Design Principles and Analysis Guidelines for Understanding Time-of-Day Effects in the Brain

Abstract

Circadian omics analysis is powerful to understand how daily rhythms regulate physiology and how these rhythms are altered under disease conditions. Circadian disruption is known to cause several neurological disorders such as irregular sleep patterns, anxiety, depression, and neurodegeneration. On the other hand, several neurodegenerative diseases such as Parkinson’s, Huntington’s, and Alzheimer’s disease are associated with a loss of daily rhythms. Despite this, very few studies have investigated circadian rhythms of gene expression in different regions of the healthy brain and even fewer under disease conditions. However, with the increasing availability and cost-effectiveness of omics technologies and also the development of single-cell and spatial omics technologies, we expect a huge boom in such studies in the future. It will be essential that these future studies follow definite principles and guidelines for tissue sampling and data generation and analysis. This will ensure rigor in designing and performing experiments, ensure reproducibility, and also facilitate comparisons with existing and future datasets. This chapter outlines key principles and guidelines for experimental design, omics data generation, and rhythmicity analysis, with a specific focus on circadian transcriptomics in mammalian brain.