Information encoded in a network of inflammation proteins predicts clinical outcome after myocardial infarction

We assembled My-Inflamome, a network of protein interactions related to inflammation and prognosis in MI. We established associations between network properties, disease biology and capacity to distinguish between prognostic categories. The latter was tested with classification models built on blood-derived microarray data from post-MI patients with different outcomes. This was followed by experimental verification of significant associations.My-Inflamome is organized into modules highly specialized in different biological processes relevant to heart repair. Highly connected proteins also tend to be high-traffic components. Such bottlenecks together with genes extracted from the modules provided the basis for novel prognostic models, which could not have been uncovered by standard analyses. Modules with significant involvement in transcriptional regulation are targeted by a small set of microRNAs. We suggest a new panel of gene expression biomarkers (TRAF2, SHKBP1 and UBC) with high discriminatory capability. Follow-up validations reported promising outcomes and motivate future research.This study enhances understanding of the interaction network that executes inflammatory responses in human MI. Network-encoded information can be translated into knowledge with potential prognostic application. Independent evaluations are required to further estimate the clinical relevance of the new prognostic genes.Cardiovascular disease is a major cause of death worldwide. Myocardial infarction (MI) often leads to heart failure (HF), which makes MI a leading source of morbidity and hospitalizations [1]. Different inflammation biomarkers with diagnostic and prognostic applications have been deployed in the clinical setting [2,3]. Post-MI cell death triggers the activation of several complex inflammatory processes to clear dead cells and initiate heart tissue regeneration [4-7]. It has been suggested that such a coordinated regulation is fundamental to enable cardiac repair and reco