Project description:Rheumatic heart disease (RHD) continues to affect developing countries with low income, due to the lack of resources and effective diagnostic techniques. Understanding the genetic basis of progression from its prequel disease state, acute rheumatic fever (ARF), would aid in developing predictive biomarkers and improving patient care. To gain system-wide molecular insights into possible causes for progression, we collected blood transcriptomes from ARF (5) and RHD (5) patients. Using an integrated transcriptome and network analysis, we identified a subnetwork comprising the most significantly differentially expressed genes and most perturbed pathways in RHD as compared to ARF. For example, the chemokine signaling pathway was seen to be upregulated while tryptophan metabolism was found to be downregulated in RHD. The subnetworks of variation between the two conditions provide unbiased molecular-level insights into the host processes that may be associated with the progression of ARF to RHD, which has the potential to inform future diagnostics and therapeutic strategies. We also found significantly raised neutrophil/lymphocyte ratio in both ARF and RHD cohorts. Activated neutrophils and inhibited NK cell gene signatures reflected the drivers of the inflammatory process being common to both the disease conditions.