Addressing data management and analysis challenges in viral genomics: The Swiss HIV cohort study viral next generation sequencing database.

Numerous HIV related outcomes can be determined on the viral genome, for example, resistance associated mutations, population transmission dynamics, viral heritability traits, or time since infection. Viral sequences of people with HIV (PWH) are therefore essential for therapeutic and research purposes. While in the first three decades of the HIV pandemic viral genomes were mainly sequenced using Sanger sequencing, the last decade has seen a shift towards next-generation sequencing (NGS) as the preferred method. NGS can achieve near full length genome sequence coverage and simultaneously, it accurately encapsulates the within-host diversity by characterizing HIV subpopulations. NGS opens new avenues for HIV research, but it also presents challenges concerning data management and analysis. We therefore set up the Swiss HIV Cohort Study Viral NGS Database (SHCND) to address key issues in the handling of NGS data including high loads of raw- and processed NGS data, data storage solutions, downstream application of sophisticated bioinformatic tools, high-performance computing resources, and reproducibility. The database is nested within the Swiss HIV Cohort Study (SHCS) and the Zurich Primary HIV Infection Cohort Study (ZPHI), which together enrolled 21,876 PWH since 1988 and include a biobank dating back to the early nineties. Since its initiation in 2018, the SHCND accumulated NGS sequences (plasma and proviral origin) of 5,178 unique PWH. We here describe the design, set-up, and use of this NGS database. Overall, the SHCND has contributed to several research projects on HIV pathogenesis, treatment, drug resistance, and molecular epidemiology, and has thereby become a central part of HIV-genomics research in Switzerland.