Ontology highlight
ABSTRACT:
PROVIDER: PRJNA398415 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5941020_1.fastq.gz | Fastqsanger.gz | |||
| SRR5941020_2.fastq.gz | Fastqsanger.gz | |||
| SRR5941030_1.fastq.gz | Fastqsanger.gz | |||
| SRR5941030_2.fastq.gz | Fastqsanger.gz | |||
| SRR5941040_1.fastq.gz | Fastqsanger.gz |
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Project description:Host immune responses during late-onset sepsis (LOS) in very preterm infants are poorly characterised due to a complex and dynamic pathophysiology and challenges in working with small available blood volumes. We present here an unbiased transcriptomic analysis of whole peripheral blood from very preterm infants at the time of LOS. RNA-Seq was performed on peripheral blood samples (6 – 29 days postnatal age) taken at the time of suspected LOS from very preterm infants <30 weeks gestational age. Infants were classified based on blood culture positivity and elevated C-reactive protein concentrations as having confirmed LOS (n=5), possible LOS (n=4) or no LOS (n=9). Bioinformatics and statistical analyses performed included pathway over-representation and protein-protein interaction network analyses. Plasma cytokine immunoassays were performed to validate differentially expressed cytokine pathways.The blood leukocyte transcriptional responses of infants with confirmed LOS differed significantly from infants without LOS (1,317 differentially expressed genes). However, infants with possible LOS could not be distinguished from infants with no LOS or confirmed LOS. Transcriptional alterations associated with LOS included genes involved in pathogen recognition (mainly TLR pathways), cytokine signalling (both pro-inflammatory and inhibitory responses), immune and haematological regulation (including cell death pathways), and metabolism (altered cholesterol biosynthesis). At the transcriptional-level cytokine responses during LOS were characterised by over-representation of IFN-α/β, IFN-γ, IL-1 and IL-6 signalling pathways and up-regulation of genes for inflammatory responses. Infants with confirmed LOS had significantly higher levels of IL-1α and IL-6 in their plasma. Blood responses in very preterm infants with LOS are characterised by altered host immune responses that appear to reflect unbalanced immuno-metabolic homeostasis.
2020-06-03 | GSE138712 | GEO
Project description:The use of assisted reproductive technologies (ART) can induce a congenital overgrowth condition in humans and ruminants, namely Beckwith-Wiedemann syndrome (BWS) and large offspring syndrome (LOS), respectively. Shared phenotypes and epigenotypes have been found between BWS and LOS. We have observed global misregulation of transcripts in bovine foetuses with LOS. microRNAs (miRNAs) are important post-transcriptional gene expression regulators. We hypothesize that there is miRNA misregulation in LOS and that this misregulation is shared with BWS. In this study, small RNA sequencing was conducted to investigate miRNA expression profiles in bovine and human samples. We detected 407 abundant known miRNAs and predicted 196 putative miRNAs from the bovine sequencing results and identified 505 abundant miRNAs in human tongue. Differentially expressed miRNAs (DE-miRNAs) were identified between control and LOS groups in all tissues analysed as well as between BWS and control human samples. DE-miRNAs were detected from several miRNA clusters including DLK1-DIO3 genomic imprinted cluster in LOS and BWS. DNA hypermethylation was associated with downregulation of miRNAs in the DLK1-DIO3. mRNA targets of the DE-miRNAs were predicted and signalling pathways associated with control of organ size (including the Hippo signalling pathway), cell proliferation, apoptosis, cell survival, cell cycle, and cell adhesion were found to be enriched with these genes. Yes associated protein 1 (YAP1) is the core effector of the Hippo signalling pathway, and increased level of active (non-phosphorylated) YAP1 protein was detected in skeletal muscle of LOS foetuses. Overall, our data provide evidence of miRNA misregulation in LOS and BWS.
2019-07-30 | GSE117015 | GEO
Project description:Large offspring syndrome (LOS) and Beckwith-Wiedemann syndrome are a similar epigenetic congenital overgrowth conditions in ruminants and humans, respectively. We have reported global loss-of-imprinting, methylome epimutations, and global misregulation of genes in LOS. However, less than 4% of gene misregulation can be explained with short range (<20Kb) alterations in DNA methylation. Therefore, we hypothesized that methylome epimutations in LOS affect chromosome architecture which results in misregulation of genes located at distances >20Kb in cis and also in trans (other chromosomes). Our analyses focused on two imprinted domains that frequently show misregulation in these syndromes, namely KvDMR1 and IGF2R. Using bovine fetal fibroblasts, we identified CTCF binding at IGF2R but not KvDMR1, and allele-specific chromosome architecture of these domains in controls. In LOS, analyses identified erroneous long-range contacts and clustering tendency in the direction of expression of misregulated genes. In conclusion, altered chromosome architecture is involved in the etiology of LOS.
2022-04-22 | GSE197128 | GEO
Project description:Large/abnormal offspring syndrome (LOS/AOS) is a congenital overgrowth syndrome reported in ruminants produced by assisted reproduction (ART-LOS) which exhibit global disruption of the epigenome and transcriptome. LOS/AOS shares phenotypes and epigenotypes with the human congenital overgrowth condition Beckwith-Wiedemann syndrome. We have reported that LOS occurs spontaneously (SLOS), however, to date, no study has been conducted to determine if SLOS has the same methylome epimutations as ART-LOS. In this study, we performed whole genome bisulfite sequencing to examine global DNA methylation in SLOS and ART-LOS tissues. We observed unique patterns of global distribution of differentially methylated regions (DMRs) over different genomic contexts, such as promoters, CpG islands and surrounding regions, and repetitive sequences from different treatment groups. In addition, we identified hundreds of LOS-vulnerable DMRs across different cattle breeds when analyzing four idependent LOS experiments together. Specifically, there are 25 highly vulnerable DMRs that could potentially serve as molecular markers for the diagnosis of LOS, including at the promoters of DMRT2 and TBX18, at the imprinted gene bodies of IGF2R, PRDM8, and BLCAP/NNAT, and at multiple CpG islands. We also observed tissue-specific DNA methylation patterns between muscle and blood, and conservation of ART-induced DNA methylation changes between muscle and blood. We conclude that as in ART-LOS, alterations of the epigenome are involved in the etiology of SLOS. In addition, SLOS and ART-LOS share some similarities in methylome epimutations.
