Opportunities for using PacBio Long-read Sequencing for COVID-19 Research

Scientists worldwide are actively working to tame the COVID-19 pandemic by developing therapies for patients with severe disease and a vaccine to stem transmission. Accomplishing these two goals will require high resolution genetic information on both the SARS-Cov-2 virus and the host response to infection, beyond what suffices for diagnostic testing.

PacBio highly accurate long-read sequencing data is one tool scientists can use in their COVID-19 research. PacBio sequencing is unique in that it produces HiFi reads that are both long (up to 15 kb) and have very high base-level accuracy (>99.9%). These qualities are advantageous for applications that require phasing of SNVs across DNA amplicons and for resolving individual variants within complex populations of highly similar sequences. For example, in order to develop a broadly efficacious therapeutic or vaccine, scientists will need to understand how SARS-CoV-2 evolves within a host, over time in a community, and across geographic regions. An examination of currently public SARS-CoV-2 genomes shows how challenging getting high quality data can be with other sequencing approaches. Similarly, when mining the immune repertoire of recovered patients for therapeutics, researchers will need accurate and complete information on B cell receptors that can carry SNVs and indels along the entire length of the variable region. Furthermore, PacBio sequencing can directly detect and phase the germline IGH locus from which B cell receptors are derived, allowing researchers to connect phenotype to genotype without inference. In this presentation, we will discuss what PacBio sequencing can offer COVID-19 researchers as they strive to understand the biology underlying this global pandemic.

Learning Objectives:

1. Understanding how highly accurate long reads can be used to obtain high quality SARS-CoV-2 genomes with no gaps, and how this connects to virus research goals

2. Understand how highly accurate long reads can be used to understand the host immune response to SARS-CoV-2 infection.