Transcriptome analysis of liver tissue in HBV - associated liver fibrosis mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE95424 | GEO | 2017/02/28
SECONDARY ACCESSION(S): PRJNA377098
REPOSITORIES: GEO
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Project description:: Hepatitis B virus (HBV) remains a major public health threat with more than 296 million people chronically infected worldwide at high risk to develop hepatocellular carcinoma. Current therapies are effective in suppressing HBV replication but rarely lead to cure. The fundamental limitation rests on the fact that current therapies do not affect the HBV covalently closed circular DNA (cccDNA), which serves as the template for viral transcription and replication and is highly stable in infected cells to ensure viral persistence. In this study, we aim to identify and elucidate the functional role of cccDNA-associated host factors using affinity purification and protein mass spectrometry in HBV-infected cells. HBV core protein (HBc) is associated with cccDNA. We used an anti-HBc antibody to pull down HBcAg-associated cccDNA complex in nuclear extract of HBV-infected HepG2-NTCP cells. By protein mass spectrometry, we identified many host proteins, including previously known proteins, that are associated with HBV cccDNA. Some of these proteins were functionally validated to play a role in HBV cccDNA activities.
2024-06-16 | PXD042733 | Pride
Project description:Purpose: Aberrantly methylated DNA are hallmarks for many cancers, HCC included. Tumor shed its DNA into circulation stream, and serum DNA methylation analysis is a less-invasive and accessable way to judge the primary tumor status. The goals of this study are to compare DNA methylation profiling in serum cell-free DNA from different stages of HCC progression including healthy control, chronic HBV carrier, HBV-related liver Cirrhosis and HCC, to establish HCC development-related aberrnat DNA methylation patterns. Methods: MBD methylCap/seq was carried out to screen differentially methylated CpG islands in serum cell-free DNA on four different stage of HBV-related HCC development. MSP and multiplex-BSP validation was performed using independent serum DNA or tumor and adjacent tissues. Results: Using a MBD methylCap/seq platform, we produced 33- to 37- million raw reads per sample and mapped them, in about half of the raw reads, to human genome(build h19) in the serum cf DNA of healthy control, HBV carrier, HBV cirrhosis and HCC. The mapped reads formed 180k to 260k peaks per sample, with 160 k common peaks shared by four samples. After subtraction of the common peaks, there left 51k, 107k and 78 k DMRs representing hypermethylations, in HBV carrier, HBV cirrhosis and HCC, respectively. We define those DMRs as early, middle and late when these DMRS occurred and maintained in HBV carrier, HBV cirrhosis and HCC, which including 27k, 24k and 19k DMRs, corresponding to 1,416, 1,337, 1,006 genes. GO analysis of them revealed gene categories and pathways associated with tumorogenenisis related process Conclusions: Our study represents the first detailed analysis of serum cf-DNA methylation profiling in the progression of HBV related HCC development. The processed data analysis here offers a comprehensive evaluation of DNA methylation in serum cf DNA. We conclude that MBD methylCap/seq based methylation profiling would benefit epigenetic research in HCC.
2015-02-11 | GSE54961 | 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:Cell: HBV-infected PHH cells. Methods: PHH cells were infected with 2000 genome equivalents/cell of HBV particles in the presence of 4% PEG8000. Seven days after HBV infection, ChIP-Seq analysis of cccDNA in HBV-infected PHHs was carried out. HBV-infected PHH cells were digested with micrococcal nuclease and resulting mononucleosomes purified by sucrose gradient centrifugation. Nucleosomes were enriched with anti-H3K79succ antibodies by ChIP assay and the associated DNA contained both human and HBV DNA fragments was analyzed by deep sequencing. The HBV-specific reads in ChIP-Seq pilot experiments was quantified and normalized by the reads mapped to the human genome.
2021-11-14 | GSE188634 | 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:This study aimed to better characterize the repertoire of serum HBV RNAs during chronic HBV infection in humans, which remains understudied. Using RT-PCR, qPCR, RNA-sequencing and immuno-precipitation, we found that (i) >50% of serum samples bore different amounts of HBV replication-derived RNAs (rd-RNAs); (ii) a few samples contained RNAs transcribed from integrated HBV DNA including 5'-HBV-human-3' RNAs (integrant-derived RNAs or id-RNAs) and 5'-human-HBV-3' transcripts as a minority of serum HBV RNAs; (iii) spliced HBV RNAs were abundant in <50% of analyzed samples; (iv) most serum rd-RNAs were polyadenylated via conventional HBV polyadenylation signal; (v) pre-genomic RNA (pgRNA) was the major component of the pool of serum RNAs; (vi) area of HBV positions 1531-1739 had very high RNA reads coverage and thus should be used as a target for detecting serum HBV RNAs; (vii) vast majority of rd-RNAs and pgRNA were associated with HBV virions, but not with unenveloped capsids, exosomes, classic microvesicles or apoptotic vesicles and bodies; (viii) considerable rd-RNAs presence in the circulating immune complexes was found in a few samples; and (ix) serum rcDNA and rd-RNAs should be quantified simultaneously to evaluate HBV replication status and efficacy of anti-HBV therapy with nucleos(t)ide analogs. In summary, sera contain various HBV RNA types of different origin, which are likely secreted via different mechanisms. In addition, since we previously showed that id-RNAs were abundant or predominant HBV RNAs in many of liver and hepatocellular carcinoma tissues comparing to rd-RNAs, there is likely a mechanism favoring the egress of the replication-derived RNAs.
