scholarly journals Transcriptome analysis of sevoflurane exposure effects at the different brain regions

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0236771
Author(s):  
Hiroto Yamamoto ◽  
Yutaro Uchida ◽  
Tomoki Chiba ◽  
Ryota Kurimoto ◽  
Takahide Matsushima ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Brain Regions ◽  
Rna Seq ◽  
Ontology Term ◽  
Binding Motifs ◽  
Term Enrichment Analysis ◽  
Term Enrichment ◽  
Differently Expressed Genes

Backgrounds Sevoflurane is a most frequently used volatile anesthetics, but its molecular mechanisms of action remain unclear. We hypothesized that specific genes play regulatory roles in brain exposed to sevoflurane. Thus, we aimed to evaluate the effects of sevoflurane inhalation and identify potential regulatory genes by RNA-seq analysis. Methods Eight-week old mice were exposed to sevoflurane. RNA from medial prefrontal cortex, striatum, hypothalamus, and hippocampus were analysed using RNA-seq. Differently expressed genes were extracted and their gene ontology terms were analysed using Metascape. These our anesthetized mouse data and the transcriptome array data of the cerebral cortex of sleeping mice were compared. Finally, the activities of transcription factors were evaluated using a weighted parametric gene set analysis (wPGSA). JASPAR was used to confirm the existence of binding motifs in the upstream sequences of the differently expressed genes. Results The gene ontology term enrichment analysis result suggests that sevoflurane inhalation upregulated angiogenesis and downregulated neural differentiation in each region of brain. The comparison with the brains of sleeping mice showed that the gene expression changes were specific to anesthetized mice. Focusing on individual genes, sevoflurane induced Klf4 upregulation in all sampled parts of brain. wPGSA supported the function of KLF4 as a transcription factor, and KLF4-binding motifs were present in many regulatory regions of the differentially expressed genes. Conclusions Klf4 was upregulated by sevoflurane inhalation in the mouse brain. The roles of KLF4 might be key to elucidating the mechanisms of sevoflurane induced functional modification in the brain.

scholarly journals Transcriptome analysis of sevoflurane exposure effects at the different brain regions

2020 ◽  
Author(s):  
Hiroto Yamamoto ◽  
Yutaro Uchida ◽  
Tomoki Chiba ◽  
Ryota Kurimoto ◽  
Takahide Matsushima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Ontology ◽  
Neural Development ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Transcriptional Analysis ◽  
Rna Seq ◽  
Ontology Term ◽  
Whole Brain ◽  
Differently Expressed Genes

AbstractBackgroundsSevoflurane is a most frequently used volatile anaesthetics, but its molecular mechanisms of action remain unclear. We hypothesized that specific genes play regulatory roles in whole brain exposed to sevoflurane. Thus, we aimed to evaluate the effects of sevoflurane inhalation and identify potential regulatory genes by RNA-seq analysis.MethodsEight-week old mice were exposed to sevoflurane. RNA from four medial prefrontal cortex, striatum, hypothalamus, and hippocampus were analysed using RNA-seq. Differently expressed genes were extracted. Their gene ontology terms and the transcriptome array data of the cerebral cortex of sleeping mice were analysed using Metascape, and the gene expression patterns were compared. Finally, the activities of transcription factors were evaluated using a weighted parametric gene set analysis (wPGSA). JASPAR was used to confirm the existence of binding motifs in the upstream sequences of the differently expressed genes.ResultsThe gene ontology term enrichment analysis result suggests that sevoflurane inhalation upregulated angiogenesis and downregulated neural differentiation in the whole brain. The comparison with the brains of sleeping mice showed that the gene expression changes were specific to anaesthetized mice. Sevoflurane induced Klf4 upregulation in the whole brain. The transcriptional analysis result suggests that KLF4 is a potential transcriptional regulator of angiogenesis and neural development.ConclusionsKlf4 was upregulated by sevoflurane inhalation in whole brain. KLF4 might promote angiogenesis and cause the appearance of undifferentiated neural cells by transcriptional regulation. The roles of KLF4 might be key to elucidating the mechanisms of sevoflurane induced functional modification in the brain.

