Identification of Common Genes and Pathways in Eight Fibrosis Diseases.

Chang Gu,Xin Shi,Xuening Dang,Jiafei Chen,Xufeng Pan,Tao Huang,Yumei Chen,Chunji Chen

doi:10.3389/fgene.2020.627396

Abstract

Acute and chronic inflammation often leads to fibrosis, which is also the common and final pathological outcome of chronic inflammatory diseases. To explore the common genes and pathogenic pathways among different fibrotic diseases, we collected all the reported genes of the eight fibrotic diseases: eye fibrosis, heart fibrosis, hepatic fibrosis, intestinal fibrosis, lung fibrosis, pancreas fibrosis, renal fibrosis, and skin fibrosis. We calculated the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment scores of all fibrotic disease genes. Each gene was encoded using KEGG and GO enrichment scores, which reflected how much a gene can affect this function. For each fibrotic disease, by comparing the KEGG and GO enrichment scores between reported disease genes and other genes using the Monte Carlo feature selection (MCFS) method, the key KEGG and GO features were identified. We compared the gene overlaps among eight fibrotic diseases and connective tissue growth factor (CTGF) was finally identified as the common key molecule. The key KEGG and GO features of the eight fibrotic diseases were all screened by MCFS method. Moreover, we interestingly found overlaps of pathways between renal fibrosis and skin fibrosis, such as GO:1901890-positive regulation of cell junction assembly, as well as common regulatory genes, such as CTGF, which is the key molecule regulating fibrogenesis. We hope to offer a new insight into the cellular and molecular mechanisms underlying fibrosis and therefore help leading to the development of new drugs, which specifically delay or even improve the symptoms of fibrosis.

Highlights

Acute and chronic inflammation often leads to fibrosis, which is the common and final pathological outcome of chronic inflammatory diseases (Rockey et al, 2015)
We compared the reported genes of the eight fibrotic diseases using R package SuperExactTest,1 which has the function of identification of sets of objects with shared features, which is a common operation in all disciplines
connective tissue growth factor (CTGF) was identified as the common regulatory gene in the eight kinds of fibrotic diseases by Monte Carlo feature selection (MCFS) method

Summary

INTRODUCTION

Acute and chronic inflammation often leads to fibrosis, which is the common and final pathological outcome of chronic inflammatory diseases (Rockey et al, 2015). The wound healing in the fibrotic tissue is regulated by complex processes within different cells, and some specific molecular pathways are activated. We proposed a new computational method incorporating feature engineering and feature selection algorithms to explore the common controlling genes and corresponding pathways among eight different organs’ fibrosis. The key genes and pathways were revealed, and the cross-talks between diseases were investigated. These results were helpful for understanding the molecular mechanisms of fibrosis diseases and finding new therapeutic indications of existing drugs, i.e., drug repositioning

MATERIALS AND METHODS

DISCUSSION

Findings

DATA AVAILABILITY STATEMENT