Experimental design and power calculation in omics circadian rhythmicity detection using the cosinor model

Stat Med. 2023 Aug 15;42(18):3236-3258. doi: 10.1002/sim.9803. Epub 2023 Jun 2.

Abstract

Circadian clocks are 24-h endogenous oscillators in physiological and behavioral processes. Though recent transcriptomic studies have been successful in revealing the circadian rhythmicity in gene expression, the power calculation for omics circadian analysis have not been fully explored. In this paper, we develop a statistical method, namely CircaPower, to perform power calculation for circadian pattern detection. Our theoretical framework is determined by three key factors in circadian gene detection: sample size, intrinsic effect size and sampling design. Via simulations, we systematically investigate the impact of these key factors on circadian power calculation. We not only demonstrate that CircaPower is fast and accurate, but also show its underlying cosinor model is robust against variety of violations of model assumptions. In real applications, we demonstrate the performance of CircaPower using mouse pan-tissue data and human post-mortem brain data, and illustrate how to perform circadian power calculation using mouse skeleton muscle RNA-Seq pilot as case study. Our method CircaPower has been implemented in an R package, which is made publicly available on GitHub ( https://github.com/circaPower/circaPower).

Keywords: circadian analysis; cosinor model; experimental design; power calculation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Circadian Rhythm* / genetics
  • Gene Expression Profiling
  • Humans
  • Mice
  • Research Design*
  • Sample Size
  • Transcriptome