The mining and construction of a knowledge base for gene-disease association in mitochondrial diseases

Wei Wang,Shujie Han,Lei Zhang,Yunfei Li,Junying Song,Mingming Shu,Wei Shang,Chunlan Song,Yunhai Chuai,Xinyu Zhai,Fu Chen,Shun Yao,Kexin Shen,Yayun Wang

doi:10.1038/s41598-021-03249-0

Abstract

Mitochondrial diseases are a group of heterogeneous genetic metabolic diseases caused by mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) gene mutations. Mining the gene-disease association of mitochondrial diseases is helpful for understanding the pathogenesis of mitochondrial diseases, for carrying out early clinical diagnosis for related diseases, and for formulating better treatment strategies for mitochondrial diseases. This project researched the relationship between genes and mitochondrial diseases, combined the Malacards, Genecards, and MITOMAP disease databases to mine the knowledge on mitochondrial diseases and genes, used database integration and the sequencing method of the phenolyzer tool to integrate disease-related genes from different databases, and sorted the disease-related candidate genes. Finally, we screened 531 mitochondrial related diseases, extracted 26,723 genes directly or indirectly related to mitochondria, collected 24,602 variant sites on 1474 genes, and established a mitochondrial disease knowledge base (MitDisease) with a core of genes, diseases, and variants. This knowledge base is helpful for clinicians who want to combine the results of gene testing for diagnosis, to understand the occurrence and development of mitochondrial diseases, and to develop corresponding treatment methods.

Highlights

Mitochondrial diseases are a group of heterogeneous genetic metabolic diseases caused by mitochondrial DNA or nuclear DNA gene mutations
In the MitDisease knowledge base, 531 mitochondrial diseases were screened by combining the MalaCards, GeneCards, and MITOMAP databases
Mitochondrial diseases are a group of heterogeneous genetic metabolic diseases caused by mitochondrial DNA or nuclear DNA gene m utations[13]

Summary

Introduction

Mitochondrial diseases are a group of heterogeneous genetic metabolic diseases caused by mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) gene mutations. Mining the gene-disease association of mitochondrial diseases is helpful for understanding the pathogenesis of mitochondrial diseases, for carrying out early clinical diagnosis for related diseases, and for formulating better treatment strategies for mitochondrial diseases This project researched the relationship between genes and mitochondrial diseases, combined the Malacards, Genecards, and MITOMAP disease databases to mine the knowledge on mitochondrial diseases and genes, used database integration and the sequencing method of the phenolyzer tool to integrate disease-related genes from different databases, and sorted the disease-related candidate genes. Mitochondrial diseases are caused by mitochondrial genome and (or) nuclear genome mutation, which leads to mitochondrial structural and functional defects and cell oxidative phosphorylation disorder. To research the relationship between genes and mitochondrial diseases, mining the knowledge on mitochondrial diseases and genes was carried out by combining the Malacards, Genecards, and MITOMAP disease databases, the phenolyzer tool was used to integrate disease-related genes from different databases and sort the disease-related candidate genes, and a knowledge base for gene-disease association in mitochondrial diseases was established, so as to systematically collect the information on mitochondrial disease, analyze the pathogenesis of related diseases, and provide a theoretical basis for the prevention and clinical treatment of mitochondrial diseases

Methods

Results

Conclusion