2023-02-26 | GSE224901 | 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:RNA-seq is a powerful tool for comprehensive characterization of whole transcriptome at both gene and exon levels and with a unique ability of identifying novel splicing variants. To date, RNA-seq analysis of HBV-related HCC has not been reported. In this study, we performed transcriptome analyses for 10 matched pairs of cancer and non-cancerous tissues from Chinese HBV-related hepatocelluar carcinoma patients using 36bp single-end sequencing approach on Solexa/Illumina GAII platform. On average, about 21.6 million sequencing reads and 10.6 million aligned reads were obtained for samples sequenced on each lane, which was able to identify > 50% of all the annotated genes for each sample. Furthermore, from by far the largest database of transcripts expressed in HCC tissues, we identified 1,378 significantly differently expressed genes (DEGs) and 24, 338 differentially expressed exons (DEEs). Comprehensive function analyses indicated that cell growth-related, metabolism-related and immune-related pathways were most significantly enriched by DEGs, pointing to a complex mechanism for HCC carcinogenesis. Positional gene enrichment analysis showed that DEGs were most significantly enriched at chromosome 8q21.3-24.3. The most interesting findings were from the analysis at exon levels where we characterized three major patterns of expression changes between gene levels and exon levels, implying a much complex landscape of transcript-specific differential expressions in HCC. Finally, we identified a novel highly up-regulated exon-exon junction in ATAD2 (ATPase family, AAA domain containing 2) gene in HCC tissues. Overall, to our best knowledge, our study represents the most comprehensive characterization of the HBV-related HCC transcriptome including exon level expression changes and novel splicing variants, which illustrated the power of RNA-seq and provided important clues for understanding the molecular mechanisms of HCC pathogenesis at system-wide levels. A comprehensive analysis of transcriptome for 10 match-paired HBV-related Chinese HCC and non-cancerous adjacent tissues. Processed data files: Exon-level results, gene-level results, differentially expressed exons, and differently expressed genes (DEGs).
2013-11-24 | E-GEOD-25599 | biostudies-arrayexpress
Project description:31 non-tumor liver tissues from 31 HBV-related HCC patients
2015-11-13 | GSE74925 | GEO
Project description:Purpose: Chronic infection with hepatitis B virus is the leading global risk factor for the development of liver cancer. A large body of research has shown the many effects an HBV infection has on cellular physiology, particularly on pathways that may be involved in the development of HBV-associated diseases. Unfortunately, a significant portion of this research has been done in systems that may not mimic what is seen in a primary hepatocyte, and is not done on a transcriptome-wide scale. Because of this, we performed an RNA-seq analysis of primary rat hepatocytes expressing HBV to determine the global changes HBV has on primary hepatocyte physiology. Methods: To do this RNA-seq analysis, triplicate samples of total RNA were collected from cultured primary rat hepatocytes infected with adenovirus expressing GFP alone (AdGFP) or GFP along with a greater than unit length copy of the HBV genome (AdHBV). Samples were collected either 24h or 48h after infection. cDNA libraries were sequenced two times using the Illumina HiSeq or Illumina NextSeq platform to generate either 1x50bp or 1x75bp reads. Reads from each sequencing run were mapped using the STAR aligner, and output BAMs were merged into a single BAM for each sample. The merged BAM was further analyzed in R using the GenomicAlignments package to quantify number of reads per transcript and DESeq2 to determine differential expression. Reads per kilobase transcript per million total reads (RPKM) was calculated by dividing reads per transcript by the transcript length and then normalizing to the total number of reads in the sample. Results: Following this pipeline, we were able to identify a number of HBV-mediated differentially expressed transcripts at 24h and 48h post-infection. Further pathway analysis of these differentially expressed transcripts identified many important cellular pathways, including those involved with cell cycle regulation and metabolism, as being differentially regulated by HBV in primary hepatocytes. mRNA profiles of HBV-expressing and non-expressing primary rat hepatocytes were generated, in triplicate, 24h and 48h post-infection using Illumina HiSeq 2500 and NextSeq 500 instruments.
2016-01-15 | E-GEOD-66566 | biostudies-arrayexpress