Reverse engineering of sepsis regulatory network and identification of master regulators
Sepsis; regulatory networks; inflammatory diseases; master regulators
Sepsis is still a leading cause of death in ICUs all over the world. Its complexity makes it difficult to establish a consensus on genetic biomarkers and/or therapeutic targets. As there few studies regarding gene regulation in sepsis, the objective of this work is to reconstruct the sepsis regulatory network and find its Master Regulators (MRs). Here we used transcriptional data from public databases and bioinformatics pipelines to achieve the proposed results. We identified a set of 15 transcription factors as potential master regulators. These 15 master regulators are divided in two main clusters: TRIM25, RFX2 and MEF2A, and another composed by ZNF529, GATA3, KLF12, RORA, HOXB2, NR3C2, ZNF329, ZKSCAN8, ZNF331, ZNF235, ZNF234, ZNF134. We found that the master regulator expression has an unique pattern between clusters, especially for RFX2, TRIM25 and MEF2A. The majority of ZNF proteins in the bigger cluster led us to hypothesize the importance of this class of transcription factor to sepsis progression. This work aims to give a better understanding of transcription factors interaction in the disease progression, which may lead novel studies to identify potential therapeutic targets.