Decoding the similarities and specific differences between latent and active tuberculosis infections based on consistently differential expression networks

Abstract

Abstract Although intensive efforts have been devoted to investigating latent tuberculosis (LTB) and active tuberculosis (PTB) infections, the similarities and differences in the host responses to these two closely associated stages remain elusive, probably due to the difficulty in identifying informative genes related to LTB using traditional methods. Herein, we developed a framework known as the consistently differential expression network to identify tuberculosis (TB)-related gene pairs by combining microarray profiles and protein–protein interactions. We thus obtained 774 and 693 pairs corresponding to the PTB and LTB stages, respectively. The PTB-specific genes showed higher expression values and fold-changes than the LTB-specific genes. Furthermore, the PTB-related pairs generally had higher expression correlations and would be more activated compared to their LTB-related counterparts. The module analysis implied that the detected gene pairs tended to cluster in the topological and functional modules. Functional analysis indicated that the LTB- and PTB-specific genes were enriched in different pathways and had remarkably different locations in the NF-κB signaling pathway. Finally, we showed that the identified genes and gene pairs had the potential to distinguish TB patients in different disease stages and could be considered as drug targets for the specific treatment of patients with LTB or PTB.