In the management of infectious disease outbreaks, grouping cases into clusters and understanding their underlying epidemiology are fundamental tasks. In genomic epidemiology, clusters are typically identified either using pathogen sequences alone or with sequences in combination with epidemiological data such as location and time of collection. However, it may not be feasible to culture and sequence all pathogen isolates, so sequence data may not be available for all cases. This presents challenges for identifying clusters and understanding epidemiology, because these cases may be important for transmission. Demographic, clinical and location data are likely to be available for unsequenced cases, and comprise partial information about their clustering. Here, we use statistical modelling to assign unsequenced cases to clusters already identified by genomic methods, assuming that a more direct method of linking individuals, such as contact tracing, is not available. We build our model on pairwise similarity between cases to predict whether cases cluster together, in contrast to using individual case data to predict the cases' clusters. We then develop methods that allow us to determine whether a pair of unsequenced cases are likely to cluster together, to group them into their most probable clusters, to identify which are most likely to be members of a specific (known) cluster, and to estimate the true size of a known cluster given a set of unsequenced cases. We apply our method to tuberculosis data from Valencia, Spain. Among other applications, we find that clustering can be predicted successfully using spatial distance between cases and whether nationality is the same. We can identify the correct cluster for an unsequenced case, among 38 possible clusters, with an accuracy of approximately 35 %, higher than both direct multinomial regression (17 %) and random selection (< 5 %).
Keywords: TB cases; genomic clustering.