our study, the combined application of a moderate fold change threshold (FC≥1.5) and a stringent FDR threshold (q≤0.05) exhibited high reliability of biological processes identified as differentially regulated. The application of a stringent FDR threshold of q≤0.05 seems to be an essential prerequisite to reduce considerably the number of false positives. Microarray results of selected differentially expressed molecules were validated successfully by using real-time RT-PCR.

scholarly journals Comparative functional genomic analysis of Alzheimer’s affected and naturally aging brains

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8682
Author(s):  
Yi-Shian Peng ◽  
Chia-Wei Tang ◽  
Yi-Yun Peng ◽  
Hung Chang ◽  
Chien-Lung Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Microarray Data ◽  
Gene List ◽  
Amyloid Β ◽  
Differentially Expressed ◽  
Gene Expression Microarray ◽  
Expression Microarray ◽  
Functional Genomic Analysis ◽  
Gene Expression Microarray Data

Background Alzheimer’s disease (AD) is a prevalent progressive neurodegenerative human disease whose cause remains unclear. Numerous initially highly hopeful anti-AD drugs based on the amyloid-β (Aβ) hypothesis of AD have failed recent late-phase tests. Natural aging (AG) is a high-risk factor for AD. Here, we aim to gain insights in AD that may lead to its novel therapeutic treatment through conducting meta-analyses of gene expression microarray data from AG and AD-affected brain. Methods Five sets of gene expression microarray data from different regions of AD (hereafter, ALZ when referring to data)-affected brain, and one set from AG, were analyzed by means of the application of the methods of differentially expressed genes and differentially co-expressed gene pairs for the identification of putatively disrupted biological pathways and associated abnormal molecular contents. Results Brain-region specificity among ALZ cases and AG-ALZ differences in gene expression and in KEGG pathway disruption were identified. Strong heterogeneity in AD signatures among the five brain regions was observed: HC/PC/SFG showed clear and pronounced AD signatures, MTG moderately so, and EC showed essentially none. There were stark differences between ALZ and AG. OXPHOS and Proteasome were the most disrupted pathways in HC/PC/SFG, while AG showed no OXPHOS disruption and relatively weak Proteasome disruption in AG. Metabolic related pathways including TCA cycle and Pyruvate metabolism were disrupted in ALZ but not in AG. Three pathogenic infection related pathways were disrupted in ALZ. Many cancer and signaling related pathways were shown to be disrupted AG but far less so in ALZ, and not at all in HC. We identified 54 “ALZ-only” differentially expressed genes, all down-regulated and which, when used to augment the gene list of the KEGG AD pathway, made it significantly more AD-specific.

scholarly journals Identification of Differentially Expressed Genes and miRNAs Associated with Esophageal Squamous Cell Carcinoma by Integrated Analysis of Microarray Data

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Lemeng Zhang ◽  
Jianhua Chen ◽  
Tianli Cheng ◽  
Hua Yang ◽  
Changqie Pan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Survival Analysis ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Differentially Expressed Genes ◽  
Microarray Data ◽  
Regulatory Network ◽  
Differentially Expressed ◽  
Pathway Enrichment

