Homo sapiens
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ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-54747
PROVIDER: PRJNA237545 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:An intrahepatic gene expression signature of enhanced immune activity predicts response to peginterferon and adefovir in chronic hepatitis B patients
2020-04-16 | E-GEOD-54747 | ExpressionAtlas
Project description:The natural history of chronic hepatitis B virus (HBV) infection could be divided in different phases by transaminase and HBV replication levels. However, it remains unknown how the intrahepatic transcriptomes in patients are correlated with the clinical phases. Here, we determined the intrahepatic transcriptomes of chronic hepatitis B patients and examined the role of specific groups of genes, including immune-related genes, in the control of hepatitis B virus infection.
2016-03-31 | GSE65359 | GEO
Project description:The natural history of chronic hepatitis B virus (HBV) infection could be divided in different phases by transaminase and HBV replication levels. However, it remains unknown how the intrahepatic transcriptomes in patients are correlated with the clinical phases. Here, we determined the intrahepatic transcriptomes of chronic hepatitis B patients and examined the role of specific groups of genes, including immune-related genes, in the control of hepatitis B virus infection. The transcriptomes of 83 chronic hepatitis B patients (22 immune tolerant, 50 immune clearance, and 11 inactive carrier state) were analyzed by performing microarray analysis of liver biopsies.KEGG pathway analysis showed that immune response genes and interferon-stimulated genes were up-regulated in the immune clearance phase. Although immune tolerant patients and inactive state carriers had significantly different serum viral loads, the hepatic transcriptomes of the two groups were largely similar and only significantly differed in the expression of 109 genes (p < 0.01). Thus, we hypothesized that some of the 109 genes may be involved in HBV control and identified genes of interest by performing systematic screening using specific siRNAs. We showed that silencing candidate genes such as EVA1A resulted in significantly increased viral replication. Conversely, overexpression of candidate genes suppressed virus replication. Conclusions: The immune related pathways were up-regulated in the immune clearance phase but not in the inactive carrier phase. A number of host genes unrelated to immune pathways were expressed in the inactive carrier phase and these may participate in the control of hepatitis B virus replication, resulting in low viral replication. This dataset is part of the TransQST collection.
2016-03-31 | E-GEOD-65359 | biostudies-arrayexpress
Project description:In this study we aimed to identify a baseline intrahepatic transcriptional signature associated with response in chronic hepatitis B patients treated with peginterferon-alfa-2a (peg-IFN) and adefovir. Liver gene expression values of patients with combined response (responders; n=9) and non-response (n=6) were compared for 21,462 annotated gene transcripts. We identified 182 genes which differed on average more than 1.5-fold, of which 53 were relatively upregulated in non-responders and 129 in responders. 15 liver biopsies of chronic hepatitis B patients were selected for RNA extraction and hybridization on Affymetrix microarrays. Expression values in 9 biopsies of patients with a combined response to therapy were compared with 6 biopsies of non-responders. Differentially expressed genes between responders and non-responders were determined using filtering on minimal average expression, fold change (1.5 fold) and p-values from 2-sided t-tests (0 permutations) in GenePattern. This dataset is part of the TransQST collection.
2014-12-19 | E-GEOD-54747 | biostudies-arrayexpress
Project description:In this study we aimed to identify a baseline intrahepatic transcriptional signature associated with response in chronic hepatitis B patients treated with peginterferon-alfa-2a (peg-IFN) and adefovir. Liver gene expression values of patients with combined response (responders; n=9) and non-response (n=6) were compared for 21,462 annotated gene transcripts. We identified 182 genes which differed on average more than 1.5-fold, of which 53 were relatively upregulated in non-responders and 129 in responders.
2014-12-19 | GSE54747 | GEO
Project description:The Eastern woodchuck (Marmota monax) is naturally infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to the human hepatitis B virus (HBV). The woodchuck is used as an animal model for studying chronic hepatitis B (CHB) and HBV-associated hepatocellular carcinoma (HCC) in humans, but the lack of sequence information has hitherto precluded functional genomics analysis. To address this major limitation of the model, we report here the sequencing, assembly and annotation of the woodchuck transcriptome, together with the generation of custom woodchuck microarrays. Using this new platform, we characterized the transcriptional response to persistent WHV infection and WHV-induced HCC. This revealed that chronic WHV infection, like HBV, is associated with (i) a limited intrahepatic type I interferon response, (ii) intrahepatic induction of markers associated with T cell exhaustion, (iii) elevated levels of suppressor of cytokine signaling 3 (SOCS3) in the liver, and (iv) intrahepatic accumulation of neutrophils. Underscoring the translational value of the woodchuck model, this study also determined that WHV-induced HCC shares molecular characteristics with a subtype of human HCC with poor prognosis. Conclusion: Our data establish the translational value of the woodchuck model and provide new insights into immune pathways which may play a role either in the persistence of HBV infection or the sequelae of CHB. Custom microarrays, generated from sequences obtained in transcriptome sequencing of woodchuck liver and PBMCs, were used to examine non-tumor vs. tumor gene expression in liver samples obtained from animals chronically infected with WHV (n=13). Multiple technical replicates per woodchuck sample are included.
