scholarly journals Identification of Novel Gene Expression Patterns and Genetic Mechanisms in Asthma affected Patients Treated with Budesonide

2021 ◽  
Vol 11 (2) ◽  
pp. 555-570
Author(s):  
R. Deepalakshmi ◽  
D. Macrin
Keyword(s):  
Gene Ontology ◽  
Expression Patterns ◽  
Gene Interaction ◽  
Asthma Patient ◽  
Clustering Coefficient ◽  
Computational Pipeline ◽  
Hub Genes ◽  
Asthma Patients ◽  
Genetic Mechanisms ◽  
Upregulated Genes

Aim: To identify the significant genes and pathways involved in asthma patients and asthma-affected patients treated with Budesonide is the aim of our research. Materials and Methods: DNA microarray analysis for asthma has been performed and significant DEGs are identified. Up-regulated genes and down-regulated genes were identified by GEO2R analysis. Gene-Gene interaction was predicted using the STRING. Gene Ontology was analyzed by using the STRING and FunRich. Hub genes were observed by using CytoHubba plugins of Cytoscape. Results: By analyzing GEO2R, 22 genes were upregulated genes and 16 genes were downregulated genes. We have obtained the gene comprising 28 nodes and 8 edges with an estimating clustering coefficient of 0.25 in pHBECs with not treated and pHBECs treated with Budesonide. Gene ontology has shown the 27 genes located in the large intestine as a COSMIC analysis more than other analyses. By using the CytoHubba plugin of Cytoscape, identified MMP3, TSLP, POSTN, ETS1, and SAA1 as hub genes. Conclusion: Due to this limitation, the medications that are brought into the market are not site-directed, and rather they showed random inhibitory actions. So we have developed a computational pipeline to identify the significant novel genes and novel pathways involved in the asthma patient and asthma-affected patient treated with Budesonide.

The Screening and Identification of Key Biomarkers in Adrenocortical Carcinoma: Evidence from a Bioinformatics Analysis

2022 ◽  
Vol 12 (3) ◽  
pp. 523-532
Author(s):  
Xin Yan ◽  
Chunfeng Liang ◽  
Xinghuan Liang ◽  
Li Li ◽  
Zhenxing Huang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gene Ontology ◽  
Protein Interaction ◽  
Adrenocortical Carcinoma ◽  
Gene Expression Omnibus ◽  
Heparin Binding ◽  
Ppi Network ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Upregulated Genes

<sec> <title>Objective:</title> This study aimed to identify the potential key genes associated with the progression and prognosis of adrenocortical carcinoma (ACC). </sec> <sec> <title>Methods:</title> Differentially expressed genes (DEGs) in ACC cells and normal adrenocortical cells were assessed by microarray from the Gene Expression Omnibus database. The biological functions of the classified DEGs were examined by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses and a protein–protein interaction (PPI) network was mapped using Cytoscape software. MCODE software was also used for the module analysis and then 4 algorithms of cytohubba software were used to screen hub genes. The overall survival (OS) examination of the hub genes was then performed by the ualcan online tool. </sec> <sec> <title>Results:</title> Two GSEs (GSE12368, GSE33371) were downloaded from GEO including 18 and 43 cases, respectively. One hundred and sixty-nine DEGs were identified, including 57 upregulated genes and 112 downregulated genes. The Gene Ontology (GO) analyses showed that the upregulated genes were significantly enriched in the mitotic cytokines is, nucleus and ATP binding, while the downregulated genes were involved in the positive regulation of cardiac muscle contraction, extracellular space, and heparin-binding (P < 0.05). The Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) pathway examination showed significant pathways including the cell cycle and the complement and coagulation cascades. The protein– protein interaction (PPI) network consisted of 162 nodes and 847 edges, including mitotic nuclear division, cytoplasmic, protein kinase binding, and cell cycle. All 4 identified hub genes (FOXM1, UBE2C, KIF11, and NDC80) were associated with the prognosis of adrenocortical carcinoma (ACC) by survival analysis. </sec> <sec> <title>Conclusions:</title> The present study offered insights into the molecular mechanism of adrenocortical carcinoma (ACC) that may be beneficial in further analyses. </sec>

scholarly journals Bile Ductal Transcriptome Identifies Key Pathways and Hub Genes in Clonorchis sinensis-Infected Sprague-Dawley Rats

