scholarly journals Reanalysis And Integration Of Public Microarray Datasets Reveals Novel Host Genes Modulated In Leprosy

2019 ◽  
Author(s):  
Thyago Leal-Calvo ◽  
Milton Ozório Moraes

AbstractBackgroundLeprosy is an insidious disease caused primarily by mycobacteria. The difficulties in culturing this slow-growing bacteria together with the chronic progression of the disease have hampered the development of accurate methods for diagnosis. Host gene expression profiling is an important tool to assess overall tissue activity, whether in health or disease conditions. High-throughput gene expression experiments have become popular over the last decade or so, and public databases have been created to easily store and retrieve these data. This has enabled researchers to reuse and reanalyze existing datasets with the aim of generating novel and or more robust information. In this work, after a systematic search, nine microarray datasets evaluating host gene expression in leprosy were reanalyzed and the information was integrated to strengthen evidence of differential expression for several genes.ResultsReanalysis of individual datasets revealed several differentially expressed genes (DEGs). Then, five integration methods were tested, both at the P-value and effect size level. In the end, random effects model (REM) and ratio association (sdef) were selected as the main methods to pinpoint DEGs. Overall, some classic gene/pathways were found corroborating previous findings and validating this approach for analysis. Also, various original DEGs related to poorly understood processes in leprosy were described. Nevertheless, some of the novel genes have already been associated with leprosy pathogenesis by genetic or functional studies, whilst others are, as yet, unrelated or poorly studied in these contexts.ConclusionsThis study reinforces evidences of differential expression of several genes and presents novel genes and pathways associated with leprosy pathogenesis. Altogether, these data are useful in better understanding host responses to the disease and, at the same time, provide a list of potential host biomarkers that could be useful in complementing leprosy diagnosis based on transcriptional levels.

2018 ◽  
Vol 2 (2) ◽  
pp. 151-163 ◽  
Author(s):  
Wayne A. Warner ◽  
David H. Spencer ◽  
Maria Trissal ◽  
Brian S. White ◽  
Nichole Helton ◽  
...  

Key Points A subset of snoRNAs is expressed in a developmental- and lineage-specific manner during human hematopoiesis. Neither host gene expression nor alternative splicing accounted for the observed differential expression of snoRNAs in a subset of AML.


Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1431 ◽  
Author(s):  
Yvonne Drechsler ◽  
Elton J. R. Vasconcelos ◽  
Lisa M. Griggs ◽  
Pedro P. P. V. Diniz ◽  
Ellen Collisson

Feline coronavirus is a highly contagious virus potentially resulting in feline infectious peritonitis (FIP), while the pathogenesis of FIP remains not well understood, particularly in the events leading to the disease. A predominant theory is that the pathogenic FIPV arises from a mutation, so that it could replicate not only in enterocytes of the intestines but also in monocytes, subsequently systemically transporting the virus. The immune status and genetics of affected cats certainly play an important role in the pathogenesis. Considering the importance of genetics and host immune responses in viral infections, the goal of this study was to elucidate host gene expression in macrophages using RNA sequencing. Macrophages from healthy male cats infected with FIPV 79-1146 ex vivo displayed a differential host gene expression. Despite the virus uptake, aligned viral reads did not increase from 2 to 17 h. The overlap of host gene expression among macrophages from different cats was limited, even though viral transcripts were detected in the cells. Interestingly, some of the downregulated genes in all macrophages were involved in immune signaling, while some upregulated genes common for all cats were found to be inhibiting immune activation. Our results highlight individual host responses playing an important role, consistent with the fact that few cats develop feline infectious peritonitis despite a common presence of enteric FCoV.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhang-Wei Liu ◽  
Nan Zhao ◽  
Yin-Na Su ◽  
Shan-Shan Chen ◽  
Xin-Jian He

An amendment to this paper has been published and can be accessed via a link at the top of the paper.


1990 ◽  
pp. 701-708 ◽  
Author(s):  
C. Sengupta-Gopalan ◽  
E. Estabrook ◽  
H. Gambliel ◽  
W. Nirunsuksiri ◽  
H. Richter

mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Lauren E. Fuess ◽  
Stijn den Haan ◽  
Fei Ling ◽  
Jesse N. Weber ◽  
Natalie C. Steinel ◽  
...  

