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CorrelationCalculator and Filigree: Tools for Data-Driven Network Analysis of Metabolomics Data
Published on: November 10, 2023
Integrated Gene-Metabolite Network Analysis Identifies Pathways Associated with Immune Regulation and Metabolic
Priyanka Banerjee1, Rachel Phillips1, Anna G Holliman1
1Department of Animal Sciences, College of Agriculture, Auburn University, Auburn, AL 36849, USA.
Background/Objectives:
Reproductive inefficiency remains a major contributor to heifer culling and reduced herd longevity in beef systems. This study examined the molecular basis of fertility by analyzing granulosa cells and follicular fluid from Angus-Simmental crossbred heifers classified as fertile or subfertile.
Methods:
Granulosa cells and follicular fluid were collected for RNA sequencing and metabolomic analysis. Differential expression, network, and gene-metabolite integration analyses identified genes, metabolites, and pathways associated with fertility differences between groups.
Results:
We identified 90 differentially expressed genes from the granulosa cells, including CXCL12 and HOXD family members, CALCRL, DNER, GADD45G, immune-related genes, and nine metabolites differentially abundant in follicular fluid, including parabanic acid, pimelic acid, α-tocopherol, glycine, and arachidonic acid. Network analysis revealed extensive rewiring in the network from the subfertile heifers for both genes and metabolites as compared to the fertile heifers. The gene-metabolite integration revealed a high degree of connectivity between arachidonic acid and α-tocopherol, correlating with immune and signaling genes, and between CXCL12 and carbohydrate intermediates. Pathway over-representation analysis highlighted carbohydrate and purine metabolism in fertile heifers, and aminoacyl-tRNA biosynthesis, alanine/aspartate/glutamate metabolism, and Hippo signaling in the subfertile heifers. ABC transporters, ferroptosis, mineral absorption, and glyoxylate/dicarboxylate metabolism were common pathways identified in both groups. Integrative granulosa-follicular fluid analysis revealed coordinated gene-metabolite rewiring in subfertility, including functional candidates (CXCL12, CALCRL, DNER; α-tocopherol, arachidonic acid, fucose, parabanic acid) and fertility-associated pathways.
Conclusions:
These signatures provide novel targets and pathways underlying beef heifer fertility.