The impact of genomics implementation on a national enterics reference and surveillance laboratory

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Date
2017
Authors
Yachison, Christopher
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Publisher
Frontiers in Microbiology
Abstract
Foodborne disease surveillance in Canada is a multifaceted endeavor and human clinical disease is captured by two major laboratory-based surveillance systems, which monitor bacterial enteric pathogens, including Salmonella. For years, these programs have relied on multiple methodologies for the identification and subtyping of these bacterial pathogens. Recently, public health officials have been looking towards whole genome sequencing (WGS) to provide a large dataset from which all the relevant and predictable information about an isolate can be mined, thereby replacing traditional laboratory-based surveillance methodologies. Rigorous validation and careful implementation plans are required before WGS-based analyses can replace traditional subtyping tests. The objectives of this research were to assess the ability of WGS-based analysis methods to replace traditional subtyping tests used in laboratory-based surveillance systems and to develop the considerations that can guide future implementation of WGS technology. Salmonella serotyping remains the gold-standard tool for the classification of Salmonella isolates and the Salmonella in silico Typing Resource (SISTR) was validated using a set of 492 clinical isolates to uncover gaps in prediction algorithms and improve tool development. Following further refinement, traditional serotyping was compared to SISTR along with another in silico serotyping tool, SeqSero, and 7-gene multilocus sequence typing (MLST) for serovar prediction, which can be adapted for in silico analysis. Successful results were obtained for 94.8%, 88.2%, and 88.3% of the 813 clinical and laboratory isolates tested using SISTR, SeqSero, and 7-gene MLST, respectively. While the three methods vary in their algorithms, all would be suitable for maintaining the historical records, surveillance systems, and communication structures currently in place. Additionally, two WGS-based phylogenetic analysis methods, the Single Nucleotide Variant Phylogenomics (SNVPhyl) pipeline and whole genome MLST, were used to retrospectively assess a well characterized multi-serovar outbreak of Salmonella from 2014. While both platforms differ in their approaches for analyzing the WGS data, both methods reached the same conclusions and provided an increased resolution to the outbreak investigation. Additional non-outbreak clusters of disease were identified in the WGS analysis, and other PFGE-based clusters identified from this time period were further resolved or expanded to include more isolates than previously identified through PFGE. While WGS-based analysis offers many benefits, these technologies will transform the current surveillance systems for Salmonella, not only in Canada but around the world. However, these transformations should not be used to diminish the importance of the various surveillance programs, their mandates, and the need for multiple streams of evidence.
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Keywords
Whole genome sequencing, Salmonella enterica, Serotyping, Phylogenomics
Citation
Yachison C, Yoshida C, Robertson J, Nash JHE, Kruczkiewicz P, Taboada EN, Walker M, Reimer A, Christianson A, Nichani A, PulseNet Canada Steering Committee, Nadon C. 2017. The Validation and Implementation of Using Whole Genome Sequence as a Replacement for Traditional Serotyping for a National Salmonella Reference Laboratory. Front Microbiol; 8:1044. doi:10.3389/fmicb.2017.01044