2020 ◽  
Vol 58 (5) ◽  
pp. 513-525
Author(s):  
Won Gi Yoo ◽  
Jung-Mi Kang ◽  
Huong Giang Lê ◽  
Jhang Ho Pak ◽  
Sung-Jong Hong ◽  
...  
Keyword(s):  
Bile Ducts ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Clonorchis Sinensis ◽  
Gene Expression Profiles ◽  
Predictive Biomarkers ◽  
Gene Interaction ◽  
Sprague Dawley ◽  
Hub Genes ◽  
Protein Protein Interaction

Clonorchis sinensis is a food-borne trematode that infects more than 15 million people. The liver fluke causes clonorchiasis and chronical cholangitis, and promotes cholangiocarcinoma. The underlying molecular pathogenesis occurring in the bile duct by the infection is little known. In this study, transcriptome profile in the bile ducts infected with C. sinensis were analyzed using microarray methods. Differentially expressed genes (DEGs) were 1,563 and 1,457 at 2 and 4 weeks after infection. Majority of the DEGs were temporally dysregulated at 2 weeks, but 519 DEGs showed monotonically changing expression patterns that formed seven distinct expression profiles. Protein-protein interaction (PPI) analysis of the DEG products revealed 5 sub-networks and 10 key hub proteins while weighted co-expression network analysis (WGCNA)-derived gene-gene interaction exhibited 16 co-expression modules and 13 key hub genes. The DEGs were significantly enriched in 16 Kyoto Encyclopedia of Genes and Genomes pathways, which were related to original systems, cellular process, environmental information processing, and human diseases. This study uncovered a global picture of gene expression profiles in the bile ducts infected with C. sinensis, and provided a set of potent predictive biomarkers for early diagnosis of clonorchiasis.

scholarly journals Bioinformatics analysis of C3 and CXCR4 demonstrates their potential as prognostic biomarkers in clear cell renal cell carcinoma (ccRCC)

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Quan ◽  
Yuchen Bai ◽  
Yunbei Yang ◽  
Er Lei Han ◽  
Hong Bai ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Therapeutic Targets ◽  
Disease Free Survival ◽  
Prognostic Biomarkers ◽  
Hub Genes ◽  
Cell Renal Cell Carcinoma ◽  
Upregulated Genes

Abstract Background The molecular prognostic biomarkers of clear cell renal cell carcinoma (ccRCC) are still unknown. We aimed at researching the candidate biomarkers and potential therapeutic targets of ccRCC. Methods Three ccRCC expression microarray datasets (include GSE14762, GSE66270 and GSE53757) were downloaded from the gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) between ccRCC and normal tissues were explored. The potential functions of identified DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). And then the protein - protein interaction network (PPI) was established to screen the hub genes. After that, the expressions of hub genes were identified by the oncomine database. The hub genes’ prognostic values of patients with ccRCC were analyzed by GEPIA database. Results A total of 137 DEGs were identified by utilizing the limma package and RRA method, including 63 upregulated genes and 74 downregulated genes. It is found that 137 DEGs were mainly enriched in 82 functional terms and 24 pathways in accordance with the research results. Thirteen highest-scoring genes were screened as hub genes (include 10 upregulated genes and 3 downregulated candidate genes) by utilizing the PPI network and module analysis. Through integrating the oncoming database and GEPIA database, the author found that C3 and CXCR4 are not only overexpressed in ccRCC, but also associated with the prognosis of ccRCC. Further results could reveal that patients with high C3 expression had a poor overall survival (OS), while patients with high CTSS and TLR3 expressions had a good OS; patients with high C3 and CXCR4 expressions had a poor disease-free survival (DFS), while ccRCC patients with high TLR3 expression had a good DFS. Conclusion These findings suggested that C3 and CXCR4 were the candidate biomarkers and potential therapeutic targets of ccRCC patients.

scholarly journals Shared Blood Transcriptomic Signatures between Alzheimer’s Disease and Diabetes Mellitus

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 34
Author(s):  
Taesic Lee ◽  
Hyunju Lee
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interactions ◽  
Expression Patterns ◽  
Protein Protein Interactions ◽  
Hub Genes ◽  
Gene Modules ◽  
Gene Regulatory ◽  
The Brain

