scholarly journals Comparative transcriptomics and host-specific parasite gene expression profiles inform on drivers of proliferative kidney disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marc Faber ◽  
Sophie Shaw ◽  
Sohye Yoon ◽  
Eduardo de Paiva Alves ◽  
Bei Wang ◽  
...  

AbstractThe myxozoan parasite, Tetracapsuloidesbryosalmonae has a two-host life cycle alternating between freshwater bryozoans and salmonid fish. Infected fish can develop Proliferative Kidney Disease, characterised by a gross lymphoid-driven kidney pathology in wild and farmed salmonids. To facilitate an in-depth understanding of T.bryosalmonae-host interactions, we have used a two-host parasite transcriptome sequencing approach in generating two parasite transcriptome assemblies; the first derived from parasite spore sacs isolated from infected bryozoans and the second from infected fish kidney tissues. This approach was adopted to minimize host contamination in the absence of a complete T.bryosalmonae genome. Parasite contigs common to both infected hosts (the intersect transcriptome; 7362 contigs) were typically AT-rich (60–75% AT). 5432 contigs within the intersect were annotated. 1930 unannotated contigs encoded for unknown transcripts. We have focused on transcripts encoding proteins involved in; nutrient acquisition, host–parasite interactions, development, cell-to-cell communication and proteins of unknown function, establishing their potential importance in each host by RT-qPCR. Host-specific expression profiles were evident, particularly in transcripts encoding proteases and proteins involved in lipid metabolism, cell adhesion, and development. We confirm for the first time the presence of homeobox proteins and a frizzled homologue in myxozoan parasites. The novel insights into myxozoan biology that this study reveals will help to focus research in developing future disease control strategies.

2020 ◽  
Author(s):  
Marc Faber ◽  
Sohye Yoon ◽  
Sophie Shaw ◽  
Eduardo de Paiva Alves ◽  
Bei Wang ◽  
...  

AbstractThe myxozoan parasite, Tetracapsuloides bryosalmonae has a two-host life cycle alternating between freshwater bryozoans and salmonid fish. Infected fish can develop Proliferative Kidney Disease (PKD), characterised by a gross lymphoid-driven kidney pathology in wild and farmed salmonids. To facilitate an in-depth understanding of T. bryosalmonae-host interactions, we have adopted a two-host parasite transcriptome sequencing approach to minimize host contamination in the absence of a complete T. bryosalmonae genome. Parasite contigs common to both infected hosts (the intersect transcriptome; 7,362 contigs) were typically AT-rich (60-75% AT). 5,432 contigs within the intersect were annotated with 1,930 unannotatde contigs encoding for unknown transcripts. We have focused on transcripts encoding proteins involved in; nutrient acquisition, host-parasite interactions, development, and cell-to-cell communication or proteins of unknown function, establishing their potential importance in each host by RT-qPCR. Host-specific expression profiles were evident, particularly in transcripts encoding proteases and proteins involved in lipid metabolism, cell adhesion, and development. We confirm for the first time the presence of homeobox proteins and a frizzled homologue in myxozoan parasites.The novel insights into myxozoan biology that this study reveals will help to focus research in developing future disease control strategies.


2004 ◽  
Vol 50 (3) ◽  
pp. 490-499 ◽  
Author(s):  
Christian Hafner ◽  
Gerd Schmitz ◽  
Stefanie Meyer ◽  
Frauke Bataille ◽  
Peter Hau ◽  
...  

Abstract Background: Eph receptors and their ligands, the ephrins, represent a large class of cell–cell communication molecules with well-defined developmental functions. Their role in healthy adult tissues and in human disease is still largely unknown, although diverse roles in carcinogenesis have been postulated. Methods: We established a set of fluorescent PCR probes and primers for the definition of individual gene expression profiles of 12 different Eph receptors and 8 ephrins in 13 different healthy tissues. The mRNA expression profiles were studied in human lung, colorectal, kidney, liver, and brain cancers. Results: The family of Eph receptors/ephrins was widely expressed in adult tissues with organ-site-specific patterns: EphB6 was highest in the thymus, compatible with an involvement in T-cell maturation. Brain and testis shared a unique pattern with EphA6, EphA8, and EphB1 being the most prominent. EphA7 had a high abundance in the kidney vasculature. Ephrin-A3 was up-regulated 26-fold in lung cancer, and EphB2 was up-regulated 9-fold in hepatocellular carcinoma. EphA8 was down-regulated in colon cancer, and EphA1/EphA8 was down-regulated in glioblastomas. Conclusion: Eph/Ephrin genes are widely expressed in all adult organs with certain organ-site-specific patterns. Because their function in adult tissues remains unknown, further analysis of their role in disease may disclose new insights beyond their well-defined meaning in development.


Database ◽  
2014 ◽  
Vol 2014 (0) ◽  
pp. bau092-bau092 ◽  
Author(s):  
Q. Zhang ◽  
B. Yang ◽  
X. Chen ◽  
J. Xu ◽  
C. Mei ◽  
...  

2005 ◽  
Vol 21 (3) ◽  
pp. 314-323 ◽  
Author(s):  
Henk P. J. Buermans ◽  
Everaldo M. Redout ◽  
Anja E. Schiel ◽  
René J. P. Musters ◽  
Marian Zuidwijk ◽  
...  

