Individual-based simulations were used to assess the efficacy of our method for reconstructing transmission trees from outbreak genetic data. All simulations were performed using the R software, and procedures that we implemented in the adegenet package. The simulation system is further described in Supplementary Information. We first used simulations to compare SeqTrack to classical phylogenetic reconstruction. Because the outputs of both approaches are very different (phylogenies do not provide ancestries between tips), we could not proceed to systematic comparisons over a large number of data sets. However, while not quantitative, the comparisons we performed can be used to show the fundamental differences between both approaches. We simulated two simple genealogies of isolates, using haplotypes of 10 000 nucleotides and a mutation rate of 10 À4 mutation per nucleotide and generation, over three and four generations, respectively (Figures 2a and 3a ). In the second data set (Figure 3) , only a portion of the genealogy was sampled, so as to show the behaviors of the methods for inferring ancestries with unsampled ancestors. Note that the two data sets were chosen randomly, and the results were qualitatively similar in all other simulations we examined. SeqTrack was used to obtain maximum parsimony genealogies (Figures 2b and 3b) . A classical phylogeny was obtained by neighbor-joining using pairwise nucleotidic distances between sampled isolates (Figures 2c and 3c) . To give the neighbor-joining phylogenetic trees the right direction, trees were rooted using the most ancient isolate sampled. We also analyzed these data using temporally informed phylogenetic reconstruction as implemented in the BEAST software (Drummond and Rambaut, 2007; Figures 2d and 3d) . We used the exponential growth model with strict molecular clock model, keeping other parameters to their default settings. A consensus phylogeny was computed on the 5000 last simulated trees.