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Immune response- and viral control-related pathways in the progression of chronic hepatitis B
Zhi-Qiang Zou1, Shuai Zhang2, Qing Lin2
1Yantai City Hospital for Infectious Diseases, Yantai 264001, China.
Insights
This study reveals key gene expression pathways in chronic hepatitis B (CHB) patients, identifying specific sub-networks linked to disease phases. These findings offer insights into host responses and potential therapeutic targets for CHB.
Area of Science:
- Hepatology and Virology
- Genomics and Bioinformatics
- Immunology
Background:
- Chronic hepatitis B (CHB) presents a complex clinical course with advanced liver disease risk.
- Host immune responses significantly influence CHB progression.
- Hepatic transcriptome dynamics across CHB clinical phases remain largely uncharacterized.
Purpose of the Study:
- To identify specific gene expression sub-networks in different CHB phases.
- To infer potential pathways for predicting clinical outcomes in CHB.
- To understand the correlation between hepatic transcriptomes and CHB clinical phases.
Main Methods:
- Constructed differential co-expression networks (DCNs) by comparing hepatic transcriptomes across CHB phases.
- Identified critical genes and iteratively selected sub-networks using a snowball sampling strategy.
- Utilized permutation tests for statistical significance and assigned functional pathways to sub-networks.
Main Results:
- Identified specific sub-networks and pathways altered in immune clearance and inactive carrier phases of CHB.
- Observed significant changes in TGF-beta receptor signaling (EMT pathway) during the immune clearance phase.
- Detected alterations in nuclear receptor transcription and adenylate cyclase activating pathways in the inactive carrier state.
Conclusions:
- Differential co-expression network analysis revealed immune- and viral control-related pathways in CHB.
- Identified host transcriptome characteristics associated with CHB infection phases.
- Findings provide a foundation for understanding host responses and developing potential CHB therapeutic targets.
Background:
Chronic hepatitis B (CHB) is a complicated and dynamic course, and is associated with advanced liver disease. Host immune response against viral infection plays a pivotal role in the progression of CHB. However, it is still uncharted that how the hepatic transcriptomes in patients with CHB are correlated with the clinical phases.
Objective:
This study aimed to identify the specific sub-networks across various phases of CHB and infer potential pathways for phenotypic outcome prediction.
Methods:
In this study, we performed the pairwise comparisons of the hepatic transcriptomes of CHB patients under different phases, and constructed the differential co-expression networks (DCNs). We firstly identified the critical genes from each DCN according to the adjacency matrix of the network. Then, the specific sub-networks were digged by iteratively affiliating genes that can increase the classification accuracy, using a snow-ball sampling strategy. Permutation test was implemented to determine the statistical significance of these sub-networks. Finally, each sub-network was given a most significant functional pathway.
Results:
We constructed 3 DCNs by pairwise comparing the hepatic transcriptomes among three CHB phases, and systemically tracked 1, 1 and 2 specific sub-networks and pathways, respectively. Relative to immune tolerant phase, TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) pathway was significantly changed in the immune clearance phase, and nuclear receptor transcription pathway and adenylate cyclase activating pathway were altered in inactive carrier state. The host genes related to DNA strand elongation showed significant difference between the immune clearance phase and inactive carrier state.
Conclusions:
By pairwise comparing the hepatic transcriptomes of CHB patients under a network view, several immune- and viral control-related pathways were identified in this study. These results might serve as a foundation for characterizing the host transcriptomes responded to CHB infection, and hold clues for the development of potential targets for disease control.
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