Coordinated modular functionality and prognostic potential of a heart failure biomarker-driven interaction network

We found that the structural and functional architecture of this PPI network is highly modular. These network modules can be assigned to specialized processes, specific cellular regions and their functional roles tend to partially overlap. Our results suggest that HF biomarkers may be defined as key coordinators of intra- and inter-module communication. Putative biomarkers can, in general, be distinguished as "information traffic" mediators within this network. The top high traffic proteins are encoded by genes that are not highly differentially expressed across HF and non-HF patients. Nevertheless, we present evidence that the integration of expression patterns from high traffic genes may support accurate prediction of HF. We quantitatively demonstrate that intra- and inter-module functional activity may be controlled by a family of transcription factors known to be associated with the prevention of hypertrophy.The systems-driven analysis reported here provides the basis for the identification of potentially novel biomarkers and understanding HF-related mechanisms in a more comprehensive and integrated way.Heart failure (HF) is a clinical syndrome that results from cardiac disease. HF can be characterized as the heart's inability to pump enough blood to meet physiological requirements. HF may be caused by cardiac injury (e.g. failure after myocardial infarction) or by non-ischemic diseases (e.g. dilated cardiomyopathy). Independently of the etiology, HF is known to be the by-product of a large-scale, dynamic interplay of proteins, hormones and metabolites. These interactions are in turn brought about and controlled by a diversity of genes and molecular pathways responsible for different processes, which range from inflammation trough extracellular-matrix remodeling to angiogenesis. This motivates the development of approaches to the systematic, integrated analysis of protein interactions related to HF.Many questions connected to the elucidation of the complex molec