Fig. 4

Epidemiological interpretation of deep-sequence phylogenetic data. a The 5 × 3 contingency table describes how deep-sequence phylogenetic patterns between two individuals were epidemiologically interpreted. Viral phylogenetic patterns between two individuals were summarized in terms of subgraph distance and subgraph topologies. There are five possible subgraph topologies between two individuals. All subgraphs of person 1 can be disconnected from the subgraphs of person 2 by another individual. If subgraphs of two individuals are adjacent, i.e. not disconnected by another individual, they can be consistently ancestral to each other in the same direction, intermingled in that some subgraphs are ancestral in one direction and others in the opposite direction, or siblings. The subgraph distance between viral subgraphs was stratified into ‘close’ (<0.025 substitutions per site), ‘intermediate’ (0.025–0.05 substitutions per site), and ‘distant’ (>0.05 substitutions per site) based on the couples’ analysis shown in Fig. 3a. Epidemiologic interpretations are indicated in colours. When only one sequence per individual is available, subgraphs of individuals correspond to the tips in a phylogeny, are either disconnected or siblings, and thus the direction of transmission is not inferable. b To determine the statistical support in inferences on transmission and the direction of transmission, analyses were repeated across the genome and the observed relationship types 1 → 2, 2 → 1, 1 ~ 2, G, U were counted (respectively denoted by k_1 → 2, k_2 → 1, k_1 ~ 2, k_G, k_U). To avoid overconfidence, an adjustment was made to account for the fact that overlapping windows are not statistically independent (see Supplementary Note 1). Evidence for no transmission between individuals 1 and 2 was estimated by \(\hat \mu _{12} = k_{\mathrm{U}}/n\); evidence for transmission between 1 and 2 was estimated by \(\hat \lambda _{12} = (k_{1 \to 2} + k_{1\sim 2} + k_{2 \to 1})/n\); and evidence for transmission from 1 to 2 given that transmission occurred between 1 and 2 was estimated by \({\hat{\mathrm \delta }}_{12} = k_{1 \to 2}/(k_{1 \to 2} + k_{2 \to 1})\); see Methods for further details