DiNGO: standalone application for Gene Ontology and Human Phenotype Ontology term enrichment analysis

2019 ◽  
Author(s):  
Radoslav Davidović ◽  
Vladimir Perovic ◽  
Branislava Gemovic ◽  
Nevena Veljkovic
Keyword(s):  
Gene Ontology ◽  
Source Code ◽  
Enrichment Analysis ◽  
Human Phenotype Ontology ◽  
Supplementary Information ◽  
Phenotype Ontology ◽  
Ontology Term ◽  
Human Phenotype ◽  
Term Enrichment Analysis ◽  
Term Enrichment

Abstract Summary Although various tools for Gene Ontology (GO) term enrichment analysis are available, there is still room for improvement. Hence, we present DiNGO, a standalone application based on an open source code from BiNGO, a widely-used application to assess the overrepresentation of GO categories. Besides facilitating GO term enrichment analyses, DiNGO has been developed to allow for convenient Human Phenotype Ontology (HPO) term overrepresentation investigation. This is an important contribution considering the increasing interest in HPO in scientific research and its potential in clinical settings. DiNGO supports gene/protein identifier conversion and an automatic updating of GO and HPO annotation resources. Finally, DiNGO can rapidly process a large amount of data due to its multithread design. Availability and Implementation DiNGO is implemented in the JAVA language, and its source code, example datasets and instructions are available on GitHub: https://github.com/radoslav180/DiNGO. A pre-compiled jar file is available at: https://www.vin.bg.ac.rs/180/tools/DiNGO.php Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals TFTenricher: a python toolbox for annotation enrichment analysis of transcription factor target genes

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Rasmus Magnusson ◽  
Zelmina Lubovac-Pilav
Keyword(s):  
Gene Ontology ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Ontology Term ◽  
Term Enrichment ◽  
Transcription Factor Target ◽  
Downstream Processes ◽  
Biological Context

Abstract Background Transcription factors (TFs) are the upstream regulators that orchestrate gene expression, and therefore a centrepiece in bioinformatics studies. While a core strategy to understand the biological context of genes and proteins includes annotation enrichment analysis, such as Gene Ontology term enrichment, these methods are not well suited for analysing groups of TFs. This is particularly true since such methods do not aim to include downstream processes, and given a set of TFs, the expected top ontologies would revolve around transcription processes. Results We present the TFTenricher, a Python toolbox that focuses specifically at identifying gene ontology terms, cellular pathways, and diseases that are over-represented among genes downstream of user-defined sets of human TFs. We evaluated the inference of downstream gene targets with respect to false positive annotations, and found an inference based on co-expression to best predict downstream processes. Based on these downstream genes, the TFTenricher uses some of the most common databases for gene functionalities, including GO, KEGG and Reactome, to calculate functional enrichments. By applying the TFTenricher to differential expression of TFs in 21 diseases, we found significant terms associated with disease mechanism, while the gene set enrichment analysis on the same dataset predominantly identified processes related to transcription. Conclusions and availability The TFTenricher package enables users to search for biological context in any set of TFs and their downstream genes. The TFTenricher is available as a Python 3 toolbox at https://github.com/rasma774/Tftenricher, under a GNU GPL license and with minimal dependencies.

Analysis of Expression Profiles of mRNA and lncRNA in Oviduct During Estrus Phase of Sheep (Ovis Aries) with Two Fecundity (FecB Gene) Genotypes

2021 ◽  
Author(s):  
Weihao Chen ◽  
Zhifeng Li ◽  
Wei Sun ◽  
Mingxing Chu
Keyword(s):  
Embryo Development ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Ovis Aries ◽  
Functional Enrichment ◽  
Saga Complex ◽  
Rna Seq ◽  
Estrus Phase

