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Decoding Critical Targets and Signaling Pathways in EBV-Mediated Diseases Using Large Language Models.
Jingwen Yu1, Yaohao Wang1, Haidong Wang1
1School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen 518055, China.
Viruses
|November 27, 2024
Summary
Large language models analyzed Epstein-Barr virus (EBV) publications, revealing key host pathways and protein interactions. Findings identify diagnostic markers for diffuse large B-cell lymphoma and highlight EBV
Area of Science:
- Virology
- Oncology
- Bioinformatics
Background:
- Epstein-Barr virus (EBV) is a human oncovirus linked to numerous cancers.
- Understanding EBV-host interactions is vital for deciphering EBV-mediated pathogenesis.
- Current knowledge of these intricate molecular mechanisms remains incomplete.
Purpose of the Study:
- To leverage large language models (LLMs) for a comprehensive literature review of EBV-associated diseases.
- To elucidate EBV antigen-host pathway interactions and identify potential diagnostic and therapeutic targets.
- To create a functional encyclopedia of EBV-host interactions.
Main Methods:
- Screening of 36,105 EBV-relevant scientific publications using LLMs.
- Analysis of EBV-associated pathways, focusing on immune response, apoptosis, cell growth, and replication.
- Protein-protein interaction (PPI) network analysis to identify key EBV-related protein clusters.
- Validation of diagnostic markers and pathway correlations using integrated datasets.
Main Results:
- LLMs identified immune response, apoptosis, cell growth, and replication as key EBV-associated pathways.
- Three main EBV-related protein clusters were identified: TP53-centered apoptotic factors, EBV transcription factors, and immune response elements.
- BLLF3-targeted TLR2-associated factors show promise as diagnostic markers for diffuse large B-cell lymphoma (DLBCL).
- Co-expression of LMP1-targeted calcium pathway factors in Burkitt lymphoma (BL) was confirmed.
- Correlation and co-expression of LMP1-induced genes (PARP1, HIF1A, HK2) with glycolysis factors suggest LMP1 regulates glycolysis.
Conclusions:
- The study provides a comprehensive overview of EBV antigen-host pathway interactions across various malignancies.
- Identified diagnostic markers (e.g., BLLF3-targeted TLR2 factors for DLBCL) and pathway insights (e.g., LMP1's role in glycolysis) offer therapeutic potential.
- This LLM-driven approach establishes a valuable resource for future research and therapeutic strategy development in EBV-associated diseases.
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