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The disruption of circadian rhythm is a cardinal symptom for Alzheimer'sdisease (AD) patients. The full circadian rhythm orchestration of geneexpression in the human brain and its inherent associations with AD remainlargely unknown. We present a novel comprehensive approach, PRIME, to detectand analyze rhythmic oscillation patterns in untimed high-dimensional geneexpression data across multiple datasets. To demonstrate the utility of PRIME,firstly, we validate it by a time course expression dataset from mouse liver asa cross-species and cross-organ validation. Then, we apply it to studyoscillation patterns in untimed genome-wide gene expression from 19 human brainregions of controls and AD patients. Our findings reveal clear, synchronizedoscillation patterns in 15 pairs of brain regions of control, while theseoscillation patterns either disappear or dim for AD. It is worth noting thatPRIME discovers the circadian rhythmic patterns without requiring the sample'stimestamps. The codes for PRIME, along with codes to reproduce the figures inthis paper, are available at https://github.com/xinxingwu-uk/PRIME.

PRIME: Uncovering Circadian Oscillation Patterns and Associations with AD in Untimed Genome-wide Gene Expression across Multiple Brain Regions