Integrative analysis of transcriptome-wide association study data and mRNA expression profiles identified candidate genes and pathways associated with atrial fibrillation

2019 ◽  
Vol 34 (11) ◽  
pp. 1882-1888
Author(s):  
Lu Zhang ◽  
Li Liu ◽  
Mei Ma ◽  
Shiqiang Cheng ◽  
Bolun Cheng ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Association Study ◽  
Mrna Expression ◽  
Candidate Genes ◽  
Expression Profiles ◽  
Study Data ◽  
Integrative Analysis

scholarly journals Integrative Analysis of Transcriptome-Wide Association Study and mRNA Expression Profiles Identifies Candidate Genes Associated With Idiopathic Pulmonary Fibrosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Weiming Gong ◽  
Ping Guo ◽  
Lu Liu ◽  
Qingbo Guan ◽  
Zhongshang Yuan
Keyword(s):  
Association Study ◽  
Mrna Expression ◽  
Candidate Genes ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Pathway Enrichment ◽  
Genome Wide ◽  
Go Terms

Idiopathic pulmonary fibrosis (IPF) is a type of scarring lung disease characterized by a chronic, progressive, and irreversible decline in lung function. The genetic basis of IPF remains elusive. A transcriptome-wide association study (TWAS) of IPF was performed by FUSION using gene expression weights of three tissues combined with a large-scale genome-wide association study (GWAS) dataset, totally involving 2,668 IPF cases and 8,591 controls. Significant genes identified by TWAS were then subjected to gene ontology (GO) and pathway enrichment analysis. The overlapped GO terms and pathways between enrichment analysis of TWAS significant genes and differentially expressed genes (DEGs) from the genome-wide mRNA expression profiling of IPF were also identified. For TWAS significant genes, protein–protein interaction (PPI) network and clustering modules analyses were further conducted using STRING and Cytoscape. Overall, TWAS identified a group of candidate genes for IPF under the Bonferroni corrected P value threshold (0.05/14929 = 3.35 × 10–6), such as DSP (PTWAS = 1.35 × 10–29 for lung tissue), MUC5B (PTWAS = 1.09 × 10–28 for lung tissue), and TOLLIP (PTWAS = 1.41 × 10–15 for whole blood). Pathway enrichment analysis identified multiple candidate pathways, such as herpes simplex infection (P value = 7.93 × 10–5) and antigen processing and presentation (P value = 6.55 × 10–5). 38 common GO terms and 8 KEGG pathways shared by enrichment analysis of TWAS significant genes and DEGs were identified. In the PPI network, 14 genes (DYNLL1, DYNC1LI1, DYNLL2, HLA-DRB5, HLA-DPB1, HLA-DQB2, HLA-DQA2, HLA-DQB1, HLA-DRB1, POLR2L, CENPP, CENPK, NUP133, and NUP107) were simultaneously detected by hub gene and module analysis. In conclusion, through integrative analysis of TWAS and mRNA expression profiles, we identified multiple novel candidate genes, GO terms and pathways for IPF, which contributes to the understanding of the genetic mechanism of IPF.

scholarly journals Integrative Analysis of miRNA and mRNA Expression Profiles in Mammary Glands of Holstein Cows Artificially Infected with Staphylococcus aureus

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 506
Author(s):  
Xiaolong Wang ◽  
Yongliang Fan ◽  
Yifan He ◽  
Ziyin Han ◽  
Zaicheng Gong ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Mrna Expression ◽  
Calcium Binding ◽  
Expression Profiles ◽  
Bovine Mastitis ◽  
Mammary Glands ◽  
Integrative Analysis ◽  
Differentially Expressed ◽  
Future Application ◽  
Collagen Type Iv

Staphylococcus aureus- induced mastitis is one of the most intractable problems for the dairy industry, which causes loss of milk yield and early slaughter of cows worldwide. Few studies have used a comprehensive approach based on the integrative analysis of miRNA and mRNA expression profiles to explore molecular mechanism in bovine mastitis caused by S. aureus. In this study, S. aureus (A1, B1 and C1) and sterile phosphate buffered saline (PBS) (A2, B2 and C2) were introduced to different udder quarters of three individual cows, and transcriptome sequencing and microarrays were utilized to detected miRNA and gene expression in mammary glands from the challenged and control groups. A total of 77 differentially expressed microRNAs (DE miRNAs) and 1625 differentially expressed genes (DEGs) were identified. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that multiple DEGs were enriched in significant terms and pathways associated with immunity and inflammation. Integrative analysis between DE miRNAs and DEGs proved that miR-664b, miR-23b-3p, miR-331-5p, miR-19b and miR-2431-3p were potential factors regulating the expression levels of CD14 Molecule (CD14), G protein subunit gamma 2 (GNG2), interleukin 17A (IL17A), collagen type IV alpha 1 chain (COL4A1), microtubule associated protein RP/EB family member 2 (MAPRE2), member of RAS oncogene family (RAP1B), LDOC1 regulator of NFKB signaling (LDOC1), low-density lipoprotein receptor (LDLR) and S100 calcium binding protein A9 (S100A9) in bovine mastitis caused by S. aureus. These findings could enhance the understanding of the underlying immune response in bovine mammary glands against S. aureus infection and provide a useful foundation for future application of the miRNA–mRNA-based genetic regulatory network in the breeding cows resistant to S. aureus.

scholarly journals Unique MicroRNA and mRNA Interactions in EGFR-Mutated Lung Adenocarcinoma

2018 ◽  
Vol 7 (11) ◽  
pp. 419 ◽  
Author(s):  
Sophia Subat ◽  
Kentaro Inamura ◽  
Hironori Ninomiya ◽  
Hiroko Nagano ◽  
Sakae Okumura ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Mrna Expression ◽  
Regulatory Network ◽  
Egfr Mutation ◽  
Expression Profiles ◽  
Integrative Analysis ◽  
Future Research ◽  
Mutation Status ◽  
Egfr Mutated ◽  
Insight Into

The EGFR gene was one of the first molecules to be selected for targeted gene therapy. EGFR-mutated lung adenocarcinoma, which is responsive to EGFR inhibitors, is characterized by a distinct oncogenic pathway in which unique microRNA (miRNA)–mRNA interactions have been observed. However, little information is available about the miRNA–mRNA regulatory network involved. Both miRNA and mRNA expression profiles were investigated using microarrays in 155 surgically resected specimens of lung adenocarcinoma with a known EGFR mutation status (52 mutated and 103 wild-type cases). An integrative analysis of the data was performed to identify the unique miRNA–mRNA regulatory network in EGFR-mutated lung adenocarcinoma. Expression profiling of miRNAs and mRNAs yielded characteristic miRNA/mRNA signatures (19 miRNAs/431 mRNAs) in EGFR-mutated lung adenocarcinoma. Five of the 19 miRNAs were previously listed as EGFR-mutation-specific miRNAs (i.e., miR-532-3p, miR-500a-3p, miR-224-5p, miR-502-3p, and miR-532-5p). An integrative analysis of miRNA and mRNA expression revealed a refined list of putative miRNA–mRNA interactions, of which 63 were potentially involved in EGFR-mutated tumors. Network structural analysis provided a comprehensive view of the complex miRNA–mRNA interactions in EGFR-mutated lung adenocarcinoma, including DUSP4 and MUC4 axes. Overall, this observational study provides insight into the unique miRNA–mRNA regulatory network present in EGFR-mutated tumors. Our findings, if validated, would inform future research examining the interplay of miRNAs and mRNAs in EGFR-mutated lung adenocarcinoma.

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