The Salmonella In Silico Typing Resource (SISTR): An Open Web-Accessible Tool for Rapidly Typing and Subtyping Draft Salmonella Genome Assemblies

Abstract

For nearly 100 years serotyping has been the gold standard for the identification of Salmonella serovars. Despite the increasing adoption of DNA-based subtyping approaches, serotype information remains a cornerstone in food safety and public health activities aimed at reducing the burden of salmonellosis. At the same time, recent advances in whole-genome sequencing (WGS) promise to revolutionize our ability to perform advanced pathogen characterization in support of improved source attribution and outbreak analysis. We present the Salmonella In Silico Typing Resource (SISTR), a bioinformatics platform for rapidly performing simultaneous in silico analyses for several leading subtyping methods on draft Salmonella genome assemblies. In addition to performing serovar prediction by genoserotyping, this resource integrates sequence-based typing analyses for: Multi-Locus Sequence Typing (MLST), ribosomal MLST (rMLST), and core genome MLST (cgMLST). We show how phylogenetic context from cgMLST analysis can supplement the genoserotyping analysis and increase the accuracy of in silico serovar prediction to over 94.6% on a dataset comprised of 4,188 finished genomes and WGS draft assemblies. In addition to allowing analysis of user-uploaded whole-genome assemblies, the SISTR platform incorporates a database comprising over 4,000 publicly available genomes, allowing users to place their isolates in a broader phylogenetic and epidemiological context. The resource incorporates several metadata driven visualizations to examine the phylogenetic, geospatial and temporal distribution of genome-sequenced isolates. As sequencing of Salmonella isolates at public health laboratories around the world becomes increasingly common, rapid in silico analysis of minimally processed draft genome assemblies provides a powerful approach for molecular epidemiology in support of public health investigations. Moreover, this type of integrated analysis using multiple sequence-based methods of sub-typing allows for continuity with historical serotyping data as we transition towards the increasing adoption of genomic analyses in epidemiology. The SISTR platform is freely available on the web at https://lfz.corefacility.ca/sistr-app/.

Application of Whole-Genome Sequencing Data for O-Specific Antigen Analysis and In Silico Serotyping of Pseudomonas aeruginosa Isolates

“…Importantly, since the frequency of nontypeability of in vitro serotyped P. aeruginosa isolates may amount to Ͼ65% (10), analysis with PAst is clearly advantageous and superior compared to conventional in vitro serotyping. Importantly, the superiority of the PAst tool as a reliable and fast typing method is consistent with that of other published tools for in silico serotyping (31)(32)(33)(34)(35). Similar to SerotypeFinder (in silico serotyping of Escherichia coli) (31), LisSero (in silico serotyping of Listeria monocytogenes) (34,35), and SeqSero (in silico serotyping of Salmonella) (32), PAst resolves the OSA cluster information to the most accurate typing possible as a serogroup representing 1 to 3 serotypes.…”

Navigating Microbiological Food Safety in the Era of Whole-Genome Sequencing

“…SeqSero is a web application that is able to determine the serotype of Salmonella isolates from both raw sequencing reads and whole-genome assemblies with an accuracy of 92 to 99% (108). The Salmonella In Silico Typing Resource (SISTR) is an online platform that allows users to upload assembled genomic data and then predicts the serotype (with 94.6% accuracy), performs MLST and cgMLST, and allows users to view their sequence in a broad phylogenetic context (109). While this software currently provides typing information, it is also being updated to provide AMR profiling and detect virulence genes (109).…”

“…The Salmonella In Silico Typing Resource (SISTR) is an online platform that allows users to upload assembled genomic data and then predicts the serotype (with 94.6% accuracy), performs MLST and cgMLST, and allows users to view their sequence in a broad phylogenetic context (109). While this software currently provides typing information, it is also being updated to provide AMR profiling and detect virulence genes (109). The Metric-Orientated Sequence Typer can also estimate a serovar on the basis of a short-read sequence, but users must download the program from github and run it from a command line interface, making it less accessible (110).…”

A Primer on Infectious Disease Bacterial Genomics

“…Thus, gene-by-gene approaches are particularly useful for integration of newly sequenced data into a global context. To date, use of wgMLST/cgMLST methods has been limited to custom schemata developed and curated for individual sequencing projects (193,195), free Web services specific to a particular organism (200), or large institutions (175). However, with commitment by some, such as the CDC (175), to expand availability of wgMLST tools, these methods will become more and more relevant in the near future.…”

“…Furthermore, the ability to mine WGS data and extract multiple typing schemes makes global comparisons achievable, which is essential for global surveillance and epidemiological investigations. For example, the SISTR platform (200) uses WGS draft assemblies to rapidly extract multiple typing schemes, including both molecular (MLST) and phenotypic (serotyping) schemes.…”