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Protein-protein interaction network analysis of cirrhosis liver disease.

ABSTRACT: AIM:Evaluation of biological characteristics of 13 identified proteins of patients with cirrhotic liver disease is the main aim of this research. BACKGROUND:In clinical usage, liver biopsy remains the gold standard for diagnosis of hepatic fibrosis. Evaluation and confirmation of liver fibrosis stages and severity of chronic diseases require a precise and noninvasive biomarkers. Since the early detection of cirrhosis is a clinical problem, achieving a sensitive, specific and predictive novel method based on biomarkers is an important task. METHODS:Essential analysis, such as gene ontology (GO) enrichment and protein-protein interactions (PPI) was undergone EXPASy, STRING Database and DAVID Bioinformatics Resources query. RESULTS:Based on GO analysis, most of proteins are located in the endoplasmic reticulum lumen, intracellular organelle lumen, membrane-enclosed lumen, and extracellular region. The relevant molecular functions are actin binding, metal ion binding, cation binding and ion binding. Cell adhesion, biological adhesion, cellular amino acid derivative, metabolic process and homeostatic process are the related processes. Protein-protein interaction network analysis introduced five proteins (fibroblast growth factor receptor 4, tropomyosin 4, tropomyosin 2 (beta), lectin, Lectin galactoside-binding soluble 3 binding protein and apolipoprotein A-I) as hub and bottleneck proteins. CONCLUSION:Our result indicates that regulation of lipid metabolism and cell survival are important biological processes involved in cirrhosis disease. More investigation of above mentioned proteins will provide a better understanding of cirrhosis disease.

SUBMITTER: Safaei A

PROVIDER: S-EPMC4833850 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Protein-protein interaction network analysis of cirrhosis liver disease.

Safaei Akram A Rezaei Tavirani Mostafa M Arefi Oskouei Afsaneh A Zamanian Azodi Mona M Mohebbi Seyed Reza SR Nikzamir Abdol Rahim AR

Gastroenterology and hepatology from bed to bench 20160101 2

<h4>Aim</h4>Evaluation of biological characteristics of 13 identified proteins of patients with cirrhotic liver disease is the main aim of this research.<h4>Background</h4>In clinical usage, liver biopsy remains the gold standard for diagnosis of hepatic fibrosis. Evaluation and confirmation of liver fibrosis stages and severity of chronic diseases require a precise and noninvasive biomarkers. Since the early detection of cirrhosis is a clinical problem, achieving a sensitive, specific and predi ...[more]

PMID: 27099671

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Project description:AIM:In the current study, we analysised only the articles that investigate serum proteome profile of cirrhosis patients or HCC patients versus healthy controls. BACKGROUND:Increased understanding of cancer biology has enabled identification of molecular events that lead to the discovery of numerous potential biomarkers in diseases. Protein-protein interaction networks is one of aspect that could elevate the understanding level of molecular events and protein connections that lead to the identification of genes and proteins associated with diseases. METHODS:Gene expression data, including 63 gene or protein names for hepatocellular carcinoma and 29 gene or protein names for cirrhosis, were extracted from a number of previous investigations. The networks of related differentially expressed genes were explored using Cytoscape and the PPI analysis methods such as MCODE and ClueGO. Centrality and cluster screening identified hub genes, including APOE, TTR, CLU, and APOA1 in cirrhosis. RESULTS:CLU and APOE belong to the regulation of positive regulation of neurofibrillary tangle assembly. HP and APOE involved in cellular oxidant detoxification. C4B and C4BP belong to the complement activation, classical pathway and acute inflammation response pathway. Also, it was reported TTR, TFRC, VWF, CLU, A2M, APOA1, CKAP5, ZNF648, CASP8, and HSP27 as hubs in HCC. In HCC, these include A2M that are corresponding to platelet degranulation, humoral immune response, and negative regulation of immune effector process. CLU belong to the reverse cholesterol transport, platelet degranulation and human immune response. APOA1 corresponds to the reverse cholesterol transport, platelet degranulation and humoral immune response, as well as negative regulation of immune effector process pathway. CONCLUSION:In conclusion, this study suggests that there is a common molecular relationship between cirrhosis and hepatocellular cancer that may help with identification of target molecules for early treatment that is essential in cancer therapy.

Project description:BackgroundInfectious diseases are a cruel assassin with millions of victims around the world each year. Understanding infectious mechanism of viruses is indispensable for their inhibition. One of the best ways of unveiling this mechanism is to investigate the host-pathogen protein-protein interaction network. In this paper we try to disclose many properties of this network. We focus on human as host and integrate experimentally 32,859 interaction between human proteins and virus proteins from several databases. We investigate different properties of human proteins targeted by virus proteins and find that most of them have a considerable high centrality scores in human intra protein-protein interaction network. Investigating human proteins network properties which are targeted by different virus proteins can help us to design multipurpose drugs.ResultsAs host-pathogen protein-protein interaction network is a bipartite network and centrality measures for this type of networks are scarce, we proposed seven new centrality measures for analyzing bipartite networks. Applying them to different virus strains reveals unrandomness of attack strategies of virus proteins which could help us in drug design hence elevating the quality of life. They could also be used in detecting host essential proteins. Essential proteins are those whose functions are critical for survival of its host. One of the proposed centralities named diversity of predators, outperforms the other existing centralities in terms of detecting essential proteins and could be used as an optimal essential proteins' marker.ConclusionsDifferent centralities were applied to analyze human protein-protein interaction network and to detect characteristics of human proteins targeted by virus proteins. Moreover, seven new centralities were proposed to analyze host-pathogen protein-protein interaction network and to detect pathogens' favorite host protein victims. Comparing different centralities in detecting essential proteins reveals that diversity of predator (one of the proposed centralities) is the best essential protein marker.

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Protein-protein interaction network analysis of cirrhosis liver disease.

Publications

Protein-protein interaction network analysis of cirrhosis liver disease.

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