Liver transcriptome analysis after DF-006 treatment in an HBV mouse model
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA867713 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A new chemical entity, DF-006, has been shown to suppress HBV replication in an AAV-HBV mouse model. DF-006 activates NF-kB signaling. In order to elucidate the mechanism of action of DF-006, specifically the genes expression stimulated in the liver that mediated its anti-HBV efficacy, we perform deep sequencing of RNA samples taken from AAV-HBV mice 4 hours after 10 μg/kg DF-006 oral administration or vehicle control. AAV-HBV mouse models were established by injecting male C57B6/J mice with 1011 vg/mouse AAV-HBV (genotype D, serotype ayw, GenBank accession number: KX449554). Dosing with DF-006 resulted in a statistically significant increase of gene expression for 1,685 genes in the liver. We performed an over-representation analysis for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and found 53 pathways were significantly enriched. The top 10 pathways included those that involved viral infection (e.g., herpes, influenza, Epstein-Barr, hepatitis B, measles) and those that involved host innate responses (TNF, osteoclast differentiation, NF-κB, toll-like receptor, RIG-I -like receptor). qPCR analysis confirmed genes that are directly or indirectly induced through NF-kB pathway and are reported before to play a role in HBV suppression.
2022-08-11 | GSE210856 | GEO
Project description:A large part of liver cancer is caused by hepatitis B virus (HBV) infection. In recent years, more and more reports have proved that circular RNAs (circRNAs) has a regulatory effect on the development of cancers, but the role of circRNAs in HBV-positive liver cancer needs to be further studied. In this study, the abnormally expressed circRNAs in two HBV-positive liver cancer cells compared to another two HBV-negative liver cancer cell lines were identified through microarray analysis. This study provides a comprehensively circRNA expression profiling in HBV-positive liver cancer cells, which is meaning for the mechanism study of circRNAs in HBV-related liver cancer.
2021-12-05 | GSE181988 | GEO
Project description:We analyzed three clinical parameters with gene expression data from 122 liver tissues. Six healthy samples were used in validation. All hepatitis samples were HBV infected, which was validated by positive HBsAg or serum HBV-DNA. The samples with HCV infection or metabolic liver injury (e.g. fatty liver, chronic alcoholic hepatitis, etc.) were excluded. This dataset is part of the TransQST collection.
2017-02-28 | E-GEOD-83148 | biostudies-arrayexpress
Project description:31 non-tumor liver tissues from 31 HBV-related HCC patients
2015-11-13 | GSE74925 | GEO
Project description:Here we interrogate the potential of human liver organoids as a platform for modeling HBV infection and related tumorigenesis. We show that organoids derived from HBV-infected patients display an aberrant early cancer gene signature, which clusters with the HCC cohort on the TCGA LIHC dataset and away from healthy liver tissue.
2020-02-20 | GSE126798 | GEO
Project description:The presentation of virus-derived peptides by HLA class I molecules on the surface of an infected cell and the recognition of these HLA-peptide complexes by, and subsequent activation of, CD8+ cytotoxic T cells provides an important mechanism for immune protection against viruses. Recent advances in proteogenomics have allowed researchers to discover a growing number of unique HLA-restricted viral peptides, resulting in a rapidly expanding repertoire of targets for immunotherapeutics (i.e. bispecific antibodies, engineered T-cell receptors (TCRs), chimeric antigen receptor T-cells (CAR-Ts)) to infected tissues. However, genomic variability between viral strains, such as Hepatitis-B virus (HBV), in combination with differences in patient HLA alleles, make it difficult to develop therapeutics against these targets. To address this challenge, we developed a novel proteogenomics approach for generating patient-specific databases that enable the identification of viral peptides based on the viral transcriptomes sequenced from individual patient liver samples. We also utilized DNA sequencing of patient samples to identify HLA genotypes and assist in target selection. Liver samples from 48 HBV infected patients, primarily from Asia, were examined to reconstruct patient-specific HBV genomes, identify regions within the human chromosomes targeted by HBV integrations and obtain a comprehensive view of HBV peptide epitopes using our HLA class-I (HLA-I) immunopeptidomics discovery platform. Two previously reported HLA associated HBV-derived peptides, HLA-A02 binder FLLTRILTI (S194-202) from the large surface antigen and HLA-A11 binder STLPETTVVRR (C141-151) from the capsid protein were validated by our discovery platform, but both were detected at a very low frequencies. In addition, we identified and validated, using heavy peptide analogues, novel strain-specific HBV-HLA associated peptides, such as GSLPQEHIVQK (P606-616) and variants. Overall, our novel approach can guide the development of bispecific antibody, TCR-T, or CAR-T based therapeutics for the treatment of HBV-related HCC and inform vaccine development.
2023-01-03 | PXD037270 | Pride
Project description:Purpose:Next-generation sequencing (NGS) were performed to investigate the differentially expressed molecular signature that were associated with HBV-mediated liver fibrosis Method: four cDNA libraries of separated groups ranging from 1, 3, 6-months post injection were constructed in the HBV (-) and analyzed using RNA-seq. results: Sequencing of the clean reads resulted in ~29–40 million reads per sample, for a total of ~438 million reads across 12 samples. Specifically, an average of 16,782, 17,088, 18,701, and 19,364 genes were identified in the HBV (+) mouse (1, 3, 6-months post injection) and HBV (-) mouse (control groups), respectively.
2017-02-28 | GSE95424 | GEO
Project description:To investigate whether HBsAg intrauterine exposure affected the offspring's immune response against HBV and the relevant mechanism, the difference of fetal liver tissue transcriptome between the C57BL/6 mice and C57BL/6-Tg (HBV Alb-1) Bri44 HBV transgenic mice was analyzed.
2021-12-01 | GSE162717 | GEO
Project description:Purpose: Chronic Hepatitis B virus (HBV) infection leads to liver fibrosis which is a major risk factor in Hepatocellular carcinoma (HCC) and an independent risk factor of recurrence after HCC tumor resection. HBV genome can be inserted into human genome, and chronic inflammation may trigger somatic mutations. Several studies characterized HBV integration sites in HCC patients with regard to frequently occurring hotspots. However, how HBV integration and other genomic changes contribute to the risk of tumor recurrence with regard to different degree of liver fibrosis is not clearly understood. In this study, we aim to find potential molecular mechanisms underlying tumor recurrence of HBV-associated HCC (HBV-HCC) with different degree of liver fibrosis. Methods: We performed RNA sequencing of 21 pairs of tumor and non-neoplastic liver tissues of HBV-HCC patients and performed comprehensive genomic analysis of our RNAseq data and public available sequencing data related to HBV-HCC. We developed a robust pipeline for sensitively identifying HBV integration sites based on sequencing data. Simulations with sequencing data showed that our method outperformed existing methods. We also compared SNPs of each sample with SNPs in cancer census database and inferred patient’s pathogenic SNP loads in tumor and non-neoplastic liver tissues. Conclusions: The HBV-integration and pathogenic SNP load patterns for HCC recurrence risk vary depending on liver fibrosis stage, suggesting potentially different tumorigenesis mechanisms for low and high liver fibrosis patients.
2018-03-01 | GSE94660 | GEO