Alzheimer’s disease (AD) and diabetes mellitus (DM) are known to have a shared molecular mechanism. We aimed to identify shared blood transcriptomic signatures between AD and DM. Blood expression datasets for each disease were combined and a co-expression network was used to construct modules consisting of genes with similar expression patterns. For each module, a gene regulatory network based on gene expression and protein-protein interactions was established to identify hub genes. We selected one module, where COPS4, PSMA6, GTF2B, GTF2F2, and SSB were identified as dysregulated transcription factors that were common between AD and DM. These five genes were also differentially co-expressed in disease-related tissues, such as the brain in AD and the pancreas in DM. Our study identified gene modules that were dysregulated in both AD and DM blood samples, which may contribute to reveal common pathophysiology between two diseases.

scholarly journals Bioinformatics study on genes related to a high-risk postoperative recurrence of lung adenocarcinoma

2021 ◽  
Vol 104 (3) ◽  
pp. 003685042110180
Author(s):  
Xiao Lin ◽  
Meng Zhou ◽  
Zehong Xu ◽  
Yusheng Chen ◽  
Fan Lin
Keyword(s):  
Cell Cycle ◽  
Gene Ontology ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Candidate Genes ◽  
Postoperative Recurrence ◽  
High Expression ◽  
Ppi Network ◽  
Hub Genes ◽  
Expression Levels

In this study, we aimed to screen out genes associated with a high risk of postoperative recurrence of lung adenocarcinoma and investigate the possible mechanisms of the involvement of these genes in the recurrence of lung adenocarcinoma. We identify Hub genes and verify the expression levels and prognostic roles of these genes. Datasets of GSE40791, GSE31210, and GSE30219 were obtained from the Gene Expression Omnibus database. Enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for the screened candidate genes using the DAVID database. Then, we performed protein–protein interaction (PPI) network analysis through the database STRING. Hub genes were screened out using Cytoscape software, and their expression levels were determined by the GEPIA database. Finally, we assessed the relationships of Hub genes expression levels and the time of survival. Forty-five candidate genes related to a high-risk of lung adenocarcinoma recurrence were screened out. Gene ontology analysis showed that these genes were enriched in the mitotic spindle assembly checkpoint, mitotic sister chromosome segregation, G2/M-phase transition of the mitotic cell cycle, and ATP binding, etc. KEGG analysis showed that these genes were involved predominantly in the cell cycle, p53 signaling pathway, and oocyte meiosis. We screened out the top ten Hub genes related to high expression of lung adenocarcinoma from the PPI network. The high expression levels of eight genes (TOP2A, HMMR, MELK, MAD2L1, BUB1B, BUB1, RRM2, and CCNA2) were related to short recurrence-free survival and they can be used as biomarkers for high risk of lung adenocarcinoma recurrence. This study screened out eight genes associated with a high risk of lung adenocarcinoma recurrence, which might provide novel insights into researching the recurrence mechanisms of lung adenocarcinoma as well as into the selection of targets in the treatment of the disease.

scholarly journals Dynamic Changes of the Anthocyanin Biosynthesis Mechanism During the Development of Heading Chinese Cabbage (Brassica rapa L.) and Arabidopsis Under the Control of BrMYB2

2020 ◽  
Vol 11 ◽  
Author(s):  
Qiong He ◽  
Qianqian Lu ◽  
Yuting He ◽  
Yaxiu Wang ◽  
Ninan Zhang ◽  
...  
Keyword(s):  
Chinese Cabbage ◽  
Anthocyanin Biosynthesis ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Anthocyanin Accumulation ◽  
Total Anthocyanin ◽  
Head Development ◽  
Whole Plant ◽  
Heading Chinese Cabbage ◽  
Upregulated Genes