Abstract Background:In sheep, FecB is the essential biomarker of the fertility, previous researches have provided a detailed insight on the regulation involved estrus phase and FecB in the reproductive-related tissues including hypothalamus, pituitary, and ovary. However, as the host of embryo development and connection between the ovary and the uterus, little is known about the interaction between mRNAs and lncRNAs in sheep oviduct. In the present study, RNA-Seq was performed to identify the transcriptomic profiles of mRNAs and lncRNAs in oviduct during estrus phase of sheep with FecBBB/++ genotypes.Results:In total, 21,863 lncRNAs and 43,674 mRNAs were identified, 57 DE lncRNAs and 637 DE mRNAs were revealed in the comparisons between follicular phase and luteal phase, 26 DE lncRNAs and 421 DE lncRNAs were revealed in the comparisons between FecB BB genotype and FecB ++ genotype. Functional enrichment analysis suggested that GO and KEGG terms related to reproduction such as SAGA complex, ATP-binding cassette (ABC), Nestin, and Hippo signalling pathway. DE-interaction network suggested that LNC_018420 maybe the key regulators related to embryo development in sheep oviduct.Conclusion:This was the first study to reveal the transcriptomic profiles of mRNAs and lncRNAs in the oviduct of FecB BB/++ sheep at estrus phase using RNA-Seq. Our findings can provide new understanding on the molecular mechanisms of mRNAs and lncRNAs underlying sheep embryo development and also opening new lines of investigation in sheep reproduction.

scholarly journals Transcriptome Analysis of Testes and Uterus: Reproductive Dysfunction Induced by Toxoplasma gondii in Mice

2020 ◽  
Vol 8 (8) ◽  
pp. 1136
Author(s):  
Junjie Wang ◽  
Tanghui Liu ◽  
Yasser S. Mahmmod ◽  
Zipeng Yang ◽  
Jiexing Tan ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Toxoplasma Gondii ◽  
Acute Infection ◽  
The Other ◽  
Rna Seq ◽  
Mice Model ◽  
Reproductive Disorders ◽  
Kegg Database ◽  
Disease Pathogenesis ◽  
Differently Expressed Genes

Toxoplasma gondii (T. gondii) infection in female mammals during pregnancy can result in poor pregnancy. Similarly, it can result in male reproductive disorders in male mammals. Although the testes and uterus have very different biological makeup, they are still both attacked by T. gondii resulting in reproductive dysfunctions. We hypothesized that there are significant common genes in the testes and uterus that interact with T. gondii. Finding out and studying these genes is vital to understand the infection mechanism of T. gondii and the induced disease pathogenesis. To achieve this goal, we built a mice model of acute infection with T. gondii and the testes and uterus of the mice were sequenced by RNA-Seq. A total of 291 and 679 significantly differently expressed genes (DEGs) were obtained from the testes and the uterus, respectively. In the Gene Ontology (GO) analysis, part of the DEGs in the testes and uterus were related to 35 GO functions. When compared with the KEGG database, seven pathways affecting both the testes and uterus during the course of T. gondii infection were identified. In addition, Toxoplasmosis can significantly affect the expression of Nlrp5 and Insc leading to negative outcomes in the host. On the other hand, the host regulates Gbp7, Gbp2b, and Ifit3 to defend against T. gondii infection.

P5398CircRNAs deregulation in heart failure patients

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Greco ◽  
A Made' ◽  
M Longo ◽  
R Tikhomirov ◽  
S Castelvecchio ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Functional Characterization ◽  
Enrichment Analysis ◽  
Host Gene ◽  
Circular Rnas ◽  
Amplification Efficiency ◽  
Rna Seq ◽  
Bioinformatics Pipeline

