PRIME: Uncovering Circadian Oscillation Patterns and Associations with AD in Untimed Genome-wide Gene Expression across Multiple Brain Regions
This work addresses the challenge of understanding circadian rhythm disruptions in AD for neuroscience and medical research, though it is incremental as it applies a novel method to existing data.
The researchers tackled the problem of uncovering circadian oscillation patterns in untimed genome-wide gene expression data across multiple brain regions and their associations with Alzheimer's disease (AD), revealing that synchronized oscillation patterns were present in 15 pairs of brain regions in controls but disappeared or diminished in AD patients.
The disruption of circadian rhythm is a cardinal symptom for Alzheimer's disease (AD) patients. The full circadian rhythm orchestration of gene expression in the human brain and its inherent associations with AD remain largely unknown. We present a novel comprehensive approach, PRIME, to detect and analyze rhythmic oscillation patterns in untimed high-dimensional gene expression data across multiple datasets. To demonstrate the utility of PRIME, firstly, we validate it by a time course expression dataset from mouse liver as a cross-species and cross-organ validation. Then, we apply it to study oscillation patterns in untimed genome-wide gene expression from 19 human brain regions of controls and AD patients. Our findings reveal clear, synchronized oscillation patterns in 15 pairs of brain regions of control, while these oscillation patterns either disappear or dim for AD. It is worth noting that PRIME discovers the circadian rhythmic patterns without requiring the sample's timestamps. The codes for PRIME, along with codes to reproduce the figures in this paper, are available at https://github.com/xinxingwu-uk/PRIME.