1-CMDb: A Curated Database of Genomic Variations of the One-Carbon Metabolism Pathway

Abstract

Background: The one-carbon metabolism pathway is vital in maintaining tissue homeostasis by driving the critical reactions of folate and methionine cycles. A myriad of genetic and epigenetic events mark the rate of reactions in a tissue-specific manner. Integration of these to predict and provide personalized health management requires robust computational tools that can process multiomics data. The DNA sequences that may determine the chain of biological events and the endpoint reactions within one-carbon metabolism genes remain to be comprehensively recorded. Hence, we designed the one-carbon metabolism database (1-CMDb) as a platform to interrogate its association with a host of human disorders. Methods: DNA sequence and network information of a total of 48 genes were extracted from a literature survey and KEGG pathway that are involved in the one-carbon folate-mediated pathway. The information generated, collected, and compiled for all these genes from the UCSC genome browser included the single nucleotide polymorphisms (SNPs), CpGs, copy number variations (CNVs), and miRNAs, and a comprehensive database was created. Furthermore, a significant correlation analysis was performed for SNPs in the pathway genes. Results: Detailed data of SNPs, CNVs, CpG islands, and miRNAs for 48 folate pathway genes were compiled. The SNPs in CNVs (9670), CpGs (984), and miRNAs (14) were also compiled for all pathway genes. The SIFT score, the prediction and PolyPhen score, as well as the prediction for each of the SNPs were tabulated and represented for folate pathway genes. Also included in the database for folate pathway genes were the links to 124 various phenotypes and disease associations as reported in the literature and from publicly available information. Conclusion: A comprehensive database was generated consisting of genomic elements within and among SNPs, CNVs, CpGs, and miRNAs of one-carbon metabolism pathways to facilitate (a) single source of information and (b) integration into large-genome scale network analysis to be developed in the future by the scientific community. The database can be accessed at http://slsdb.manipal.edu/ocm/.

One-Carbon Metabolism Links Nutrition Intake to Embryonic Development via Epigenetic Mechanisms

“…Using DNA sequencing and by establishing gene network, a total of 48 genes involved in the folate-related OCM pathway were extracted from the KEGG pathway and literature survey. Using this information, a complex database was generated including CpGs, miRNAs, copy number variations (CNVs), and single-nucleotide polymorphisms (SNPs) underlying the OCM pathways (http://slsdb.manipal.edu/ocm/) [83]. Based on these data, recent studies have focused on the potential mechanism between OCM and miRNAs.…”