Fig. 4: TB lesion modular transcriptional signature correlates with TB clinical and microbiological characteristics revealing differential responses between patient’s group.

Modular analysis of RNA-seq data from TB lesions of 14 patients. Patients were clinically defined accordingly to sputum culture conversion (SCC) and TB disease impact on lung function, measured using the Saint George’s Respiratory Questionnaire (SGRQ) symptom score, as surrogates of treatment response and TB severity. Heatmap represent the key TB lesion modules significantly associated to individual’s’ clinical surrogates of TB severity and treatment response (a). Fold enrichments were calculated for each WGCNA module using hypergeometric distribution to assess whether the number of genes associated with each clinical status is larger than expected. Fold enrichment scores derived using QuSAGE are depicted, with red and blue indicating modules over or under expressed compared to the control. The colour intensity represents degree of perturbation. Modules with fold enrichment scored FDR p-value < 0.1 are considered significant. b, c show TB individuals’ stratification according to SCC (fast n = 28 or slow converters n = 20) and SGRQ symptom score (low impact if SGRQ < 20 with n = 23 or high impact if SGRQ > 20 with n = 25), respectively, and the significant association using their corresponding derived WGCNA significant eigengene modules (ME) (p < 0.05). Data are represented as median with an interquartile range (IQR). Boxplots show minimum and maximum values, the interquartile range (IQR, 25th to 75th percentile), and the whiskers representing 1.5 times the interquartile range. Outliers are indicated as individual points outside the whiskers. Statistical analysis was performed by applying the two-sided Wilcoxon-rank sum test. Source data are provided as a Source Data file.