Multiomics Core

PROJECT SUMMARY/ ABSTRACT The Multiomics Core within the Hepatitis B HIV Cure Consortium (BICC) is committed to the development of advanced tools and methods to better understand the complex interplay of Hepatitis B virus (HBV) genomic diversity, the host immune response, and clinical outcomes among individuals co-infected with HIV. Central to the core's mission are three primary objectives: Aim 1 focuses on refining single molecule DNA sequencing techniques to better characterize HBV cccDNA and iDNA, even in low abundance samples. By adopting novel amplification techniques and integrating epigenetic mapping strategies, this aim intends to unravel the strategies HBV employs to circumvent immune detection, thereby highlighting potential therapeutic targets and the mechanisms and structures critical for HBV's survival and replication. Aim 2 seeks to enhance single molecule RNA sequencing protocols, focusing on improving efficiency and reducing costs. By leveraging advanced cell sorting techniques along with more affordable reagents, this objective facilitates an efficient comprehensive transcriptional profile of HBV-infected cells. Further, by incorporating single-cell proteomic data, we aim to resolve a rich, detailed perspective of virus-cell interaction, which may uncover new biomarkers or therapeutic targets. Aim 3 explores the application of graph-based bioinformatic methods to capture intra-host quasispecies diversity and construct a detailed map of HBV genomic diversity across the consortium's global cohorts. Exploration into phylogenetic methods leveraging genome graphs and recent advancements in single molecule sequencing may produce more robust approaches for understanding quasispecies diversity in relation to viral transmission dynamics, pathogenesis, treatment outcomes, and mechanisms of immune escape. Through these objectives, the core seeks to develop novel tools and methods that can advance our understanding into HBV, inform the development of targeted therapies, and ultimately improve the management and outcomes for individuals co-infected with HBV and HIV.