Myocardial right ventricular (RV) hypertrophy due to pulmonary hypertension is aimed at normalizing ventricular wall stress. Depending on the degree of pressure overload, RV hypertrophy may progress to a state of impaired contractile function and heart failure, but this cannot be discerned during the early stages of ventricular remodeling. We tested whether critical differences in gene expression profiles exist between ventricles before the ultimate development of either a compensated or decompensated hypertrophic phenotype. Both phenotypes were selectively induced in Wistar rats by a single subcutaneous injection of either a low or a high dose of the pyrrolizidine alkaloid monocrotaline (MCT). Spotted oligonucleotide microarrays were used to investigate pressure-dependent cardiac gene expression profiles at 2 wk after the MCT injections, between control rats and rats that would ultimately develop either compensated or decompensated hypertrophy. Clustering of significantly regulated genes revealed specific expression profiles for each group, although the degree of hypertrophy was still similar in both. The ventricles destined to progress to failure showed activation of pro-apoptotic pathways, particularly related to mitochondria, whereas the group developing compensated hypertrophy showed blocked pro-death effector signaling via p38-MAPK, through upregulation of MAPK phosphatase-1. In summary, we show that, already at an early time point, pivotal differences in gene expression exist between ventricles that will ultimately develop either a compensated or a decompensated phenotype, depending on the degree of pressure overload. These data reveal genes that may provide markers for the early prediction of clinical outcome as well as potential targets for early intervention.


2016 ◽  
Vol 28 (11) ◽  
pp. 1810 ◽  
Author(s):  
Christina D. Marth ◽  
Neil D. Young ◽  
Lisa Y. Glenton ◽  
Drew M. Noden ◽  
Glenn F. Browning ◽  
...  

The physiological changes associated with the varying hormonal environment throughout the oestrous cycle are linked to the different functions the uterus needs to fulfil. The aim of the present study was to generate global gene expression profiles for the equine uterus during oestrus and Day 5 of dioestrus. To achieve this, samples were collected from five horses during oestrus (follicle >35 mm in diameter) and dioestrus (5 days after ovulation) and analysed using high-throughput RNA sequencing techniques (RNA-Seq). Differentially expressed genes between the two cycle stages were further investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The expression of 1577 genes was found to be significantly upregulated during oestrus, whereas 1864 genes were expressed at significantly higher levels in dioestrus. Most genes upregulated during oestrus were associated with the extracellular matrix, signal interaction and transduction, cell communication or immune function, whereas genes expressed at higher levels in early dioestrus were most commonly associated with metabolic or transport functions, correlating well with the physiological functions of the uterus. These results allow for a more complete understanding of the hormonal influence on gene expression in the equine uterus by functional analysis of up- and downregulated genes in oestrus and dioestrus, respectively. In addition, a valuable baseline is provided for further research, including analyses of changes associated with uterine inflammation.


2019 ◽  
Author(s):  
Billy Zeng ◽  
Benjamin S. Glicksberg ◽  
Patrick Newbury ◽  
Jing Xing ◽  
Ke Liu ◽  
...  

AbstractOne approach to precision medicine is to discover drugs that target molecularly defined diseases. Voluminous cancer patient gene expression profiles have been accumulated in public databases, enabling the creation of a cancer-specific expression signature. By matching this signature to perturbagen-induced gene expression profiles from large drug libraries, researchers can prioritize small molecules that present high potency to reverse expression of signature genes for further experimental testing of their efficacy. This approach has proven to be an efficient and cost-effective way to identify efficacious drug candidates. However, the success of this approach requires multiscale procedures, imposing significant challenges to many labs. Therefore, we present OCTAD: an open workplace for virtually screening compounds targeting precise cancer patient groups using gene expression features. We release OCTAD as a web portal and standalone R workflow to allow experimental and computational scientists to easily navigate the tool. In this work, we describe this tool and demonstrate its potential for precision medicine.


mSystems ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Katie R. Bradwell ◽  
Drissa Coulibaly ◽  
Abdoulaye K. Koné ◽  
Matthew B. Laurens ◽  
Ahmadou Dembélé ◽  
...  

ABSTRACT Children are highly susceptible to clinical malaria, and in regions where malaria is endemic, their immune systems must face successive encounters with Plasmodium falciparum parasites before they develop immunity, first against severe disease and later against uncomplicated malaria. Understanding cellular and molecular interactions between host and parasites during an infection could provide insights into the processes underlying this gradual acquisition of immunity, as well as to how parasites adapt to infect hosts that are successively more malaria experienced. Here, we describe methods to analyze the host and parasite gene expression profiles generated simultaneously from blood samples collected from five consecutive symptomatic P. falciparum infections in three Malian children. We show that the data generated enable statistical assessment of the proportions of (i) each white blood cell subset and (ii) the parasite developmental stages, as well as investigations of host-parasite gene coexpression. We also use the sequences generated to analyze allelic variations in transcribed regions and determine the complexity of each infection. While limited by the modest sample size, our analyses suggest that host gene expression profiles primarily clustered by individual, while the parasite gene expression profiles seemed to differentiate early from late infections. Overall, this study provides a solid framework to examine the mechanisms underlying acquisition of immunity to malaria infections using whole-blood transcriptome sequencing (RNA-seq). IMPORTANCE We show that dual RNA-seq from patient blood samples allows characterization of host/parasite interactions during malaria infections and can provide a solid framework to study the acquisition of antimalarial immunity, as well as the adaptations of P. falciparum to malaria-experienced hosts.


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