Celiac disease and hepatitis C relationships in transcriptional regulatory networks

Abstract

Aim: we mainly aimed to elucidate potential comorbidities between celiac disease and hepatitis c by means of data and network analysis approaches.

Background: understanding the association among the disorders evidently has important impact on the diagnosis and therapeutic approaches. Celiac disease is the most challenging, common types of autoimmune disorders. On the other hand, hepatitis c virus genome products like some proteins are supposed to be resemble to gliadin types that in turn activates gluten intolerance in people with inclined to gluten susceptibilities. Moreover, a firm support of association between chronic hepatitis and celiac disease remains largely unclear. Henceforth exploring cross-talk among these diseases will apparently lead to the promising discoveries concerning important genes and regulators.

Methods: 321 and 1032 genes associated with celiac disease and hepatitis c retrieved from DisGeNET were subjected to build a gene regulatory network. Afterward a network-driven integrative analysis was performed to exploring prognosticates genes and related pathways.

Results: 105 common genes between these diseases included 11 transcription factors were identified as hallmark molecules where by further screening enriched in biological GO terms and pathways chiefly in immune systems and signaling pathways such as chemokines, cytokines and interleukins.

Conclusion: in silico data analysis approaches indicated that the identified selected combinations of genes covered a wide range of known functions triggering the inflammation implicated in these diseases.

Keywords: celiac disease; hepatitis c; regulatory network.

Figure 1

Venn diagram of intersection between celiac disease, hepatitis c related genes retrieved from DisGeNET server and TRRUST regulatory links . Ultimately, 105 genes were taken as CD-HCV specific genes which are being in turn regulated by trascription factors based on the experimentally validated gene-TF links in TRRUST database

Figure 2

Interaction network established by common genes underlying celiac disease and hepatitis c. the green and red colors show genes and transcription factors respectively. Network units with more connectivity have been illustrated bigger.→ and ┴ arrows show the activation and repression effects of a TF on the targeted genes respectively

Figure 3

Biological pathways in which common genes extracted from celiac disease and hepatitis c potentially involved by Reactom server with default parameters. The bars have been arranged top to down illustrating the number of genes and significance level assigned to each pathway

Figure 4

Functional classification of biological processes in which differential expressed genes from common genes associated to celiac disease and hepatitis c supposed to be involved. The GO terms considered significant based on hypergeometric test with Benjamini and Hochberg FDR correction and significance level 0.01 by BINGO app. The bars have been arranged top to down illustrating the number of genes and significance level assigned to each GO term

Figure 5

A, interacting miRNAs with the upstream motifs in common genes underlying celiac disease and hepatitis c retrieved from TargetScan. B, experimentally validated targets of explored miRNAs using miRWalk