High Frequency Longitudinal RNAseq Reveals Temporally Varying Genes and Recovery Trajectories in Rats

When living organisms are exposed to potentially toxic chemicals, they respond via changes in gene expression. Traditional differentially expressed gene analysis based on before/after blood samples does not reveal the responses temporal dynamics, and often produces false positives and negatives. Here, we performed longitudinal daily RNA sequencing on rats dosed with tetracycline, isoniazid, carbon tetrachloride, or valproate. We identified 4,302 temporally variable genes (TVGs) with statistically strong change in expression following dosing. Projecting TVG expressions into a 3-dimensional principal component (PC) space reveals consistent trajectories for recovery following dosing, and enables separation of healthy from recovering states with 91% to 99% area under the receiver operator curve. Finally, we observed that Fast Recovery vs. Slow Recovery rats exhibited distinct temporal expression patterns in the TVGs, suggesting that individual variations could be potentially captured via longitudinal RNAseq analysis.