Open Access Research

Phase computations and phase models for discrete molecular oscillators

Onder Suvak* and Alper Demir

Author Affiliations

Department of Electrical and Electronics Engineering, College of Engineering, Koç University Rumeli Feneri Yolu 34450 Sariyer Istanbul, Turkey

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EURASIP Journal on Bioinformatics and Systems Biology 2012, 2012:6 doi:10.1186/1687-4153-2012-6

Published: 11 June 2012

Abstract

Background

Biochemical oscillators perform crucial functions in cells, e.g., they set up circadian clocks. The dynamical behavior of oscillators is best described and analyzed in terms of the scalar quantity, phase. A rigorous and useful definition for phase is based on the so-called isochrons of oscillators. Phase computation techniques for continuous oscillators that are based on isochrons have been used for characterizing the behavior of various types of oscillators under the influence of perturbations such as noise.

Results

In this article, we extend the applicability of these phase computation methods to biochemical oscillators as discrete molecular systems, upon the information obtained from a continuous-state approximation of such oscillators. In particular, we describe techniques for computing the instantaneous phase of discrete, molecular oscillators for stochastic simulation algorithm generated sample paths. We comment on the accuracies and derive certain measures for assessing the feasibilities of the proposed phase computation methods. Phase computation experiments on the sample paths of well-known biological oscillators validate our analyses.

Conclusions

The impact of noise that arises from the discrete and random nature of the mechanisms that make up molecular oscillators can be characterized based on the phase computation techniques proposed in this article. The concept of isochrons is the natural choice upon which the phase notion of oscillators can be founded. The isochron-theoretic phase computation methods that we propose can be applied to discrete molecular oscillators of any dimension, provided that the oscillatory behavior observed in discrete-state does not vanish in a continuous-state approximation. Analysis of the full versatility of phase noise phenomena in molecular oscillators will be possible if a proper phase model theory is developed, without resorting to such approximations.

Keywords:
discrete molecular oscillators; oscillator phase; noise; phase noise; numerical methods; Monte Carlo methods; Stochastic Simulation Algorithm (SSA); isochrons; phase equations; phase computation schemes; phase models