Two additional anecdotes provide further credibility to our findi

Two additional anecdotes provide further credibility to our finding that HB 219 expression rate is a robust positive predictor of rosetting: First, we find that in all of the nine cases where there is rosettting data for an isolate that has HB 219 present in its most highly expressed sequence, considerable rosetting is see more observed

(defined as > 0.1). Secondly, we find that the DBLα domains of known rosetting var genes [30, 31] contain HB 219 (Additional file 1: Figure S2). Based on a comparison of the BIC scores of the models that result from the above variable selection procedures (Table  1), it seems that a more informative model for rosetting can be achieved when HB expression RG7420 chemical structure rates are used as candidate independent variables in addition to classic var types. More

specifically, the most informative model is achieved when we consider the expression rates of several HBs in addition to the expression rates of one classic var type: BS1/CP6. This becomes even clearer when we perform a fourth variable selection procedure using the principal A-1210477 components discussed below (row D in Table  1 and Additional file 3: Table S3). Principal components of HB expression rate profiles and variation in rosetting We perform a PCA on the HB expression rate profile, which we define as the set of expression rates for all 29 HBs. This deconstructs the HB expression rate profiles into orthogonal principal components (PCs) based on how they vary across different isolates. We then repeat the above network and variable selection analyses using PCs in place of individual HB expression rates (Additional file 1: Figures S11 and S12). We find that PC 1 is related to the cys2 versus non-cys2 distinction (Figure  5B), and that it captures the difference between HBs that are associated with severe versus mild spectrum phenotypes

(Figure  3; Additional file 1: Figure S4). PC 1 correlates with all of the severe spectrum phenotypes (Figure  5E) and the HB expression rates that contribute most to PC 1 are those with strong associations with disease phenotypes. PC 1 describes 8.15% of the variation among isolates with regard to their HB expression rates (Additional file 1: Figure S14). The HBs that have large Florfenicol positive values in PC 1 define the core of the mild spectrum linkage/phenotype subnetwork (Figures  3, 5A and D; Additional file 1: Figures S4 and S13). Likewise, the HB that has the dominant negative value in PC 1, HB 60, defines the core of the severe spectrum linkage/phenotype subnetwork (Figures  3, 5A and C; Additional file 1: Figures S4 and S13). These observations about PC 1 are robust to the specific isolates used for the PCA. When non-overlapping subsets of isolates are analyzed separately, the relative contributions of the various HB expression rates that primarily contribute to PC 1 remain essentially the same (Additional file 1: Figure S15). Figure 5 Principal components of HB expression rate profiles.

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