Engenharia reversa da rede regulatória da sepse pediátrica e identificação de reguladores mestres

Abstract

Sepsis is a acute inflammatory syndrome. Accountable for most obits in ICUs all over the world. Due to its multifactorial nature, there are few studies related to gene expression regulation in pediatric septic patients. Understanding the regulatory mechanisms of sepsis could help against sepsis and also help identify key points of signaling pathways responsible for disease progression. A good strategy to identify regulatory targets of a given disease is by reconstructing its regulatory network, as well as identify its possible master regulators. Given the lack of pediatric sepsis data and the huge difference between adult and pediatric immune response, the objective of this work is to reconstruct sepsis regulatory network and identify its putative master regulators. In summary, we found 15 transcription factors that have good chance of acting as master regulators in pediatric sepsis. Specially MEF2A, TRIM25 and RFX2 were identified upregulated in septic patients in comparison to healthy individuals. Each one of them have a distinct role, that was not directly related to sepsis. But, taken together, we hypothesize that they might act together to influenciate the disease prognosis. Results herein found points towards this three transcription factors as putative master regulators of pediatric sepsis. In vitro validation of the results found in silico could shed light in the different aspects of regulatory understanding of pediatric sepsis.