How to Identify Differentially Associated Genes for Differential Metabolites?
After identifying differential metabolites, the following approaches can be used to search for genes associated with them:
Database and Literature Search
Search for genes and biological pathways related to the metabolites by using their names or structures in literature databases (such as PubMed) and specialized metabolomics databases (such as HMDB, KEGG, MetaboAnalyst).
Bioinformatics Tools
1. MetaboAnalyst
Input differential metabolite data to perform pathway enrichment analysis, identifying associated metabolic pathways and genes.
2. Ingenuity Pathway Analysis (IPA)
Integrates metabolite, gene, and protein data to provide pathway analysis and gene association insights.
Gene Expression Data Integration
If gene expression data (e.g., RNA-seq) is available, perform integrated analysis:
1. Use bioinformatics tools in R (such as DESeq2, EdgeR) to analyze gene expression data and identify differentially expressed genes.
2. Correlate these genes with differential metabolite data to uncover common enriched pathways or regulatory networks.
Multi-Omics Data Integration
Use multi-omics data integration tools like OmicsNet or Cytoscape to combine metabolomic, transcriptomic, and proteomic data for network analysis, identifying key regulatory genes and pathways.
Experimental Validation
Validate the role of candidate genes on metabolite levels using experimental techniques (such as gene knockout or overexpression) to confirm their causal relationships.
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