Project description:Chronic high-altitude hypoxia causes significant ovarian tissue damage. This study investigates the underlying mechanisms of ovarian injury in mice exposed to hypoxia, aiming to guide targeted therapy development. Mice were divided into either normal pressure (MP, n=15) or hypobaric hypoxia (PU, n=15) and samples from both groups were analyzed using whole-transcriptome sequencing data. Hub genes were identified through differential expression analysis and protein-protein interaction (PPI) network construction before their expression patterns were examined. Subsequently, functional enrichment was conducted. Key miRNAs, lncRNAs, circRNAs, and transcription factors (TFs) were ascertained. Finally, RT-qPCR and Western blotting (WB) were performed. Hmgcr, Ptgs2, and Mmp3 were identified as hub genes, all showing pronounced lower expression in PU samples. RT-qPCR analysis confirmed the downregulation of these genes, with WB analysis further demonstrating a significant reduction in their protein levels in PU samples. These hub genes were predominantly enriched in "oxidative phosphorylation" pathway. Furthermore, lncRNA-miRNA-mRNA, circRNA-miRNA-mRNA, and TF-mRNA regulatory networks were constructed. These networks highlighted key regulatory molecules, including the miRNA mmu-miR-144-3p, 2 lncRNAs (Miat and Neat1), 8 circRNAs (eg. novel_circ_041272-mu-miR-144-3p-Ptgs2), and 1 TF (Etv4). These results provide key insights for targeted ovarian injury therapies under low-pressure hypoxia.
Project description:Chronic high-altitude hypoxia causes significant ovarian tissue damage. This study investigates the underlying mechanisms of ovarian injury in mice exposed to hypoxia, aiming to guide targeted therapy development. Mice were divided into either normal pressure (MP, n=15) or hypobaric hypoxia (PU, n=15) and samples from both groups were analyzed using whole-transcriptome sequencing data. Hub genes were identified through differential expression analysis and protein-protein interaction (PPI) network construction before their expression patterns were examined. Subsequently, functional enrichment was conducted. Key miRNAs, lncRNAs, circRNAs, and transcription factors (TFs) were ascertained. Finally, RT-qPCR and Western blotting (WB) were performed. Hmgcr, Ptgs2, and Mmp3 were identified as hub genes, all showing pronounced lower expression in PU samples. RT-qPCR analysis confirmed the downregulation of these genes, with WB analysis further demonstrating a significant reduction in their protein levels in PU samples. These hub genes were predominantly enriched in "oxidative phosphorylation" pathway. Furthermore, lncRNA-miRNA-mRNA, circRNA-miRNA-mRNA, and TF-mRNA regulatory networks were constructed. These networks highlighted key regulatory molecules, including the miRNA mmu-miR-144-3p, 2 lncRNAs (Miat and Neat1), 8 circRNAs (eg. novel_circ_041272-mu-miR-144-3p-Ptgs2), and 1 TF (Etv4). These results provide key insights for targeted ovarian injury therapies under low-pressure hypoxia.
Project description:Chronic high-altitude hypoxia causes significant ovarian tissue damage. This study investigates the underlying mechanisms of ovarian injury in mice exposed to hypoxia, aiming to guide targeted therapy development. Mice were divided into either normal pressure (MP, n=15) or hypobaric hypoxia (PU, n=15) and samples from both groups were analyzed using whole-transcriptome sequencing data. Hub genes were identified through differential expression analysis and protein-protein interaction (PPI) network construction before their expression patterns were examined. Subsequently, functional enrichment was conducted. Key miRNAs, lncRNAs, circRNAs, and transcription factors (TFs) were ascertained. Finally, RT-qPCR and Western blotting (WB) were performed. Hmgcr, Ptgs2, and Mmp3 were identified as hub genes, all showing pronounced lower expression in PU samples. RT-qPCR analysis confirmed the downregulation of these genes, with WB analysis further demonstrating a significant reduction in their protein levels in PU samples. These hub genes were predominantly enriched in "oxidative phosphorylation" pathway. Furthermore, lncRNA-miRNA-mRNA, circRNA-miRNA-mRNA, and TF-mRNA regulatory networks were constructed. These networks highlighted key regulatory molecules, including the miRNA mmu-miR-144-3p, 2 lncRNAs (Miat and Neat1), 8 circRNAs (eg. novel_circ_041272-mu-miR-144-3p-Ptgs2), and 1 TF (Etv4). These results provide key insights for targeted ovarian injury therapies under low-pressure hypoxia.
