Rapid geographical source attribution of Salmonella enterica serovar Enteritidis genomes using hierarchical machine learning

Salmonella enterica serovar Enteritidis is one of the most frequent causes of Salmonel-losis globally and is commonly transmitted from animals to humans by the consumption of contam-inated foodstuffs. In the UK and many other countries in the Global North, a significant proportion of cases are caused by the consumption of imported food products or contracted during foreign travel, therefore, making the rapid identification of the geographical source of new infections a requirement for robust public health outbreak investigations. Herein, we detail the development and application of a hierarchical machine learning model to rapidly identify and trace the geographical source of S. Enteritidis infections from whole genome sequencing data. 2313 S. Enteritidis genomes, collected by the UKHSA between 2014–2019, were used to train a ‘local classifier per node’ hierarchical classifier to attribute isolates to four continents, 11 sub-regions, and 38 countries (53 classes). The highest classification accuracy was achieved at the continental level followed by the sub-regional and country levels (macro F1: 0.954, 0.718, 0.661, respectively). A number of countries commonly visited by UK travelers were predicted with high accuracy (hF1: >0.9). Longitudinal analysis and validation with publicly accessible international samples indicated that predictions were robust to prospective external datasets. The hierarchical machine learning framework provided granular geographical source prediction directly from sequencing reads in <4 min per sample, facili-tating rapid outbreak resolution and real-time genomic epidemiology. The results suggest additional application to a broader range of pathogens and other geographically structured problems, such as antimicrobial resistance prediction, is warranted.