RT Journal Article
SR Electronic
T1 A novel mathematical method for disclosing oscillations in gene transcription: a comparative study
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 151720
DO 10.1101/151720
A1 Athanasios C. Antoulas
A1 Bokai Zhu
A1 Qiang Zhang
A1 Brian York
A1 Bert W. O’Malley
A1 Clifford C. Dacso
YR 2017
UL http://biorxiv.org/content/early/2017/06/21/151720.abstract
AB Circadian rhythmicity, the 24-hour cycle responsive to light and dark, is contributed to 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. 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 similar methods. Results: The pencil decomposition revealed hitherto unsuspected oscillations in gene transcription with 12 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, This indicates a biological independence of these oscillations, which 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.