Chinese cabbage is an important vegetable mainly planted in Asian countries, and mining the molecular mechanism responsible for purple coloration in Brassica crops is fast becoming a research hotspot. In particular, the anthocyanin accumulation characteristic of purple heading Chinese cabbage, along with the plant’s growth and head developing, is still largely unknown. To elucidate the dynamic anthocyanin biosynthesis mechanism of Chinese cabbage during its development processes, here we investigated the expression profiles of 86 anthocyanin biosynthesis genes and corresponding anthocyanin accumulation characteristics of plants as they grew and their heads developed, between purple heading Chinese cabbage 11S91 and its breeding parents. Anthocyanin accumulation of 11S91 increased from the early head formation period onward, whereas the purple trait donor 95T2-5 constantly accumulated anthocyanin throughout its whole plant development. Increasing expression levels of BrMYB2 and BrTT8 together with the downregulation of BrMYBL2.1, BrMYBL2.2, and BrLBD39.1 occurred in both 11S91 and 95T2-5 plants during their growth, accompanied by the significantly continuous upregulation of a phenylpropanoid metabolic gene, BrPAL3.1; a series of early biosynthesis genes, such as BrCHSs, BrCHIs, BrF3Hs, and BrF3’H; as well as some key late biosynthesis genes, such as BrDFR1, BrANS1, BrUF3GT2, BrUF5GT, Br5MAT, and Brp-Cout; in addition to the transport genes BrGST1 and BrGST2. Dynamic expression profiles of these upregulated genes correlated well with the total anthocyanin contents during the processes of plant growth and leaf head development, and results supported by similar evidence for structural genes were also found in the BrMYB2 transgenic Arabidopsis. After intersubspecific hybridization breeding, the purple interior heading leaves of 11S91 inherited the partial purple phenotypes from 95T2-5 while the phenotypes of seedlings and heads were mainly acquired from white 94S17; comparatively in expression patterns of investigated anthocyanin biosynthesis genes, cotyledons of 11S91 might inherit the majority of genetic information from the white type parent, whereas the growth seedlings and developing heading tissues of 11S91 featured expression patterns of these genes more similar to 95T2-5. This comprehensive set of results provides new evidence for a better understanding of the anthocyanin biosynthesis mechanism and future breeding of new purple Brassica vegetables.

Genome-wide screening of m6A-modified transcript in the Wilms’ tumor

2021 ◽  
Author(s):  
Zhuo Liu ◽  
Feng He ◽  
Jing Liu ◽  
Shengrong OuYang ◽  
Zexi Li ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Real Time ◽  
Real Time Pcr ◽  
Wilms Tumor ◽  
Expression Patterns ◽  
Mrna Levels ◽  
Gene Ontology Analysis ◽  
Quantitative Real Time Pcr ◽  
Related Factors ◽  
Significant Difference

Abstract Background Wilms’ tumor, also called nephroblastoma, is the most common pediatric renal malignancy. The pathogenesis of Wilms’ tumor has been attributed to several genetic and epigenetic factors. However, the most pervasive internal mRNA modification that affects almost every process of RNA metabolism, RNA N6-Methyladenosine (m6A) methylation, has not been characterized in Wilms’ tumor. Methods Wilms’ tumor (WT) and adjacent non-cancerous (NC) tissue samples were obtained from 23 children with nephroblastoma, and the global m6A levels were measured by mass spectrometry. Analyses by m6A-mRNA epitranscriptomic microarray and mRNA microarray were performed, and m6A-related mRNAs were validated by quantitative real-time PCR for input and m6A-immunoprecipitated RNA samples from WT and NC tissues. Gene ontology analysis and KEGG pathway analysis were performed for differentially expressed genes, and expression of RNA methylation-related factors was measured by quantitative real-time PCR. Results The total m6A methylation levels in total RNA of WT samples and NC samples were (0.21 ± 0.01)% and (0.22 ± 0.01)%, respectively, with no statistically significant difference. Fifty-nine transcripts were differentially m6A-methylated between the WT and NC groups, which showed distinct m6A modification patterns. Gene ontology analysis indicated that m6A-modified genes were enriched in cancer-associated pathways, including the mTOR pathway, and conjoint analysis of the unique methylation and gene expression patterns in WT samples suggested an association with metabolic pathways.The mRNA levels of the m6A-related “reader” genes, YTHDF1, YTHDF2 and IGF2BP3, were statistically higher in WT samples than in NC samples. Conclusion This is the first study to determine the m6A modification profiles in Wilms’ tumor. Our data provide novel information regarding patterns of m6A modification that correlate with carcinogenesis in Wilms’ tumor.

Identification of Potential Genes Associated with Vemurafenib Efficacy and Melanoma Prognosis

2021 ◽  
Vol 24 ◽  
Author(s):  
Yue Qi ◽  
GuiE Ma
Keyword(s):  
Signaling Pathway ◽  
Estrogen Signaling ◽  
Akt Signaling Pathway ◽  
Ppi Network ◽  
Hub Genes ◽  
Ampk Signaling ◽  
Melanoma Patients ◽  
Key Genes ◽  
Neurotrophin Signaling ◽  
Upregulated Genes

