Dynamical differential expression (DyDE) reveals the period control mechanisms of the Arabidopsis circadian oscillator

in PLoS Computational Biology (2019)

The circadian oscillator, an internal time-keeping device found in most organisms, enables timely regulation of daily biological activities by maintaining synchrony with the external environment. The ... [more ▼]

The circadian oscillator, an internal time-keeping device found in most organisms, enables timely regulation of daily biological activities by maintaining synchrony with the external environment. The mechanistic basis underlying the adjustment of circadian rhythms to changing external conditions, however, has yet to be clearly elucidated. We explored the mechanism of action of nicotinamide in Arabidopsis thaliana, a metabolite that lengthens the period of circadian rhythms, to understand the regulation of circadian period. To identify the key mechanisms involved in the circadian response to nicotinamide, we developed a systematic and practical modeling framework based on the identification and comparison of gene regulatory dynamics. Our mathematical predictions, confirmed by experimentation, identified key transcriptional regulatory mechanisms of circadian period and uncovered the role of blue light in the response of the circadian oscillator to nicotinamide. We suggest that our methodology could be adapted to predict mechanisms of drug action in complex biological systems. [less ▲]

Network Reconstruction from Intrinsic Noise

in The proceedings of the American Control Conference (2014)

This paper considers the problem of inferring the structure and dynamics of an unknown network driven by unknown noise inputs. Equivalently we seek to identify direct causal dependencies among manifest ... [more ▼]

This paper considers the problem of inferring the structure and dynamics of an unknown network driven by unknown noise inputs. Equivalently we seek to identify direct causal dependencies among manifest variables only from observations of these variables. We consider linear, time-invariant systems of minimal order and with one noise source per measured state. If the transfer matrix from the inputs to manifest states is known to be minimum phase, this problem is shown to have a unique solution irrespective of the network topology. This is equivalent to there being only one spectral factor (up to a choice of signs of the inputs) of the output spectral density that satisfies these assumptions. Hence for this significant class of systems, the network reconstruction problem is well posed. [less ▲]

Robust Signal-Structure Reconstruction

in The proceedings of the IEEE 52nd Annual Conference on Decision and Control (2013)

This paper focuses on the reconstruction of the signal structure of a system in the presence of noise and nonlinearities. Previous results on polynomial time reconstruction in this area were restricted to ... [more ▼]

This paper focuses on the reconstruction of the signal structure of a system in the presence of noise and nonlinearities. Previous results on polynomial time reconstruction in this area were restricted to systems where target specificity was part of the inherent structure, [5]. This work extends these results to all reconstructible systems and proposes a faster reconstruction algorithm along with an improved model selection procedure. Finally, a simulation study then details the performance of this new algorithm on reconstructible systems. [less ▲]