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

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.

Use of dual genomic sequencing to screen mitochondrial diseases in pediatrics: a retrospective analysis

“…( 1234567890 www.nature.com/scientificreports/ used to determine the gene-disease association of MDs 21,22 . Dual genomic sequencing was a choice before the widespread use of whole genome sequencing, which was helpful for comprehensive diagnosis and establishment of a mitochondrial disease knowledge base 23 . MDs in children is mainly caused by nDNA variation, accounting for 75-95% 24,25 .…”

Database screening as a strategy to identify endogenous candidate metabolites to probe and assess mitochondrial drug toxicity

“…Nevertheless, a number of studies have demonstrated gene-mitochondrial disease associations that have led to the development of early clinical diagnosis assays which are used for routine newborn testing to identify inborn errors in metabolism 14 , 15 . Existing databases of centralized information, such as Gene Expression Omnibus (GEO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG), could be used to accelerate and improve the discovery of potential targets, biomarkers, and tracers that could aid in the assessment of mitochondrial-related ADRs 16 – 18 .…”

Recent advances in mitochondrial diseases: From molecular insights to therapeutic perspectives

“…Both genomes control the oxidative phosphorylation process and encode structural mitochondrial proteins. It was reported that the mitochondria contain approximately 1500 types of proteins, 13 of which are encoded by the mtDNA while the rest are encoded by nDNA ( Wang et al, 2021 ). In addition, the mtDNA contains 37 genes, which encode 22 mitochondrial-transfer RNAs (mt-tRNAs), 2 mitochondrial-ribosomal RNAs (mt-rRNA) and 13 OXPHOS protein subunits ( Alahmad et al, 2019 ).…”

“…Depending on the type of mitochondrial disease, severity of the symptoms, and organ affected, a person can live a near-normal life or suffer from a drastic change in their health that could lead to mortality. Mitochondrial diseases are governed mainly by mutations in the mtDNA and nDNA genomes that represent approximately 75% to 95% of all cases ( Wang et al, 2021 ). Additionally, a secondary mitochondrial dysfunction can occur due to other diseases, such as Alzheimer's, diabetes, and cancer, which are not caused by a genetic-related factor.…”