Procedures to analyze combined modifications for different incorrect predictions. Each network realization included one modification for every incorrect prediction. A plausible network realization satisfied the following criteria: 1) the network contained no contradictory modification, and, after the combined modifications to iNJ 661m were applied, 2) the wild-type growth rate (calculated from flux balance analysis) was greater than the minimal rate (taken to be 0.027 h-1 according the growth rate of M. tuberculosis in mouse macrophages ), 3) incorrect predictions were corrected, and 4) existing correct predictions before the applied modification were still correct. Finally, from all plausible network realizations, we selected the networks that were associated with minimum adjustment. TN, true negative; TP, true positive; FN, false negative; TN, true negative; Y, yes; N, no.