Gene regulatory network inference from sparsely sampled noisy data

in Nature Communications (2020), 11

The complexity of biological systems is encoded in gene regulatory networks. Unravelling this intricate web is a fundamental step in understanding the mechanisms of life and eventually developing ... [more ▼]

The complexity of biological systems is encoded in gene regulatory networks. Unravelling this intricate web is a fundamental step in understanding the mechanisms of life and eventually developing efficient therapies to treat and cure diseases. The major obstacle in inferring gene regulatory networks is the lack of data. While time series data are nowadays widely available, they are typically noisy, with low sampling frequency and overall small number of samples. This paper develops a method called BINGO to specifically deal with these issues. Benchmarked with both real and simulated time-series data covering many different gene regulatory networks, BINGO clearly and consistently outperforms state-of-the-art methods. The novelty of BINGO lies in a nonparametric approach featuring statistical sampling of continuous gene expression profiles. BINGO’s superior performance and ease of use, even by non-specialists, make gene regulatory network inference available to any researcher, helping to decipher the complex mechanisms of life. [less ▲]

A multifactorial evaluation framework for gene regulatory network reconstruction

in Foundations of Systems Biology in Engineering (2019)

In the past years, many computational methods have been developed to infer the structure of gene regulatory networks from time series data. However, the applicability and accuracy presumptions of such ... [more ▼]

In the past years, many computational methods have been developed to infer the structure of gene regulatory networks from time series data. However, the applicability and accuracy presumptions of such algorithms remain unclear due to experimental heterogeneity. This paper assesses the performance of recent and successful network inference strategies under a novel, multifactorial evaluation framework in order to highlight pragmatic tradeoffs in experimental design. The effects of data quantity and systems perturbations are addressed, thereby formulating guidelines for efficient resource management. Realistic data were generated from six widely used benchmark models of rhythmic and nonrhythmic gene regulatory systems with random perturbations mimicking the effect of gene knock-out or chemical treatments. Then, time series data of increasing lengths were provided to five state-of-the-art network inference algorithms representing distinctive mathematical paradigms. The performances of such network reconstruction methodologies are uncovered under various experimental conditions. We report that the algorithms do not benefit equally from data increments. Furthermore, at least for the studied rhythmic system, it is more profitable for network inference strategies to be run on long time series rather than short time series with multiple perturbations. By contrast, for the non-rhythmic systems, increasing the number of perturbation experiments yielded better results than increasing the sampling frequency. We expect that future benchmark and algorithm design would integrate such multifactorial considerations to promote their widespread and conscientious usage. [less ▲]

Spatial discretization error in Kalman filtering for discrete-time infinite dimensional systems

in IMA Journal of Mathematical Control and Information (2018), 35(suppl_1), 51-72

We derive a reduced-order state estimator for discrete-time infinite dimensional linear systems with finite dimensional Gaussian input and output noise. This state estimator is the optimal one-step ... [more ▼]

We derive a reduced-order state estimator for discrete-time infinite dimensional linear systems with finite dimensional Gaussian input and output noise. This state estimator is the optimal one-step estimate that takes values in a fixed finite dimensional subspace of the system’s state space — consider, for example, a Finite Element space. The structure of the obtained state estimator is like the Kalman filter, but with an additional optimal embedding operator mapping from the reduced space to the original state space. We derive a Riccati difference equation for the error covariance and use sensitivity analysis to obtain a bound for the error of the state estimate due to the state space discretization. [less ▲]

Bayesian variable selection in linear dynamical systems

E-print/Working paper (2018)

We develop a method for reconstructing regulatory interconnection networks between variables evolving according to a linear dynamical system. The work is motivated by the problem of gene regulatory ... [more ▼]

We develop a method for reconstructing regulatory interconnection networks between variables evolving according to a linear dynamical system. The work is motivated by the problem of gene regulatory network inference, that is, finding causal effects between genes from gene expression time series data. In biological applications, the typical problem is that the sampling frequency is low, and consequentially the system identification problem is ill-posed. The low sampling frequency also makes it impossible to estimate derivatives directly from the data. We take a Bayesian approach to the problem, as it offers a natural way to incorporate prior information to deal with the ill-posedness, through the introduction of sparsity promoting prior for the underlying dynamics matrix. It also provides a framework for modelling both the process and measurement noises. We develop Markov Chain Monte Carlo samplers for the discrete-valued zero-structure of the dynamics matrix, and for the continuous-time trajectory of the system. [less ▲]

Convergence of discrete time Kalman filter estimate to continuous time estimate

in International Journal of Control (2016), 89(4), 668-679

Acoustic wave guides as infinite-dimensional dynamical systems

in ESAIM: Control, Optimisation and Calculus of Variations (2015), 21(2), 324-347

Interaction of vocal fold and vocal tract oscillations

in Proceedings of the 24th Nordic Seminar on Computational Mechanics (2011)

We study the mechanical feedback coupling between the human vocal folds and vocal tract (VT) by simulating fundamental frequency glides over the lowest VT resonance. In the classical source–filter theory ... [more ▼]

We study the mechanical feedback coupling between the human vocal folds and vocal tract (VT) by simulating fundamental frequency glides over the lowest VT resonance. In the classical source–filter theory of speech production, the vocal folds produce a signal which is filtered by the resonator, vocal tract without any feedback. We have developed a computational model of the vocal folds and the VT that also includes a counter pressure from the VT to the vocal folds. This coupling gives rise to new computational observations (such as modal locking) that can be established experimentally. [less ▲]

A LF-pulse from a simple glottal flow model

in Proceedings of the 6th International Workshop on Models and Analysis of Vocal Emissions for Biomedical Applications (2009)