Discriminating patients with influenza A virus infection from patients with bacterial infections. (A) Hierarchical clustering of 854 genes obtained from Mann-Whitney rank test comparison (P < .01) between 2 groups: influenza A (Inf A, 11 samples, green rectangle) and bacterial infections (red rectangle) with E coli (E.coli, 6 samples) or S pneumoniae (S.pn, 6 samples). Transformed expression levels are indicated by color scale, with red representing relatively high expression and blue indicating relatively low expression compared to the median expression for each gene across all donors. The black bar indicates IFN-inducible genes (IFN), and the red bar indicates genes involved in protein biosynthesis. Genes are listed in Table S2. (B) A supervised learning algorithm was used to identify 35 genes presenting the highest capacity to discriminate the 2 classes (Tables 1–2 and S3). Leave-one-out cross-validation of the training set with 35 genes classified the samples with 91% accuracy. The predicted class is indicated by light-colored solid rectangles (green for influenza A and red for bacteria). Two patients with bacterial infections were misclassified. (C) The 35 classifier genes thus identified were tested on an independent set of patients (open rectangles), including 7 new patients with influenza A (green), 23 with E coli, and 7 with S pneumoniae (red) infections. The 37 samples in this test set were classified with 95% accuracy (predicted class is indicated by light-colored rectangles). One patient was misclassified and one patient was indeterminate in class prediction (gray box). (D) The 35 classifier genes identified in panel B were tested on an independent set of patients (open squares), including 7 new patients with influenza A (Inf A), and 31 with S aureus infections. The 38 samples were classified with 87% accuracy.