Genomics and outbreak investigation: from sequence to consequence

Abstract

Outbreaks of infection can be devastating for individuals and societies. In this review, we examine the applications of new high-throughput sequencing approaches to the identification and characterization of outbreaks, focusing on the application of whole-genome sequencing (WGS) to outbreaks of bacterial infection. We describe traditional epidemiological analysis and show how WGS can be informative at multiple steps in outbreak investigation, as evidenced by many recent studies. We conclude that high-throughput sequencing approaches can make a significant contribution to the investigation of outbreaks of bacterial infection and that the integration of WGS with epidemiological investigation, diagnostic assays and antimicrobial susceptibility testing will precipitate radical changes in clinical microbiology and infectious disease epidemiology in the near future. However, several challenges remain before WGS can be routinely used in outbreak investigation and clinical practice.

Figure 1

Whole-genome sequencing delivers high-resolution typing and insights into pathogen biology. In this hypothetical example, the two large ovals represent sets of isolates (small ovals) that have been assigned to genotypes using conventional laboratory typing. Clouds indicate clusters within those genotypes built using epidemiological data. Whole-genome sequencing provides a more detailed view of pathogen epidemiology, revealing previously unseen links (red lines) between genome-sequenced isolates (filled small ovals) within and between genotypes. Whole-genome sequencing also provides insights into pathogen biology, including the factors associated with virulence (represented here by toxin gene X) and drug resistance (represented here by resistance gene Y).