ABSTRACT Commensal microbial communities have immense effects on their vertebrate hosts, contributing to a number of physiological functions, as well as host fitness. In particular, host immunity is strongly linked to microbiota composition through poorly understood bi-directional links. Gene expression may be a potential mediator of these links between microbial communities and host function. However, few studies have investigated connections between microbiota composition and expression of host immune genes in complex systems. Here, we leverage a large study of laboratory-raised fish from the species Gasterosteus aculeatus (three-spined stickleback) to document correlations between gene expression and microbiome composition. First, we examined correlations between microbiome alpha diversity and gene expression. Our results demonstrate robust positive associations between microbial alpha diversity and expression of host immune genes. Next, we examined correlations between host gene expression and abundance of microbial taxa. We identified 15 microbial families that were highly correlated with host gene expression. These families were all tightly correlated with host expression of immune genes and processes, falling into one of three categories—those positively correlated, negatively correlated, and neutrally related to immune processes. Furthermore, we highlight several important immune processes that are commonly associated with the abundance of these taxa, including both macrophage and B cell functions. Further functional characterization of microbial taxa will help disentangle the mechanisms of the correlations described here. In sum, our study supports prevailing hypotheses of intimate links between host immunity and gut microbiome composition. IMPORTANCE Here, we document associations between host gene expression and gut microbiome composition in a nonmammalian vertebrate species. We highlight associations between expression of immune genes and both microbiome diversity and abundance of specific microbial taxa. These findings support other findings from model systems which have suggested that gut microbiome composition and host immunity are intimately linked. Furthermore, we demonstrate that these correlations are truly systemic; the gene expression detailed here was collected from an important fish immune organ (the head kidney) that is anatomically distant from the gut. This emphasizes the systemic impact of connections between gut microbiota and host immune function. Our work is a significant advancement in the understanding of immune-microbiome links in nonmodel, natural systems.


2011 ◽  
Vol 140 (5) ◽  
pp. S-663 ◽  
Author(s):  
Guillaume Dalmasso ◽  
Hang Thi Thu Nguyen ◽  
Yutao Yan ◽  
Hamed Laroui ◽  
Moiz A. Charania ◽  
...  

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Andreas W Heumüller ◽  
Jes-Niels Boeckel ◽  
Nicolas Jaé ◽  
Yuliya Ponomareva ◽  
Wei Chen ◽  
...  

Circular RNAs (circRNAs) are non-coding RNAs generated by back-splicing. Back-splicing has been considered as a rare event, but circRNAs were recently found to be abundantly expressed among a variety of human cells and tissues. Nevertheless, the expressional regulation, processing and biological functions of circRNAs are largely unknown. Cytoplasmic circRNAs can bind and trap microRNAs, whereas nuclear circRNAs may affect host gene expression. However, the expression, regulation and functions of circRNAs in endothelial cells have not been determined so far. In this study, basal expression and regulation of circRNAs by hypoxia in human umbilical endothelial cells (HUVEC) were analyzed using deep sequencing. Among the identified 7,388 circRNAs, 2,875 had not been annotated before. We further validated the expression of 40 selected circRNAs by RT-PCR and found that the majority is resistant to RNase R digestion, lacks polyadenylation and is localized to the cytoplasm. Cloning and subsequent sequencing validated the newly generated back splice sites for selected circRNAs. Furthermore, analysis of RNA-seq data revealed that circRNAs, particularly the cytoplasmatic circular RNA cZNF292, are significantly regulated by hypoxia in HUVECs. The siRNA-mediated knockdown of HIF-1α had no effect on cZNF292 induction under hypoxia, suggesting a HIF-1α independent regulation. Most importantly, siRNA-mediated knockdown of cZNF292 significantly reduced spheroid sprouting and network formation of endothelial cells. Furthermore, knockdown of cZNF292 had no effect on its host gene expression. Exon array analysis after cZNF292 knockdown revealed a significant expressional upregulation of 167 as well as a significant expressional downregulation of 123 genes of which most were associated with metabolic processes according to GO annotation. Analysis of Ago-HITS-CLIP data revealed no putative miR-binding sites, suggesting that cZNF292 does not act as a miR-sponge. Taken together, we show for the first time the expression, regulation and function of circRNAs in endothelial cells. The circRNA cZNF292 is regulated by hypoxia and has an important angiogenic function in endothelial cells.


Data in Brief ◽  
2020 ◽  
Vol 32 ◽  
pp. 106207 ◽  
Author(s):  
Rahila Sardar ◽  
Deepshikha Satish ◽  
Shweta Birla ◽  
Dinesh Gupta

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