Approaches and challenges to inferring the geographical source of infectious disease outbreaks using genomic data

Genomic data hold increasing potential in the elucidation of transmission dynamics and geographical sources of infectious disease outbreaks. Phylogeographic methods that use epidemiological and genomic data obtained from surveillance enable us to infer the history of spatial transmission that is naturally embedded in the topology of phylogenetic trees as a record of the dispersal of infectious agents between geographical locations. In this Review, we provide an overview of phylogeographic approaches widely used for reconstructing the geographical sources of outbreaks of interest. These approaches can be classified into ancestral trait or state reconstruction and structured population models, with structured population models including popular structured coalescent and birth-death models. We also describe the major challenges associated with sequencing technologies, surveillance strategies, data sharing, and analysis frameworks that became apparent during the generation of large-scale genomic data in recent years, extending beyond inference approaches. Finally, we highlight the role of genomic data in geographical source inference and clarify how this enhances understanding and molecular investigations of outbreak sources.