Impacts and shortcomings of genetic clustering methods for infectious disease outbreaks

For infectious diseases, a genetic cluster is a group of closely related infections that is usually interpreted as representing a recent outbreak of transmission. Genetic clustering methods are becoming increasingly popular for molecular epidemiology, especially in the context of HIV where there is now considerable interest in applying these methods to prioritize groups for public health resources such as pre-exposure prophylaxis. To date, genetic clustering has generally been performed with ad hoc algorithms, only some of which have since been encoded and distributed as free software. These algorithms have seldom been validated on simulated data where clusters are known, and their interpretation and similarities are not transparent to users outside of the field. Here, I provide a brief overview on the development and inter-relationships of genetic clustering methods, and an evaluation of six methods on data simulated under an epidemic model in a risk-structured population. The simulation analysis demonstrates that the majority of clustering methods are systematically biased to detect variation in sampling rates among subpopulations, not variation in transmission rates. I discuss these results in the context of previous work and the implications for public health applications of genetic clustering.