Project description:Model destription:
The model describes the stochastic dynamics of two variables, protein and mRNA of a gene with constitutive expression.
Publication:
A New Efficient Approach to Fit Stochastic Models on the Basis of High-throughput Experimental Data Using a Model of IRF7 Gene Expression as Case Study
Authors
Luis U. Aguilera, Christoph Zimmer and Ursula Kummer.
2017-03-17 | MODEL1608100000 | BioModels
Project description:High-throughput sequencing analysis of Mycoplasma hyopneumoniae protein interaction networks
Project description:The experiment aims to identify regulatory miRNA networks influencing mRNA profiles in oral lichen planus (OLP). RNA and miRNA were extracted simultaniously using miRVana (Ambion, Life Technologies). Sample and array processing was carried out according to the manufacturer's guidelines. Affymetrix raw data was processed using AGCC Expression Console 1.1 (Affymetrix), employing RMA normalization. Linking miRNA and mRNA was performed with a correlation analysis, while a false discovery rate was used to exclude false-positive correlations between miRNAs and their predicted targets.
Project description:The experiment aims to identify regulatory miRNA networks influencing mRNA profiles in oral lichen planus (OLP). RNA and miRNA were extracted simultaniously using miRVana (Ambion, Life Technologies). Sample and array processing was carried out according to the manufacturer's guidelines. Affymetrix raw data was processed using AGCC Expression Console 1.1 (Affymetrix), employing RMA normalization. Linking miRNA and mRNA was performed with a correlation analysis, while a false discovery rate was used to exclude false-positive correlations between miRNAs and their predicted targets.
Project description:We used miRNA-sequencing to identify candidate plasma pharmacodynamic (PD) biomarkers of interferon beta-1a (IFNβ-1a) biologics and to explore miRNA-mRNA targeted protein relationships and networks to support identified miRNA candidates. Plasma samples from 36 healthy subjects from a placebo-controlled randomized single dose clinical study with IFNβ-1a and pegIFNβ-1a were used. Mature miRNAs were measured using an in-house miRNA-seq workflow at baseline, at 9 timepoints over 6 days in IFNβ-1a group (n=11[30µg]), and at 11 timepoints over 13 days in pegIFNβ-1a group (n=11[125µg]) and placebo-specific groups (n=6 each). A miRNA was only considered expressed if it had a read count ≥10 in more than 50% of the samples across all treatment groups. Linear mixed-effects models (lmer) regressing miRNA changes with treatment, time and their interaction were used to identify differentially expressed miRNAs, which were further prioritized based on magnitude of response and biological relevance using in silico predicted miRNA-protein targets and regulatory network analyses. Ten and 13 miRNAs were impacted by IFNβ-1a and pegIFNβ-1a, respectively (lmer FDR-corrected p- value <0.1), compared to placebo, of which miR.223.3p and miR.21.5p were prioritized as candidate PD biomarkers for both products. Systems level analysis of integrated proteomics data highlighted miRNA protein targets for both miR.223.3p and miR.21.5p that were linked to previously reported top proteomic response proteins and predicted regulatory networks including IFN beta. Using miRNA-sequencing and linking candidates to predicted target proteins and regulatory networks, results suggest miR.223.3p and miR.21.5p as potential novel PD biomarkers of IFNβ-1a biologics for further investigation.