Abstract: TH-PO631
Examining Transcriptional Coordination Among Pathways Using Single Cell Transcriptomics
Session Information
- Health Maintenance, Nutrition, Metabolism - I
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1300 Health Maintenance, Nutrition, and Metabolism
Author
- Agarwal, Divyansh, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Background
Recent evidence suggests that the intracellular activity of certain immune pathways, such as the complement, engages in novel cross-talk with metabolic pathways. This pathway-pathway interaction is critical in directing a catered cellular response. Single cell RNA sequencing (scRNA-seq) provides an unprecedented opportunity to understand whether certain biological pathways act in synchrony.
Methods
Using single cell transcriptomics data from five different T cell subtypes (CD4+ naïve, memory, helper and regulatory T cells, and CD8+ cytotoxic T cells), we developed a model for assessing the canonical correlation between two pathways. We examined the significance of the correlation using a modified permutation null distribution that accounts for technical covariates. Complement dysregulation is a hallmark of several kidney diseases, so we used the complement as a bait immune pathway to detect which metabolic pathways it is correlated with, and how that correlation differs across T cell subtypes.
Results
Using canonical correlation analysis, we detect pairwise coordination among biological pathways, and explore how the complement pathway might interact with various metabolic pathways in different T cell subtypes. We found that complement-metabolism crosstalk varies substantially by T cell subtype. For instance, while the complement pathway demonstrated a significant canonical correlation with the arachidonic acid and NAD metabolism pathways in CD4+ memory T cells, we did not find evidence for the same in CD4+ naïve T cells. Further, in the latter naïve T cell type, glycolysis and the pentose phosphate pathways showed evidence for transcriptional coordination with complement.
Conclusion
Our method is a widely applicable approach that can be used to assess the differences in pathway cross-talk between cell-types, as well between a healthy and disease state.
Examining the complement-metabolic axis using single cell RNA sequencing
Funding
- Private Foundation Support