Identification of key regulators in Sarcoidosis through multidimensional systems biological approach

Abstract

Sarcoidosis is a multi-organ disorder where immunology, genetic and environmental factors play a key role in causing Sarcoidosis, but its molecular mechanism remains unclear. Identification of its genetics profiling that regulates the Sarcoidosis network will be one of the main challenges to understand its aetiology. We have identified differentially expressed genes (DEGs) by analyzing the gene expression profiling of Sarcoidosis and compared it with healthy control. Gene set enrichment analysis showed that these DEGs were mainly enriched in the inflammatory response, immune system, and pathways in cancer. Sarcoidosis protein interaction network was constructed by a total of 877 DEGs (up-down) and calculated its network topological properties, which follow hierarchical scale-free fractal nature up to six levels of the organization. We identified a large number of leading hubs that contain six key regulators (KRs) including ICOS, CTLA4, FLT3LG, CD33, GPR29 and ITGA4 are deeply rooted in the network from top to bottom, considering a backbone of the network. We identified the transcriptional factors (TFs) which are closely interacted with KRs. These genes and their TFs regulating the Sarcoidosis network are expected to be the main target for the therapeutic approaches and potential biomarkers. However, experimental validations of KRs needed to confirm their efficacy.

A bioinformatics approach to elucidate conserved genes and pathways in C. elegans as an animal model for cardiovascular research

“…The leading hubs have significantly important functions. They integrate the lower degree nodes for organizing and regulating activities like inter and intra-cross-talk among other essential genes, maintaining network properties and stability, and optimizing the network signal processing 63,64 .…”

Conserved Cardiovascular Network: Bioinformatics Insights into Genes and Pathways for EstablishingCaenorhabditis elegansas an Animal Model for Cardiovascular Diseases

“…Additionally, they contribute to sustaining network properties and stability, all while optimizing the processing of signals within the network. 65,66 .…”

Exome Sequencing Reveals Genetic Variability and Identifies Chronic Prognostic Loci in Chinese Sarcoidosis Patients

“…Two pathways were extracted from the KEGG analysis, including “hsa04380: osteoclast differentiation” (p-adjust = 0.0000587, gene count = 6) and “hsa04060: cytokine–cytokine receptor interaction” (p-adjust = 0.019641002, gene count = 5). A recent investigation of sarcoidosis illustrated that the differentially expressed genes (DEGs) identified by comparing the microarray datasets between sarcoidosis patients and healthy controls were significantly enriched in the positive regulation of protein kinase activity, osteoblast differentiation, and inflammatory response ( 47 ). The osteoclast differentiation and cytokine–cytokine receptor interaction pathways identified in our study may provide new ideas for understanding the role of immune-related gene pathways in Chinese sarcoidosis patients.…”

“…The leading hub genes with variants are also essential regulators due to their changes in the activities of proteins and regulation mechanisms ( 47 ). Based on the analysis of the top 10 hub genes among 30 immune-related candidate genes, we found that CCL4 and CXCR4 were the most significant interrelated genes.…”