Elucidating the roles of SOD3 correlated genes and reactive oxygen species in rare human diseases using a bioinformatic-ontology approach

• Published in: PloS one Vol. 19; no. 10; p. e0313139
• Main Authors: Stanworth, Mark, Zhang, Shu-Dong
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.10.2024; Public Library of Science (PLoS)
• Subjects: ADNP protein; Amino acids; Analysis; Aquaporins; Binding sites; Biology and Life Sciences; Biomarkers; Cancer; Colorectal cancer; Computational biology; Computational Biology - methods; Connective tissue diseases; Connective tissues; Copper; Correlation analysis; Disease; Disorders; Ehlers-Danlos syndrome; Elastin microfibril interface located protein; Extracellular matrix; Gene expression; Gene Ontology; Genes; Genetic disorders; Genomic analysis; Glaucoma; Holt-Oram syndrome; Humans; Hydrogen peroxide; Literature reviews; Medical prognosis; Medicine and Health Sciences; Metabolites; Neuropathy; Normal distribution; Ontology; Oxidative stress; Oxidative Stress - genetics; Oxygen; Phenotypes; Properties; Rare diseases; Rare Diseases - genetics; Rare species; Reactive oxygen species; Reactive Oxygen Species - metabolism; Retinoblastoma; Smooth muscle; Software; Species diffusion; Superoxide dismutase; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Therapeutic targets; Ireland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0313139

Superoxide Dismutase 3 (SOD3) scavenges extracellular superoxide giving a hydrogen peroxide metabolite. Both Reactive Oxygen Species diffuse through aquaporins causing oxidative stress and biomolecular damage. SOD3 is differentially expressed in cancer and this research utilises Gene Expression Omnibus data series GSE2109 with 2,158 cancer samples. Genome-wide expression correlation analysis was conducted with SOD3 as the seed gene. Categorical SOD3 Pearson Correlation gene lists incrementing in correlation strength by 0.01 from ρ≥|0.34| to ρ≥|0.41| were extracted from the data. Positively and negatively SOD3 correlated genes were separated for each list and checked for significance against disease overlapping genes in the ClinVar and Orphanet databases via Enrichr. Disease causal genes were added to the relevant gene list and checked against Gene Ontology, Phenotype Ontology, and Elsevier Pathways via Enrichr before the significant ontologies containing causal and non-overlapping genes were reviewed with a literature search for possible disease and oxidative stress associations. 12 significant individually discriminated disorders were identified: Autosomal Dominant Cutis Laxa (p = 6.05x10 -7 ), Renal Tubular Dysgenesis of Genetic Origin (p = 6.05x10 -7 ), Lethal Arteriopathy Syndrome due to Fibulin-4 Deficiency (p = 6.54x10 -9 ), EMILIN-1-related Connective Tissue Disease (p = 6.54x10 -9 ), Holt-Oram Syndrome (p = 7.72x10 -10 ), Multisystemic Smooth Muscle Dysfunction Syndrome (p = 9.95x10 -15 ), Distal Hereditary Motor Neuropathy type 2 (p = 4.48x10 -7 ), Congenital Glaucoma (p = 5.24x210 -9 ), Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome (p = 3.77x10 -16 ), Classical-like Ehlers-Danlos Syndrome type 1 (p = 3.77x10 -16 ), Retinoblastoma (p = 1.9x10 -8 ), and Lynch Syndrome (p = 5.04x10 -9 ). 35 novel (21 unique) genes across 12 disorders were identified: ADNP , AOC3 , CDC42EP2 , CHTOP , CNN1 , DES , FOXF1 , FXR1 , HLTF , KCNMB1 , MTF2 , MYH11 , PLN , PNPLA2 , REST , SGCA , SORBS1 , SYNPO2 , TAGLN , WAPL , and ZMYM4 . These genes are proffered as potential biomarkers or therapeutic targets for the corresponding rare diseases discussed.