Bioinformatics and In-Silico Findings Reveal Candidate Genes forTetralogy of Fallot via Integrative Multi-Omics DataOA
Background:Tetralogy of Fallot(TOF),the predominant cyanotic congenital heart defect,arisesfrom multifactorial gene-envirorment interactions disrup ting cardiac developmental networks.This studyinvestiga ted TOF-specific transcriptional alterations and identified high-confidence candidate genes.Methods:Based on GSE36761 transcriptome data,a weighted gene co-exp ression network analysis(WGCNA)andprotein-protein interaction(PPI)network were conducted to identify TOF-related sub-netrwork and Hub genes.The potentialbiological functions among these genes were revealed by enrichment analysis.Genetic,epigeneticand transcriptional alteration in the Fub genes were analyzed with leveraged public resources:a methylationdataset(CSE62629)and two single-cell datasets(EGAS00001003996 and GSE126128),Results:Eight Hub geneswere identified using the WGCNA network and PPl network,and functional errichment analysis revealedthatGJA1,RUNX2,FTK7,PRICKLE1,and SPRP1 were involved in the morphogenesis of an epithelium,anddysregulation of the signaling were also found in the other two TOF datasets,Furthermore,the study foundthat the promoters of GJA1,RUNX2,FTK7,and PRICKLE1 genes were hypermethylated and that GJA1 andSFRP1 are highly expressed in mouse second heart field cells and neural crest cells,and the la tter is expressedin human embry onic outflow tract cells.Since RUNX2 was not expressed in human and mouse embryonichearts,GJA1,FTK7,PRICKLE1,and SPRP1 were ultimately identified as TOF candidate genes.Conclusion:Based on the WGCNA network and various bioinformatics analysis approaches,we screened 4 TOF candidatepathogenic genes,and found that the signaling pathways related to the morphogenesis of an epithelium maybe involved in the pathogenesis of TOF.
Jiawei Shi;Zhen Wang;Ying Bai;shiying Li;Xin Zhang;Tianshu Liu;Liu Hong;Li Cui;Yi Zhang;Jing Ma;Juanjuan Liu;Jing Zhang;Haiyan Cao;Jing Wan
Department of Utrasound Medicine,Union Hosp ital,Tongji Medic al College,Huazhong University of Sciance andTechnology,Wuhan,430022,China Clinical Reseatch Center for Medical lmaging in Hubei Province,Huazhong University of Sciance and Technolog,wuhan,430022,China Hubei Province Key Laboratory ofMoleculat Imaging,Huazhong Uriversity of Science and Technology,Wuhan,430022,ChinaDepartment of Utrasound Medicine,Union Hosp ital,Tongji Medic al College,Huazhong University of Sciance andTechnology,Wuhan,430022,China Clinical Reseatch Center for Medical lmaging in Hubei Province,Huazhong University of Sciance and Technolog,wuhan,430022,China Hubei Province Key Laboratory ofMoleculat Imaging,Huazhong Uriversity of Science and Technology,Wuhan,430022,ChinaDepartment of Utrasound Medicine,Union Hosp ital,Tongji Medic al College,Huazhong University of Sciance andTechnology,Wuhan,430022,China Clinical Reseatch Center for Medical lmaging in Hubei Province,Huazhong University of Sciance and Technolog,wuhan,430022,China Hubei Province Key Laboratory ofMoleculat Imaging,Huazhong Uriversity of Science and Technology,Wuhan,430022,ChinaDepartment of Utrasound Medicine,Union Hosp ital,Tongji Medic al College,Huazhong University of Sciance andTechnology,Wuhan,430022,China Clinical Reseatch Center for Medical lmaging in Hubei Province,Huazhong University of Sciance and Technolog,wuhan,430022,China Hubei Province Key Laboratory ofMoleculat Imaging,Huazhong Uriversity of Science and Technology,Wuhan,430022,ChinaDepartment of Utrasound Medicine,Union Hosp ital,Tongji Medic al College,Huazhong University of Sciance andTechnology,Wuhan,430022,China Clinical Reseatch Center for Medical lmaging in Hubei Province,Huazhong University of Sciance and Technolog,wuhan,430022,China Hubei Province Key Laboratory ofMoleculat Imaging,Huazhong Uriversity