To identify candidate key genes and miRNAs associated with esophageal squamous cell carcinoma (ESCC) development and prognosis, the gene expression profiles and miRNA microarray data including GSE20347, GSE38129, GSE23400, and GSE55856 were downloaded from the Gene Expression Omnibus (GEO) database. Clinical and survival data were retrieved from The Cancer Genome Atlas (TCGA). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of differentially expressed genes (DEGs) was analyzed via DAVID, while the DEG-associated protein-protein interaction network (PPI) was constructed using the STRING database. Additionally, the miRNA target gene regulatory network and miRNA coregulatory network were constructed, using the Cytoscape software. Survival analysis and prognostic model construction were performed via the survival (version 2.42-6) and rbsurv R packages, respectively. The results showed a total of 2575, 2111, and 1205 DEGs, and 226 differentially expressed miRNAs (DEMs) were identified. Pathway enrichment analyses revealed that DEGs were mainly enriched in 36 pathways, such as the proteasome, p53, and beta-alanine metabolism pathways. Furthermore, 448 nodes and 1144 interactions were identified in the PPI network, with MYC having the highest random walk score. In addition, 7 DEMs in the microarray data, including miR-196a, miR-21, miR-205, miR-194, miR-103, miR-223, and miR-375, were found in the regulatory network. Moreover, several reported disease-related miRNAs, including miR-198a, miR-103, miR-223, miR-21, miR-194, and miR-375, were found to have common target genes with other DEMs. Survival analysis revealed that 85 DEMs were related to prognosis, among which hsa-miR-1248, hsa-miR-1291, hsa-miR-421, and hsa-miR-7-5p were used for a prognostic survival model. Taken together, this study revealed the important roles of DEGs and DEMs in ESCC development, as well as DEMs in the prognosis of ESCC. This will provide potential therapeutic targets and prognostic predictors for ESCC.

scholarly journals Integrative Analysis of the Genes Induced by the Intestine Microbiota of Infant Born to Term and Breastfed

2020 ◽  
Vol 14 ◽  
pp. 117793222090616
Author(s):  
Badreddine Nouadi ◽  
Yousra Sbaoui ◽  
Mariame El Messal ◽  
Faiza Bennis ◽  
Fatima Chegdani
Keyword(s):  
Gene Expression ◽  
Breast Milk ◽  
Differentially Expressed Genes ◽  
Bacterial Colonization ◽  
Biological Data ◽  
Integrative Analysis ◽  
Differentially Expressed ◽  
Epithelial Tissue ◽  
Biological Processes

Nowadays, the integration of biological data is a major challenge for bioinformatics. Many studies have examined gene expression in the epithelial tissue in the intestines of infants born to term and breastfed, generating a large amount of data. The integration of these data is important to understand the biological processes involved during bacterial colonization of the newborns intestine, particularly through breast milk. This work aims to exploit the bioinformatics approaches, to provide a new representation and interpretation of the interactions between differentially expressed genes in the host intestine induced by the microbiota.

scholarly journals Digital Gene Expression Profiling Analysis of Aged Mice under Moxibustion Treatment

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Nan Liu ◽  
Yunyao Jiang ◽  
Min Xing ◽  
Baixiao Zhao ◽  
Jincai Hou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Ontology ◽  
Gene Expression Profiling ◽  
Differentially Expressed Genes ◽  
Pathway Analysis ◽  
Expression Profiling ◽  
Digital Gene Expression ◽  
Differentially Expressed ◽  
Aged Mice ◽  
Digital Gene Expression Profiling

Aging is closely connected with death, progressive physiological decline, and increased risk of diseases, such as cancer, arteriosclerosis, heart disease, hypertension, and neurodegenerative diseases. It is reported that moxibustion can treat more than 300 kinds of diseases including aging related problems and can improve immune function and physiological functions. The digital gene expression profiling of aged mice with or without moxibustion treatment was investigated and the mechanisms of moxibustion in aged mice were speculated by gene ontology and pathway analysis in the study. Almost 145 million raw reads were obtained by digital gene expression analysis and about 140 million (96.55%) were clean reads. Five differentially expressed genes with an adjusted P value < 0.05 and |log⁡2(fold  change)| > 1 were identified between the control and moxibustion groups. They were Gm6563, Gm8116, Rps26-ps1, Nat8f4, and Igkv3-12. Gene ontology analysis was carried out by the GOseq R package and functional annotations of the differentially expressed genes related to translation, mRNA export from nucleus, mRNA transport, nuclear body, acetyltransferase activity, and so on. Kyoto Encyclopedia of Genes and Genomes database was used for pathway analysis and ribosome was the most significantly enriched pathway term.