Objective: This work aimed to investigate the molecular mechanisms underlying the efficacy of vemurafenib as a treatment for melanoma. Methods: The GSE52882 dataset, which includes A375 and A2058 melanoma cell lines treated with vemurafenib and dimethyl sulfoxide (DMSO), and clinical information associated with melanoma patients, were acquired from the Gene Expression Omnibus (GEO) database and University of California Santa Cruz (UCSC), respectively. Functional enrichment analysis, protein-protein interaction (PPI) network construction, sub-module analysis, and transcriptional regulation analysis were performed on overlapping differentially expressed genes (DEGs) identified in both cell lines. Finally, we performed a survival analysis based on the genes identified. Results: A total of 447 consistently overlapping DEGs (176 up- and 271 down-regulated DEGs) were screened. Upregulated genes were enriched in pathways of neurotrophin signaling, estrogen signaling, and transcriptional misregulation in cancer. Downregulated DEGs played essential roles in melanogenesis, pathways of cancer, PI3K-Akt signaling pathway, and AMPK signaling pathway. Upregulated (MMP2, JUN, KAT28, and PIK3R3) and downregulated genes (CXCL8, CCND1, IGF1R, and ITGB3) were considered as hub genes in the PPI network. Additionally, PIK3R3 and LEF1 served as key genes in the regulatory network. The overexpression of MMP2 and CXCL8 was associated with a poor prognosis in melanoma patients. Results: A total of 447 consistently overlapping DEGs (176 up- and 271 down-regulated DEGs) were screened. Upregulated genes were enriched in pathways of neurotrophin signaling, estrogen signaling, and transcriptional misregulation in cancer. Downregulated DEGs played essential roles in melanogenesis, pathways of cancer, PI3K-Akt signaling pathway, and AMPK signaling pathway. Upregulated (MMP2, JUN, KAT28, and PIK3R3) and downregulated genes (CXCL8, CCND1, IGF1R, and ITGB3) were considered as hub genes in the PPI network. Additionally, PIK3R3 and LEF1 served as key genes in the regulatory network. The overexpression of MMP2 and CXCL8 was associated with a poor prognosis in melanoma patients. Conclusion: MMP2, CXCL8, PIK3R3, ITGB3, and LEF1 may play roles in the efficacy of vemurafenib treatment in melanoma; for example, MMP2 and PIK3R3 are likely associated with vemurafenib resistance. These findings will contribute to the development of novel therapies for melanoma.

Concerted action of twodlxparalogs in sensory placode formation

Development ◽  
2002 ◽  
Vol 129 (13) ◽  
pp. 3127-3136 ◽  
Author(s):  
Keely S. Solomon ◽  
Andreas Fritz
Keyword(s):  
Target Genes ◽  
Expression Patterns ◽  
Regulatory Control ◽  
Present Evidence ◽  
Genetic Mechanisms ◽  
Dlx Genes ◽  
Functional Reduction ◽  
Sensory Nervous System ◽  
Necessary And Sufficient ◽  
Placode Formation

Sensory placodes are ectodermal thickenings that give rise to elements of the vertebrate cranial sensory nervous system, including the inner ear and nose. Although mutations have been described in humans, mice and zebrafish that perturb ear and nose development, no mutation is known to prevent sensory placode formation. Thus, it has been postulated that a functional redundancy exists in the genetic mechanisms that govern sensory placode development. We describe a zebrafish deletion mutation, b380, which results in a lack of both otic and olfactory placodes.The b380 deletion removes several known genes and expressed sequence tags, including dlx3 and dlx7, two transcription factors that share a homoeobox domain similar in sequence to the Drosophila Distal-less gene. dlx3 and dlx7 are expressed in an overlapping pattern in the regions that produce the otic and olfactory placodes in zebrafish. We present evidence suggesting that it is specifically the removal of these two genes that leads to the otic and olfactory phenotype of b380 mutants. Using morpholinos, antisense oligonucleotides that effectively block translation of target genes, we find that functional reduction of both dlx genes contributes to placode loss. Expression patterns of the otic marker pax2.1, olfactory marker anxV and eya1, a marker of both placodes, in morpholino-injected embryos recapitulate the reduced expression of these genes seen in b380 mutants. We also examine expression of dlx3 and dlx7 in the morpholino-injected embryos and present evidence for existence of auto- and cross-regulatory control of expression among these genes.We demonstrate that dlx3 is necessary and sufficient for proper otic and olfactory placode development. However, our results indicate that dlx3 and dlx7 act in concert and their importance in placode formation is only revealed by inactivating both paralogs.

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