Abstract
BackgroundThe hepatitis B virus (HBV) is one of the main causes of viral hepatitis and liver cancer. HBV integration is one of the key steps in the virus-promoted malignant transformation.ResultsAn attention-based deep learning model, DeepHBV, was developed to predict HBV integration sites. By learning local genomic features automatically, DeepHBV was trained and tested using HBV integration site data from the dsVIS database. Initially, DeepHBV showed an AUROC of 0.6363 and an AUPR of 0.5471 for the dataset. The integration of genomic features of repeat peaks and TCGA Pan-Cancer peaks significantly improved model performance, with AUROCs of 0.8378 and 0.9430 and AUPRs of 0.7535 and 0.9310, respectively. The transcription factor binding sites (TFBS) were significantly enriched near the genomic positions that were considered. The binding sites of the AR-halfsite, Arnt, Atf1, bHLHE40, bHLHE41, BMAL1, CLOCK, c-Myc, COUP-TFII, E2A, EBF1, Erra, and Foxo3 were highlighted by DeepHBV in both the dsVIS and VISDB datasets, revealing a novel integration preference for HBV.ConclusionsDeepHBV is a useful tool for predicting HBV integration sites, revealing novel insights into HBV integration-related carcinogenesis.
Highlights
The hepatitis B virus (HBV) is one of the main causes of viral hepatitis and liver cancer
HBV integration sequences were prepared according to HBV integration sites as positive samples, following the steps in the method
DeepHINT, an existing deep learning model for predicting HIV integration sites according to the surroundings [18], was evaluated using HBV integration sequences for training and testing
Summary
The hepatitis B virus (HBV) is one of the main causes of viral hepatitis and liver cancer. HBV integration is one of the key steps in the virus-promoted malignant transformation. HBV is the main cause of viral hepatitis and liver cancer (HCC) [1]. HBV can integrate into the host genome via an RNA intermediate due to its small size [1]. Cases of viral DNA integrated into the human genome were detected in 85–90% of HBV-related HCCs [2]. HBV attaches and enters hepatocytes, transports its nucleocapsid, which contains a relaxed circular DNA (rcDNA), to the host nucleus. Further analysis revealed an association between HBV integration and genomic instability during these insertional events [8]. HBV integration was reported to recur in the telomerase reverse
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