Towards reliable whole genome sequencing for outbreak preparedness and response

Abstract

Background: To understand the dynamics of infectious diseases, genomic epidemiology is increasingly advocated, with a need for rapid generation of genetic sequences during outbreaks for public health decision making. Here, we explore the use of metagenomic sequencing compared to specific amplicon- and capture-based sequencing, both on the Nanopore and the Illumina platform for generation of whole genomes of Usutu virus, Zika virus, West Nile virus, and Yellow Fever virus. Results: We show that amplicon-based Nanopore sequencing can be used to rapidly obtain whole genome sequences in samples with a viral load up to Ct 33 and capture-based Illumina is the most sensitive method for initial virus determination. Conclusions: The choice of sequencing approach and platform is important for laboratories wishing to start whole genome sequencing. Depending on the purpose of genome sequencing the best choice can differ. The insights presented in this work and the shown differences in data characteristics can guide labs to make a well informed choice.