Abstract Background Circular RNAs (circRNAs) are an emerging class of noncoding RNAs stemming from the splicing and circularization of pre-mRNAs exons. CircRNAs can regulate transcription and splicing, sequester microRNAs acting as “sponge” and inducing the respective targets, and bind to RNA binding proteins. Recently, they have been found deregulated in dilated cardiomyopathies (DCM), one of the cardiovascular diseases with the worst rate of morbidity and mortality, and whose molecular mechanisms are only partially known. Purpose Therein, we will evaluate in ischemic DCM patients the modulation of 17 circRNAs, 14 out of them obtained from literature data on DCM ischemic or not, while the other 3 were circRNAs not characterized in the heart previously. The study aims to identify circRNAs candidates for further functional characterization in DCM. In addition, as differential expression (DE) analysis is not easily performed for circRNAs in RNA-seq datasets, the validated circRNAs will be used to set up the most specific and sensitive bioinformatics pipeline for circRNA-DE analysis. Methods We designed divergent and convergent specific primers for 17 circRNAs and their host gene, respectively, and their amplification efficiency was measured by RT-qPCR. Transcripts expression was measured in left ventricle biopsies of 12 patients affected by non end-stage ischemic HF and of 12 matched controls. Results We identified cPVT1, cANKRD17, cBPTF as DE, and validated the modulation of 5 out of the 14 DCM-related circRNAs (cHIPK3, cALPK2, cPCMTD1, cNEBL, cSLC8A1), while cPDRM5, cTTN1 showed opposite modulation, which may be due to the specific disease condition. All of them were modulated differently from the respective host gene. CircRNA/miRNA interactions were predicted using Starbase 3.0. Next, mRNAs-targets of the identified miRNAs were predicted by mirDIP 4.1 and intersected with gene expression datasets of the same patients, previously obtained by microarray analysis. We found that cBPTF and cANKRD17 might sponge 12 and 2 miRNAs, respectively. Enrichment analysis of the relevant targets identified several important pathways implicated in DCM, such as MAPK, FoxO, EGFR, VEGF and Insulin/IGF pathways. In addition, deep RNA-Seq analysis that is currently ongoing and the validated circRNAs will be used to optimize the bioinformatics pipeline for circRNA DE analysis. Conclusions We identified a subset of circRNAs deregulated in ischemic HF potentially implicated in HF pathogenesis.

scholarly journals Dietary Enteromorpha Polysaccharides Supplementation Improves Breast Muscle Yield and Is Associated With Modification of mRNA Transcriptome in Broiler Chickens

2021 ◽  
Vol 8 ◽  
Author(s):  
Yue Zhao ◽  
Balamuralikrishnan Balasubramanian ◽  
Yan Guo ◽  
Sheng-Jian Qiu ◽  
Rajesh Jha ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Broiler Chickens ◽  
Molecular Mechanisms ◽  
Carcass Traits ◽  
Enrichment Analysis ◽  
Dietary Supplementation ◽  
Breast Muscle ◽  
Rna Seq ◽  
Feeding Trial ◽  
Mrna Transcriptome

The present study evaluated the effects of dietary supplementation of Enteromorpha polysaccharides (EP) on carcass traits of broilers and potential molecular mechanisms associated with it. This study used RNA-Sequencing (RNA-Seq) to detect modification in mRNA transcriptome and the cognate biological pathways affecting the carcass traits. A total of 396 one-day-old male broilers (Arbor Acres) were randomly assigned to one of six dietary treatments containing EP at 0 (CON), 1000 (EP_1000), 2500 (EP_2500), 4000 (EP_4000), 5500 (EP_5500), and 7000 (EP_7000) mg/kg levels for a 35-d feeding trial with 6 replicates/treatment. At the end of the feeding trial, six birds (one bird from each replicate cage) were randomly selected from each treatment and slaughtered for carcass traits analysis. The results showed that the dietary supplementation of EP_7000 improved the breast muscle yield (p < 0.05). Subsequently, six breast muscle samples from CON and EP_7000 groups (three samples from each group) were randomly selected for RNA-Seq analysis. Based on the RNA-Seq results, a total of 154 differentially expressed genes (DEGs) were identified (p < 0.05). Among the DEGs, 112 genes were significantly upregulated, whereas 42 genes were significantly down-regulated by EP_7000 supplementation. Gene Ontology enrichment analysis showed that the DEGs were mainly enriched in immune-related signaling pathways, macromolecule biosynthetic, DNA-templated, RNA biosynthetic, and metabolic process (p < 0.05). Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the DEGs were enriched in signaling pathways related to viral infectious diseases and cell adhesion molecules (p < 0.05). In conclusion, dietary inclusion of EP_7000 improves the breast muscle yield, which may be involved in improving the immunity and the cell differentiation of broilers, thus promoting the muscle growth of broilers. These findings could help understand the molecular mechanisms that enhance breast muscle yield by dietary supplementation of EP in broilers.

