Epigenetically regulated co-expression network of genes significant for rheumatoid arthritis

Epigenomics ◽  
2019 ◽  
Vol 11 (14) ◽  
pp. 1601-1612 ◽  
Author(s):  
Pei He ◽  
Xing-Bo Mo ◽  
Shu-Feng Lei ◽  
Fei-Yan Deng

Aim: To identify epigenetically regulated network of genes in peripheral blood mononuclear cells significant for rheumatoid arthritis (RA). Methods: Differentially expressed genes (DEGs) and their associated differentially expressed miRNAs and differentially methylated positions (DMPs) were identified. Causal inference test (CIT) identified the causal regulation chains. The analyses, for example, weighted gene co-expression network (WGCNA), protein–protein interaction and functional enrichment, evaluated interaction patterns among the DEGs and the associated epigenetic factors. Results: A total of 181 DEGs were identified. The DEGs were significantly regulated by DMPs and/or differentially expressed miRNAs. Causal inference test analyses identified 18 causal chains of DMP-DEG-RA and 16 intermediate DEGs enriched in ‘protein kinase inhibitor activity’. BTN2A1 was co-expressed with other 9 intermediate genes and 11 known RA-associated genes and played a pivotal role in the co-expression network. Conclusion: Epigenetically regulated network of genes in peripheral blood mononuclear cells (PBMC) contributed to RA. The causal DMPs and key intermediate genes may serve as potential biomarkers for RA.

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Jianting Wen ◽  
Jian Liu ◽  
Pingheng Zhang ◽  
Hui Jiang ◽  
Ling Xin ◽  
...  

Abstract Objective: Circular RNAs (circRNAs) are a significant class of molecules involved in a wide range of diverse biological functions that are abnormally expressed in many types of diseases. The present study aimed to determine the circRNAs specifically expressed in peripheral blood mononuclear cells (PBMCs) from rheumatoid arthritis (RA) patients to identify their possible molecular mechanisms. Methods: To identify the circRNAs specifically expressed in RA, we started by sequencing the of PBMCs circRNA and microRNAs (miRNAs) from a RA group (n = 3) and a control group (n = 3). We constructed a network of differentially expressed circRNAs and miRNAs. Then, we selected differentially expressed circRNAs in PBMCs from 10 RA patients relative to 10 age- and sex-matched controls using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Spearman’s correlation test was used to evaluate the correlation of circRNAs with biochemical measurements. Results: A total of 165 circRNAs and 63 miRNAs were differently expressed between RA patients and healthy people according to RNA-seq, including 109 circRNAs that were significantly up-regulated and 56 circRNAs that were down-regulated among the RA patients. RT-qPCR validation demonstrated that the expression levels of hsa_circ_0001200, hsa_circ_0001566, hsa_circ_0003972, and hsa_circ_0008360 were consistent with the results from the sequencing analysis. Then, we found that there were significant correlations between the circRNAs and disease severity. Conclusion: Generally, these results suggest that expression of hsa_circ_0001200, hsa_circ_0001566, hsa_circ_0003972, and hsa_circ_0008360 in PBMCs from RA patients may serve as potential biomarkers for the diagnosis of RA, and these circRNAs may influence the occurrence and development of RA.


Pathogens ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 43
Author(s):  
Lila M. Zarski ◽  
Patty Sue D. Weber ◽  
Yao Lee ◽  
Gisela Soboll Hussey

Equine herpesvirus 1 (EHV-1) affects horses worldwide and causes respiratory disease, abortions, and equine herpesvirus myeloencephalopathy (EHM). Following infection, a cell-associated viremia is established in the peripheral blood mononuclear cells (PBMCs). This viremia is essential for transport of EHV-1 to secondary infection sites where subsequent immunopathology results in diseases such as abortion or EHM. Because of the central role of PBMCs in EHV-1 pathogenesis, our goal was to establish a gene expression analysis of host and equine herpesvirus genes during EHV-1 viremia using RNA sequencing. When comparing transcriptomes of PBMCs during peak viremia to those prior to EHV-1 infection, we found 51 differentially expressed equine genes (48 upregulated and 3 downregulated). After gene ontology analysis, processes such as the interferon defense response, response to chemokines, the complement protein activation cascade, cell adhesion, and coagulation were overrepresented during viremia. Additionally, transcripts for EHV-1, EHV-2, and EHV-5 were identified in pre- and post-EHV-1-infection samples. Looking at micro RNAs (miRNAs), 278 known equine miRNAs and 855 potentially novel equine miRNAs were identified in addition to 57 and 41 potentially novel miRNAs that mapped to the EHV-2 and EHV-5 genomes, respectively. Of those, 1 EHV-5 and 4 equine miRNAs were differentially expressed in PBMCs during viremia. In conclusion, this work expands our current knowledge about the role of PBMCs during EHV-1 viremia and will inform the focus on future experiments to identify host and viral factors that contribute to clinical EHM.


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