of Science and Technology,Wuhan,430022,ChinaDepartment of Utrasound Medicine,Union Hosp ital,Tongji Medic al College,Huazhong University of Sciance andTechnology,Wuhan,430022,China Clinical Reseatch Center for Medical lmaging in Hubei Province,Huazhong University of Sciance and Technolog,wuhan,430022,China Hubei Province Key Laboratory ofMoleculat Imaging,Huazhong Uriversity of Science and Technology,Wuhan,430022,ChinaDepartment of Utrasound Medicine,Union Hosp ital,Tongji Medic al College,Huazhong University of Sciance andTechnology,Wuhan,430022,China Clinical Reseatch Center for Medical lmaging in Hubei Province,Huazhong University of Sciance and Technolog,wuhan,430022,China Hubei Province Key Laboratory ofMoleculat Imaging,Huazhong Uriversity of Science and Technology,Wuhan,430022,ChinaDepartment of Utrasound Medicine,Union Hosp ital,Tongji Medic al College,Huazhong University of Sciance andTechnology,Wuhan,430022,China Clinical Reseatch Center for Medical lmaging in Hubei Province,Huazhong University of Sciance and Technolog,wuhan,430022,China Hubei Province Key Laboratory ofMoleculat Imaging,Huazhong Uriversity of Science and Technology,Wuhan,430022,ChinaDepartment of Utrasound Medicine,Union Hosp ital,Tongji Medic al College,Huazhong University of Sciance andTechnology,Wuhan,430022,China Clinical Reseatch Center for Medical lmaging in Hubei Province,Huazhong University of Sciance and Technolog,wuhan,430022,China Hubei Province Key Laboratory ofMoleculat Imaging,Huazhong Uriversity of Science and Technology,Wuhan,430022,ChinaDepartment of Utrasound Medicine,Union Hosp ital,Tongji Medic al College,Huazhong University of Sciance andTechnology,Wuhan,430022,China Clinical Reseatch Center for Medical lmaging in Hubei Province,Huazhong University of Sciance and Technolog,wuhan,430022,China Hubei Province Key Laboratory ofMoleculat Imaging,Huazhong Uriversity of Science and Technology,Wuhan,430022,ChinaDepartment of Utrasound Medicine,Union Hosp ital,Tongji Medic al College,Huazhong University of Sciance andTechnology,Wuhan,430022,China Clinical Reseatch Center for Medical lmaging in Hubei Province,Huazhong University of Sciance and Technolog,wuhan,430022,China Hubei Province Key Laboratory ofMoleculat Imaging,Huazhong Uriversity of Science and Technology,Wuhan,430022,ChinaDepartment of Utrasound Medicine,Union Hosp ital,Tongji Medic al College,Huazhong University of Sciance andTechnology,Wuhan,430022,China Clinical Reseatch Center for Medical lmaging in Hubei Province,Huazhong University of Sciance and Technolog,wuhan,430022,China Hubei Province Key Laboratory ofMoleculat Imaging,Huazhong Uriversity of Science and Technology,Wuhan,430022,ChinaDepartment of Utrasound Medicine,Union Hosp ital,Tongji Medic al College,Huazhong University of Sciance andTechnology,Wuhan,430022,China Clinical Reseatch Center for Medical lmaging in Hubei Province,Huazhong University of Sciance and Technolog,wuhan,430022,China Hubei Province Key Laboratory ofMoleculat Imaging,Huazhong Uriversity of Science and Technology,Wuhan,430022,ChinaDepartment of Utrasound Medicine,Union Hosp ital,Tongji Medic al College,Huazhong University of Sciance andTechnology,Wuhan,430022,China Clinical Reseatch Center for Medical lmaging in Hubei Province,Huazhong University of Sciance and Technolog,wuhan,430022,China Hubei Province Key Laboratory ofMoleculat Imaging,Huazhong Uriversity of Science and Technology,Wuhan,430022,China
医药卫生
Tetralogy of Fallotgene regulatory networksweighted gene co-expression network analysisprotein-protein interaction networkd isease candidate genes
《Congenital Heart Disease》 2025 (2)
P.213-229,17
supported by the National Natural Science Found ation of China(No.8230045i for Zhen Wang,82302230 for jiawei Shi,82202194 for Jing Wang and 82171961 for Haiyan Cao).
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