2012-04-10 | E-GEOD-36545 | biostudies-arrayexpress
Project description:The woodchuck model of hepatitis B virus (HBV) infection displays many characteristics of human infection and has particular value for characterizing the host immune responses during the development of chronic infection. Using the newly developed custom woodchuck microarray platform, we compared the intrahepatic transcriptional responses of neonatal woodchucks with self-limiting and progressing persistent infection with woodchuck hepatitis virus (WHV). This revealed that WHV does not induce intrahepatic gene expression during the early acute stage of infection (8 weeks), suggesting it is a M-bM-^@M-^\stealthM-bM-^@M-^] virus. At the mid-acute phase of infection (14 weeks), resolution was associated with induction of a prominent cytotoxic T cell signature, with perforin and other markers of immune-mediated cytotolytic response being strongly expressed. Strikingly, this was accompanied by high level expression of PD-1 and various other inhibitory T cell receptors, which likely act to minimize liver damage by cytotoxic T cells during viral clearance. Conversely, self-limiting infection was not associated with a strong interferon-M-NM-1/M-NM-2 (IFN-M-NM-1/M-NM-2) transcriptional response, while the IFN-M-NM-3 signaling response (as measured by expression of CXCL9) in the mid-acute phase was comparable to that in chronically infected adult animals. Nevertheless, viperin and other antiviral genes were differentially expressed during resolving infection, suggesting that a subset of interferon-stimulated genes (ISGs) may play a role in the control of WHV replication. Conclusion: This study identifies new immune pathways associated with the clearance of hepadnavirus infection and reveals novel targets with potential for the treatment of chronic hepatitis B. Neonatal woodchucks of both genders were infected at 3 days of age with the same WHV7P1 inoculum containing 5 x 106 WID50 of WHV strain WHV7-11. Custom microarrays were generated from sequences obtained in transcriptome sequencing of woodchuck liver and PBMCs, and were used to examine liver gene expression in animals which eventually become chronically infected with WHV (8 weeks, n=5; 14 weeks, n=9), animals that eventually resolve WHV infection (8 weeks, n=10;14 weeks, n=7) and uninfected animals (8 weeks, n=5;14 weeks,n=5).
2012-09-22 | E-GEOD-37683 | biostudies-arrayexpress
Project description:The woodchuck model of hepatitis B virus (HBV) infection displays many characteristics of human infection and has particular value for characterizing the host immune responses during the development of chronic infection. Using the newly developed custom woodchuck microarray platform, we compared the intrahepatic transcriptional responses of neonatal woodchucks with self-limiting and progressing persistent infection with woodchuck hepatitis virus (WHV). This revealed that WHV does not induce intrahepatic gene expression during the early acute stage of infection (8 weeks), suggesting it is a “stealth” virus. At the mid-acute phase of infection (14 weeks), resolution was associated with induction of a prominent cytotoxic T cell signature, with perforin and other markers of immune-mediated cytotolytic response being strongly expressed. Strikingly, this was accompanied by high level expression of PD-1 and various other inhibitory T cell receptors, which likely act to minimize liver damage by cytotoxic T cells during viral clearance. Conversely, self-limiting infection was not associated with a strong interferon-α/β (IFN-α/β) transcriptional response, while the IFN-γ signaling response (as measured by expression of CXCL9) in the mid-acute phase was comparable to that in chronically infected adult animals. Nevertheless, viperin and other antiviral genes were differentially expressed during resolving infection, suggesting that a subset of interferon-stimulated genes (ISGs) may play a role in the control of WHV replication. Conclusion: This study identifies new immune pathways associated with the clearance of hepadnavirus infection and reveals novel targets with potential for the treatment of chronic hepatitis B.
2012-09-22 | GSE37683 | GEO
Project description:With 350 million carriers worldwide who may suffer from serious sequelae, including hepatocellular carcinoma, chronic hepatitis B virus (CHB) infection remains an important health issue. Current antiviral therapies hardly eradicate the virus. Therefore, there are still imperative need to develop new therapeutic strategies and predictors for treatment response to cure the disease and avoid futile treatment. By taking the advantage of having the paired liver biopsy samples of IFNalpha responders before/after treatment and pretreatment samples from responders and non-responders, we could characterize the intrahepatic expression profiles associated with necroinflammatory activity and the profiles/signature potentially predictive of response to IFNalpha therapy for CHB in this study.
2017-02-09 | GSE66699 | GEO
Project description:With 350 million carriers worldwide who may suffer from serious sequelae, including hepatocellular carcinoma, chronic hepatitis B virus (CHB) infection remains an important health issue. Current antiviral therapies hardly eradicate the virus. Therefore, there are still imperative need to develop new therapeutic strategies and predictors for treatment response to cure the disease and avoid futile treatment. By taking the advantage of having the paired liver biopsy samples of IFNalpha responders before/after treatment and pretreatment samples from responders and non-responders, we could characterize the intrahepatic expression profiles associated with necroinflammatory activity and the profiles/signature potentially predictive of response to IFNalpha therapy for CHB in this study.
2017-02-09 | GSE66698 | GEO