Motivation The circadian rhythm drives the oscillatory expression of thousands of genes across all tissues. The recent revolution in high-throughput transcriptomics, coupled with the significant implications of the circadian clock for human health, has sparked an interest in circadian profiling studies to discover genes under circadian control.
Result We present TimeCycle: a topology-based rhythm detection method designed to identify cycling transcripts. For a given time-series, the method reconstructs the state space using time-delay embedding, a data transformation technique from dynamical systems theory. In the embedded space, Takens’ theorem proves that the dynamics of a rhythmic signal will exhibit circular patterns. The degree of circularity of the embedding is calculated as a persistence score using persistent homology, an algebraic method for discerning the topological features of data. By comparing the persistence scores to a bootstrapped null distribution, cycling genes are identified. Results in both synthetic and biological data highlight Time-Cycle’s ability to identify cycling genes across a range of sampling schemes, number of replicates, and missing data. Comparison to competing methods highlights their relative strengths, providing guidance as to the optimal choice of cycling detection method.
Availability and Implementation A fully documented open-source R package implementing Time-Cycle is available at: https://nesscoder.github.io/TimeCycle/.
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TimeTrial: An Interactive Application for Optimizing the Design and Analysis of Transcriptomic Time-Series Data in Circadian Biology Research
The circadian rhythm drives the oscillatory expression of thousands of genes across all tissues, coordinating physiological processes. The effect of this rhythm on health has generated increasing interest in discovering genes under circadian control by searching for periodic patterns in transcriptomic time-series experiments. While algorithms for detecting cycling transcripts have advanced, there remains little guidance quantifying the effect of experimental design and analysis choices on cycling detection accuracy. We present TimeTrial, a user-friendly benchmarking framework using both real and synthetic data to investigate cycle detection algorithms’ performance and improve circadian experimental design. Results show that the optimal choice of analysis method depends on the sampling scheme, noise level, and shape of the waveform of interest and provides guidance on the impact of sampling frequency and duration on cycling detection accuracy. The TimeTrial software is freely available for download and may also be accessed through a web interface. By supplying a tool to vary and optimize experimental design considerations, TimeTrial will enhance circadian transcriptomics studies.
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- Award ID(s):
- 1764421
- NSF-PAR ID:
- 10251810
- Date Published:
- Journal Name:
- Journal of Biological Rhythms
- Volume:
- 35
- Issue:
- 5
- ISSN:
- 0748-7304
- Page Range / eLocation ID:
- 439 to 451
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1177/0748730420934672
