Meta-analysis of diurnal transcriptomics in mouse liver reveals low repeatability of rhythm analyses

The accumulation of public transcriptomic timeseries data enables robust meta-analyses that were not possible until recently. To assess the consistency of biological rhythms across studies, 57 public mouse liver tissue timeseries totaling 1096 RNA-seq samples were obtained and analyzed. Only the control groups of each study were included, to create comparable data. Technical factors in RNA-seq library preparation were the largest contributors to transcriptome-level differences, beyond biological or experiment-specific factors such as lighting conditions. Core clock genes were remarkably consistent in phase across all studies. Overlap of genes identified as rhythmic across studies was generally low, with no pair of studies having over 60% overlap. Distributions of phases of significant genes were remarkably inconsistent across studies, but the genes that consistently identified as rhythmic had acrophase clustering near ZT0 and ZT12. Despite the discrepancies between single-study analyses, cross-study analyses found substantial consistency. Running compareRhythms on each pair of studies identified a median of only 11% of the identified rhythmic genes as rhythmic in only one of the two studies. Data was integrated across studies in a JIVE analysis, which showed that the top two components of joint within-study variation are determined by time of day. A shape-invariant model with random effects was fit to the genes to identify the underlying shape of the rhythms, consistent across all studies, including identifying 72 genes with consistently multiple peaks. This dataset accumulates the quantified values from the 1096 samples along with the sample and study meta-data, and the results of JTK and BooteJTK methods run on each of the individual studies. It also includes the spline-fit curves results from the Shape Invarient Models (SIM).Refer to README.txt for file content descriptions. A prior version with fewer studies and analyses is available at https://www.biorxiv.org/content/10.1101/2022.06.22.497209v