Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Antoulas, Athanasios C., Zhu, Bokai, Zhang, Qiang, York, Brian, O’Malley, Bert W., Dacso, Clifford C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145530/
https://www.ncbi.nlm.nih.gov/pubmed/30231032
http://dx.doi.org/10.1371/journal.pone.0198503
_version_ 1783356273236901888
author Antoulas, Athanasios C.
Zhu, Bokai
Zhang, Qiang
York, Brian
O’Malley, Bert W.
Dacso, Clifford C.
author_facet Antoulas, Athanasios C.
Zhu, Bokai
Zhang, Qiang
York, Brian
O’Malley, Bert W.
Dacso, Clifford C.
author_sort Antoulas, Athanasios C.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6145530
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-61455302018-09-27 A novel mathematical method for disclosing oscillations in gene transcription: A comparative study Antoulas, Athanasios C. Zhu, Bokai Zhang, Qiang York, Brian O’Malley, Bert W. Dacso, Clifford C. PLoS One Research Article 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. Public Library of Science 2018-09-19 /pmc/articles/PMC6145530/ /pubmed/30231032 http://dx.doi.org/10.1371/journal.pone.0198503 Text en © 2018 Antoulas et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Antoulas, Athanasios C.
Zhu, Bokai
Zhang, Qiang
York, Brian
O’Malley, Bert W.
Dacso, Clifford C.
A novel mathematical method for disclosing oscillations in gene transcription: A comparative study
title A novel mathematical method for disclosing oscillations in gene transcription: A comparative study
title_full A novel mathematical method for disclosing oscillations in gene transcription: A comparative study
title_fullStr A novel mathematical method for disclosing oscillations in gene transcription: A comparative study
title_full_unstemmed A novel mathematical method for disclosing oscillations in gene transcription: A comparative study
title_short A novel mathematical method for disclosing oscillations in gene transcription: A comparative study
title_sort novel mathematical method for disclosing oscillations in gene transcription: a comparative study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145530/
https://www.ncbi.nlm.nih.gov/pubmed/30231032
http://dx.doi.org/10.1371/journal.pone.0198503
work_keys_str_mv AT antoulasathanasiosc anovelmathematicalmethodfordisclosingoscillationsingenetranscriptionacomparativestudy
AT zhubokai anovelmathematicalmethodfordisclosingoscillationsingenetranscriptionacomparativestudy
AT zhangqiang anovelmathematicalmethodfordisclosingoscillationsingenetranscriptionacomparativestudy
AT yorkbrian anovelmathematicalmethodfordisclosingoscillationsingenetranscriptionacomparativestudy
AT omalleybertw anovelmathematicalmethodfordisclosingoscillationsingenetranscriptionacomparativestudy
AT dacsocliffordc anovelmathematicalmethodfordisclosingoscillationsingenetranscriptionacomparativestudy
AT antoulasathanasiosc novelmathematicalmethodfordisclosingoscillationsingenetranscriptionacomparativestudy
AT zhubokai novelmathematicalmethodfordisclosingoscillationsingenetranscriptionacomparativestudy
AT zhangqiang novelmathematicalmethodfordisclosingoscillationsingenetranscriptionacomparativestudy
AT yorkbrian novelmathematicalmethodfordisclosingoscillationsingenetranscriptionacomparativestudy
AT omalleybertw novelmathematicalmethodfordisclosingoscillationsingenetranscriptionacomparativestudy
AT dacsocliffordc novelmathematicalmethodfordisclosingoscillationsingenetranscriptionacomparativestudy