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Comparative Study
. 2018 Sep 19;13(9):e0198503.
doi: 10.1371/journal.pone.0198503. eCollection 2018.

A novel mathematical method for disclosing oscillations in gene transcription: A comparative study

Athanasios C Antoulas  1   2   3 , Bokai Zhu  3 , Qiang Zhang  1 , Brian York  3   4 , Bert W O'Malley  3   4 , Clifford C Dacso  1   3   4
Affiliations
Comparative Study

A novel mathematical method for disclosing oscillations in gene transcription: A comparative study

Athanasios C Antoulas et al. PLoS One. .

Abstract

Circadian rhythmicity, the 24-hour cycle responsive to light and dark, is determined by periodic oscillations in gene transcription. This phenomenon has broad ramifications in physiologic function. Recent work has disclosed more cycles in gene transcription, and to the uncovering of these we apply a novel signal processing methodology known as the pencil method and compare it to conventional parametric, nonparametric, and statistical methods.

Methods: In order to assess periodicity of gene expression over time, we analyzed a database derived from livers of mice entrained to a 12-hour light/12-hour dark cycle. We also analyzed artificially generated signals to identify differences between the pencil decomposition and other alternative methods.

Results: The pencil decomposition revealed hitherto-unsuspected oscillations in gene transcription with 12-hour periodicity. The pencil method was robust in detecting the 24-hour circadian cycle that was known to exist, as well as confirming the existence of shorter-period oscillations. A key consequence of this approach is that orthogonality of the different oscillatory components can be demonstrated. thus indicating a biological independence of these oscillations, that has been subsequently confirmed empirically by knocking out the gene responsible for the 24-hour clock.

Conclusion: System identification techniques can be applied to biological systems and can uncover important characteristics that may elude visual inspection of the data.

Significance: The pencil method provides new insights on the essence of gene expression and discloses a wide variety of oscillations in addition to the well-studied circadian pattern. This insight opens the door to the study of novel mechanisms by which oscillatory gene expression signals exert their regulatory effect on cells to influence human diseases.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Curves for simulation data.
Fig 2
Fig 2. Heat maps of the wavelet transform.
Fig 3
Fig 3. Curves for simulation data.
Fig 4
Fig 4. Heat maps (left) and fit curves (right).
Fig 5
Fig 5. Plots for averaged data.
Fig 6
Fig 6. Plots for mouse #1.
Fig 7
Fig 7. Ambulatory activity: Approximation and oscillations.
Fig 8
Fig 8. Comparison between pencil and LS poles.
Fig 9
Fig 9. Results of analysis of 18484 genes using various methods.
See this image and copyright information in PMC

References

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