scholarly journals Analysis of Transcriptome and miRNAome in the Muscle of Bamei Pigs at Different Developmental Stages

Animals ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1198 ◽  
Author(s):  
Guofang Wu ◽  
Lin Ma ◽  
Lei Wang ◽  
Jiping Zhou ◽  
Yuhong Ma ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Meat Quality ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Developmental Stages ◽  
Enrichment Analysis ◽  
Rna Seq ◽  
Developmental Processes ◽  
Citrate Cycle ◽  
Molecular Approaches

The growth of skeletal muscle involves complex developmental processes that play an important part in the determinization of pork quality. The investigation of skeletal muscle mRNA or miRNA profiles is especially important for finding molecular approaches to improve meat quality in pig breeding. Therefore, we studied the transcriptome (mRNA and miRNA) profiles of skeletal muscle with RNA-Seq in three developmental stages of pigs: 65-day embryonic (E65), postnatal 0 days (natal) and 10 months (adult). We found 10,035, 9050 and 4841 differentially expressed (DE) genes for natal vs. E65, adult vs. E65 and adult vs. natal, 55, 101 and 85 DE miRNA for natal vs. E65, adult vs. E65 and adult vs. natal, respectively. In addition, the target genes of DE miRNA that was in a negative correlation with the corresponding miRNA in the same comparison group were selected for enrichment analysis. Gene Ontology terms were mainly classified into developmental processes. Pathway analysis revealed enrichment in the Rap1 signaling pathway, citrate cycle and oxidative phosphorylation and carbon. Finally, RT-PCR was employed for validating the level of expression of 11 DE miRNA and 14 DEGs. The transcriptome profiles of skeletal muscle from the different developmental stages of the Bamei pigs were obtained. From these data, hundreds of DE miRNA and mRNA, and the miRNA–mRNA regulatory network can provide valuable insights into further understanding of key molecular mechanisms and improving the meat quality in pig breeding.

scholarly journals Insights into the Synthesis, Secretion and Curing of Barnacle Cyprid Adhesive via Transcriptomic and Proteomic Analyses of the Cement Gland

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 186
Author(s):  
Guoyong Yan ◽  
Jin Sun ◽  
Zishuai Wang ◽  
Pei-Yuan Qian ◽  
Lisheng He
Keyword(s):  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Lysyl Oxidase ◽  
Enrichment Analysis ◽  
Salivary Secretion ◽  
Cement Gland ◽  
Differentially Expressed ◽  
Model Organisms ◽  
Rna Seq ◽  
Secretion Pathway

Barnacles represent one of the model organisms used for antifouling research, however, knowledge regarding the molecular mechanisms underlying barnacle cyprid cementation is relatively scarce. Here, RNA-seq was used to obtain the transcriptomes of the cement glands where adhesive is generated and the remaining carcasses of Megabalanus volcano cyprids. Comparative transcriptomic analysis identified 9060 differentially expressed genes, with 4383 upregulated in the cement glands. Four cement proteins, named Mvcp113k, Mvcp130k, Mvcp52k and Mvlcp1-122k, were detected in the cement glands. The salivary secretion pathway was significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differentially expressed genes, implying that the secretion of cyprid adhesive might be analogous to that of saliva. Lysyl oxidase had a higher expression level in the cement glands and was speculated to function in the curing of cyprid adhesive. Furthermore, the KEGG enrichment analysis of the 352 proteins identified in the cement gland proteome partially confirmed the comparative transcriptomic results. These results present insights into the molecular mechanisms underlying the synthesis, secretion and curing of barnacle cyprid adhesive and provide potential molecular targets for the development of environmentally friendly antifouling compounds.

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