The Validation and Implications of Using Whole Genome Sequencing as a Replacement for Traditional Serotyping for a National Salmonella Reference Laboratory

Chris A. Yachison, Catherine Yoshida, James Robertson, John H. E. Nash, Peter Kruczkiewicz, Eduardo N. Taboada, Matthew Walker, Aleisha Reimer, Sara Christianson, Anil Nichani, The PulseNet Canada Steering Committee, Celine Nadon, Ana Paccagnella, Linda Hoang, Linda Chui, Paul Levett, Ryan McDonald, John Wylie, David Alexander, Vanessa Allen, Anne Maki, Sadjia Bekal, Ross Davidson, Elspeth Nickerson, Janet Reid, Laura Gilbert, Greg German, Moe Elmufti, Sean Quinlan, Cathy Carrillo, Ray Allain, Franco Pagotto, Lorelee Tschetter, Kim Ziebell

Salmonella serotyping remains the gold-standard tool for the classification of Salmonella isolates and forms the basis of Canada's national surveillance program for this priority foodborne pathogen. Public health officials have been increasingly looking toward whole genome sequencing (WGS) to provide a large set of data from which all the relevant information about an isolate can be mined. However, rigorous validation and careful consideration of potential implications in the replacement of traditional surveillance methodologies with WGS data analysis tools is needed. Two in silico tools for Salmonella serotyping have been developed, the Salmonella in silico Typing Resource (SISTR) and SeqSero, while seven gene MLST for serovar prediction can be adapted for in silico analysis. All three analysis methods were assessed and compared to traditional serotyping techniques using a set of 813 verified clinical and laboratory isolates, including 492 Canadian clinical isolates and 321 isolates of human and non-human sources. Successful results were obtained for 94.8, 88.2, and 88.3% of the isolates tested using SISTR, SeqSero, and MLST, respectively, indicating all would be suitable for maintaining historical records, surveillance systems, and communication structures currently in place and the choice of the platform used will ultimately depend on the users need. Results also pointed to the need to reframe serotyping in the genomic era as a test to understand the genes that are carried by an isolate, one which is not necessarily congruent with what is antigenically expressed. The adoption of WGS for serotyping will provide the simultaneous collection of information that can be used by multiple programs within the current surveillance paradigm; however, this does not negate the importance of the various programs or the role of serotyping going forward.