2022-05-03 | GSE199084 | GEO
Project description:Purpose: The recent publication of the fungal mutualist R. irregularis genome facilitated transcriptomic studies. We here adress the gene regulation of R. irregularis in response to root exudates from rice wild-type and osnope1 (no perception candidate - mutant unable to host arbuscular mycorrhizal fungi) Methods: Spores of R. irregularis were treated with root exudates and collected at 1 hour, 24 hours and 7 days after addition. To monitor fungal gene regulation, control conditions were also prepared at T0, 1h, 24h and 7d. mRNA were sequenced by HiSeq Illumina. Reads were mapped on the Rhizophagus irregularis genome assembly (Gloin1 - Tisserant et al., PNAS, 2013) using CLCworkbench suite. Results: -At 1h, a set of 92 fungal genes were found up-regulated in response to wt root exudates (92), not to osnope1 root exudates, many of them being involved in cell signaling. -At 24h and 7d, numerous genes putatively involved in primary metabolism were up-regulated in response to wt root exudates, not in response to osnope1 root exudates -Several vital genes involved in cell development are repressed in response to osnope1 RE compared to wt RE. Conclusions: these results argue for a high metabolic activity induced by wt root exudates, not by osnope1 root exudates.
2017-02-04 | GSE65595 | GEO
Project description:In vitro production of bovine embryos can result in large/abnormal offspring syndrome (LOS), a condition characterized by macrosomia, macroglossia, exomphalos and placental abnormalities. LOS can lead to the death of dam and calf. Currently, no test exists to identify LOS pregnancies. We hypothesized that maternal blood markers are useful to identify LOS. Bovine fetuses were generated by artificial insemination (control) or produced in vitro. Surgical fetal collections performed on d56 or d105. Maternal blood was collected on gestation d55 and d105. On d56 and d105, fetuses produced in vitro weighing greater than 97th percentile of the AI weight were considered as LOS. To determine whether maternal blood may be used to identify LOS on d55 and/or d105 of gestation, leukocyte mRNA from 23 pregnant females was isolated and sequenced using a short-read platform. Unsupervised clustering grouped 20 samples by animal (n=10 heifers) rather than by stage of pregnancy. Leukocyte gene expression analyses revealed >3,500 differentially expressed genes in females carrying the two largest LOS fetuses. In summary, our study suggests that transcript amount of ATF7IP from d105 maternal leukocytes may be useful to identify extreme cases of LOS.
2022-06-29 | GSE179946 | GEO
Project description:The plant fungal pathogen Fusarium graminearum which has part of its life cycle in the soil generally comes in contact with bacteria. Therefore the fungus was used as fungal model to test fungal responses to bacterial presence and ascertain the presence of an innate immune system in fungi through a transcriptomics study. Bacterial presence was established by exposing young fungal cultures to the well characterised MAMPs (Microbe Associated Molecular Pattern) such as Flagellin (FLG), Lipooligosacharides (LOS) and Peptidoglycans (PGN) and water was used as the control. The results showed that the fungus reacts to the presence of MAMPs within hours and that the 3 MAMPs up-regulated a set of common genes. These significantly up-regulated common genes can be classified into categories such as energy generation, amino acid metabolism, iron uptake, secondary metabolism and transporters related to secondary metabolism. Analysis of the transcriptional reponse from FLG showed that the MAMP which was obtained comercially was blended with sucrose and this was later confirmed by the commercial provider.
2016-06-02 | GSE65311 | GEO
Project description:Embryos generated with the use of assisted reproductive technologies (ART) can develop overgrowth syndromes. In ruminants, the condition is referred to as large offspring syndrome (LOS) and exhibits variable phenotypic abnormalities including overgrowth, enlarged tongue, and abdominal wall defects. These characteristics recapitulate those observed in the human loss-of-imprinting (LOI) overgrowth syndrome Beckwith-Wiedemann (BWS). We have recently shown LOI at the KCNQ1 locus in LOS, the most common epimutation in BWS. Although the first case of ART-induced LOS was reported in 1995, studies have not yet determined the extent of LOI in this condition. Here, we determined allele-specific expression of imprinted genes previously identified in human and/or mouse in day 105 Bos taurus indicus X Bos taurus taurus F1 hybrid control and LOS fetuses using RNAseq. Our analysis allowed us to determine the monoallelic expression of 20 genes in tissues of control fetuses. LOS fetuses displayed variable LOI when compared to controls. Biallelic expression of imprinted genes in LOS was associated with tissue-specific hypomethylation of the normally methylated parental allele. In addition, a positive correlation was observed between bodyweight and the number of biallelically expressed imprinted genes in LOS fetuses. Further, not only was there loss of allele-specific expression of imprinted genes in LOS, but we also observed differential transcript amounts of these genes between control and overgrown fetuses. In summary, we characterized previously unidentified imprinted genes in bovine and identified misregulation of imprinting at multiple loci in LOS. We concluded that LOS is a multi-locus loss-of-imprinting syndrome, as is BWS.
2015-03-06 | GSE63509 | GEO