Integrative Bioinformatics Analysis of Proteins Associated with the Cardiorenal Syndrome

Abstract

The cardiorenal syndrome refers to the coexistence of kidney and cardiovascular disease, where cardiovascular events are the most common cause of death in patients with chronic kidney disease. Both, cardiovascular as well as kidney diseases have been extensively analyzed on a molecular level, resulting in molecular features and associated processes indicating a cross-talk of the two disease etiologies on a pathophysiological level. In order to gain a comprehensive picture of molecular factors contributing to the bidirectional interplay between kidney and cardiovascular system, we mined the scientific literature for molecular features reported as associated with the cardiorenal syndrome, resulting in 280 unique genes/proteins. These features were then analyzed on the level of molecular processes and pathways utilizing various types of protein interaction networks. Next to well established molecular features associated with the renin-angiotensin system numerous proteins involved in signal transduction and cell communication were found, involving specific molecular functions covering receptor binding with natriuretic peptide receptor and ligands as well known example. An integrated analysis of identified features pinpointed a protein interaction network involving mediators of hemodynamic change and an accumulation of features associated with the endothelin and VEGF signaling pathway. Some of these features may function as novel therapeutic targets.

Genomic convergence and network analysis approach to identify candidate genes in Alzheimer's disease

“…Further, network modelling of gene-gene and protein-protein interactions (PPI) provides a relatively new integrative approach to understand complex disease and identify disease-related genes [ 21 , 22 ]. For instance, candidate genes in complex disorders, such as AD [ 23 – 27 ], obstructive sleep apnea [ 28 ], heart failure [ 29 ], cancer [ 30 ] and cardiorenal syndrome [ 31 ], have already been explored extensively using PPI based approach. Thus, a convergent analysis approach involving multi-dimensional datasets combined with network or pathway analysis might serve as a comprehensive approach for disease candidate gene prioritization.…”

Deciphering keys genes in Cardio-renal Syndrome using network analysis

“…Peer-reviewed articles published in reputed journals were screened for key genes/proteins that are directly or indirectly associated with CRS. More than hundred (approx-104) publications published in between 2008 to 2020 covered a set of 119 non-redundant genes linked with CRS as described in Table 1 (see PDF) [ 20 - 117 ]. Out of them 54 CRS associated genes were reported in at least 5 articles.…”

Molecular models of the cardiorenal syndrome

“…Besides supportive data from conventional pathway enrichment analysis at the interface of CKD and CVD molecular models, further evidence also on a single feature level supports the presented concept. From the in total 223 molecular entities taking part in the interference model, 40 were explicitly discussed in previous work on the CRS . Among them 12 blood pressure regulating features play a role (as ACE, AGT) , naturally being of relevance for the cardiorenal axis .…”

“…A second concept is joint pathophysiology as for example, endothelial dysfunction, oxidative stress, or vascular inflammation, being causative for joint function decline of kidney and cardiovascular system . Integrative analysis of organ‐specific transcriptomics profiles together with molecular features identified as being CRS‐associated using scientific literature mining together with omics profiling data allowed addressing both aspects . Such analyses provided results on well established key processes as alterations in the activity of the renin–angiotensin system and mediators as the natriuretic peptide receptor and ligands.…”