Microarray Gene Expression Profiling of B-Cell Chronic Lymphocytic Leukemia Subgroups Defined by Genomic Aberrations and VH Mutation Status

2004 ◽  
Vol 22 (19) ◽  
pp. 3937-3949 ◽  
Author(s):  
Christian Haslinger ◽  
Norbert Schweifer ◽  
Stephan Stilgenbauer ◽  
Hartmut Döhner ◽  
Peter Lichter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Differentially Expressed Genes ◽  
Expression Profiling ◽  
Lymphocytic Leukemia ◽  
Differentially Expressed ◽  
Mutational Status ◽  
Genomic Aberrations ◽  
Cell Chronic Lymphocytic Leukemia

Purpose Genomic aberrations and mutational status of the immunoglobulin variable heavy chain (VH) gene have been shown to be among the most important predictors for outcome in patients with B-cell chronic lymphocytic leukemia (B-CLL). In this study, we report on differential gene expression patterns that are characteristic for genetically defined B-CLL subtypes. Materials and Methods One hundred genetically well-characterized B-CLL samples, together with 11 healthy control samples, were analyzed using oligonucleotide arrays, which test for the expression of some 12,000 human genes. Results Aiming at microarray-based subclassification, class predictors were constructed using sets of differentially expressed genes, which yielded in zero or low misclassification rates. Furthermore, a significant number of the differentially expressed genes clustered in chromosomal regions affected by the respective genomic losses/gains. Deletions affecting chromosome bands 11q22-q23 and 17p13 led to a reduced expression of the corresponding genes, such as ATM and p53, while trisomy 12 resulted in the upregulation of genes mapping to chromosome arm 12q. Using an unsupervised analysis algorithm, expression profiling allowed partitioning into predominantly VH-mutated versus unmutated patient groups; however, association of the expression profile with the VH mutational status could only be detected in male patients. Conclusion The finding that the most significantly differentially expressed genes are located in the corresponding aberrant chromosomal regions indicates that a gene dosage effect may exert a pathogenic role in B-CLL. The significant difference in the partitioning of male and female B-CLL samples suggests that the genomic signature for the VH mutational status might be sex-related.

scholarly journals PO-046 Gene expression profiling of peripheral blood mononuclear cells in young male trampoline athletes

2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Li Gao ◽  
Yong Jie Yang ◽  
En Qi Li ◽  
Jia Ning Mao
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Bone Health ◽  
Expression Profiling ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Signal Pathways ◽  
Healthy Controls ◽  
Mineral Density

Objective Evidence indicates that physical activity influence bone health. However, the molecular mechanisms mediating the beneficial adaptations to exercise are not well understood. The purpose of this study was to examine the differentially expressed genes in PBMC between athletes and healthy controls, and to analyze the important functional genes and signal pathways that cause increased bone mineral density in athletes, in order to further reveal the molecular mechanisms of exercise promoting bone health. Methods Five professional trampoline athletes and five age-matched untrained college students participated in this study. Used the human expression Microarray V4.0 expression profiling chip to detect differentially expressed genes in the two groups, and performed KEGG Pathway analysis and application of STRING database to construct protein interaction Network; Real-Time PCR technology was used to verify the expression of some differential genes.  Results Compared with healthy controls, there were significant improvement in lumbar spine bone mineral density, and 236 up-regulated as well as 265 down-regulated in serum samples of athletes. The differentially expressed genes involved 28 signal pathways, such as cell adhesion molecules. Protein interaction network showed that MYC was at the core node position. Real-time PCR results showed that the expression levels of CD40 and ITGα6 genes in the athletes were up-regulated compared with the healthy controls, the detection results were consistent with that of the gene chip. Conclusions The findings highlight that long-term high-intensity trampoline training could induce transcriptional changes in PBMC of the athletes. These data suggest that gene expression fingerprints can serve as a powerful research tool to design novel strategies for monitoring exercise. The findings of the study also provide support for the notion that PBMC could be used as a substitute to study exercise training that affects bone health.

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