Temporal Shifts in Differential Changes and Regulatory Relations among Multi‐Omic Assays in Social Defeat Mouse Model of Post‐Traumatic Stress Disorder
Abstract
We collected hemi‐brain, hippocampus, amygdala, medial prefrontal cortex and ventral striatum from mice exposed to modified social‐stress for 1 to 12 days. We performed transcriptome, DNA‐methylome, miRNAome, and genome‐wide Creb1 transcription binding assays. Temporal and integrative analyses of the multi‐omics datasets were carried out using time‐dependent features extraction, and combinatorial algorithms. Our analyses showed unexpected shifts in relational time coordinates among the different omics datasets. Specifically, for a given gene or probe with significantly changed multi‐omics data points, we observed a temporal shift in its expression changes, methylation of its promoter, modulation of its transcript by upstream miRNAs, and binding of its promoter by transcription regulator. For many significantly changed features, the methylation changes occurred, unexpectedly, at earlier stress days while gene expression changes occurred at later time points. Many of the miRNA changes occurred at eight and later stress days. Our findings showed importance of temporal assays to capture time‐dependent multi‐omics changes as reliable signatures for a given condition. Integrative analyses of multi‐omics measurements based on a single time point may be deficient in many aspects, and may also be misleading if missed observations are interpreted as absence of changes.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2016
- Source ID
- 10.1096/fasebj.30.1_supplement.829.1
Entities
People
- Aarti Gautam
- James L. Meyerhoff
- Marti Jett
- Nabarun Chakraborty
- Rasha Hammamieh
- Seid Muhie
Organizations
- United States Army Medical Research and Development Command