Dataset Information

Inferring causality in biological oscillators.

ABSTRACT: Fundamental to biological study is identifying regulatory interactions. The recent surge in time-series data collection in biology provides a unique opportunity to infer regulations computationally. However, when components oscillate, model-free inference methods, while easily implemented, struggle to distinguish periodic synchrony and causality. Alternatively, model-based methods test the reproducibility of time series given a specific model but require inefficient simulations and have limited applicability. We develop an inference method based on a general model of molecular, neuronal, and ecological oscillatory systems that merges the advantages of both model-based and model-free methods, namely accuracy, broad applicability, and usability. Our method successfully infers the positive and negative regulations within various oscillatory networks, e.g., the repressilator and a network of cofactors at the pS2 promoter, outperforming popular inference methods. We provide a computational package, ION (Inferring Oscillatory Networks), that users can easily apply to noisy, oscillatory time series to uncover the mechanisms by which diverse systems generate oscillations. Accompanying MATLAB code under a BSD-style license and examples are available at ttps://github.com/Mathbiomed/ION. Additionally, the code is available under a CC-BY 4.0 License at https://doi.org/10.6084/m9.figshare.16431408.v1. Supplementary data are available at Bioinformatics online.

SUBMITTER: Tyler J

PROVIDER: S-EPMC8696107 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Inferring causality in biological oscillators.

Tyler Jonathan J Forger Daniel D Kim Jae Kyoung JK

Bioinformatics (Oxford, England) 20211201 1

<h4>Motivation</h4>Fundamental to biological study is identifying regulatory interactions. The recent surge in time-series data collection in biology provides a unique opportunity to infer regulations computationally. However, when components oscillate, model-free inference methods, while easily implemented, struggle to distinguish periodic synchrony and causality. Alternatively, model-based methods test the reproducibility of time series given a specific model but require inefficient simulation ...[more]

PMID: 34463706

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Project description:One of the most challenging problems in the study of complex dynamical systems is to find the statistical interdependencies among the system components. Granger causality (GC) represents one of the most employed approaches, based on modeling the system dynamics with a linear vector autoregressive (VAR) model and on evaluating the information flow between two processes in terms of prediction error variances. In its most advanced setting, GC analysis is performed through a state-space (SS) representation of the VAR model that allows to compute both conditional and unconditional forms of GC by solving only one regression problem. While this problem is typically solved through Ordinary Least Square (OLS) estimation, a viable alternative is to use Artificial Neural Networks (ANNs) implemented in a simple structure with one input and one output layer and trained in a way such that the weights matrix corresponds to the matrix of VAR parameters. In this work, we introduce an ANN combined with SS models for the computation of GC. The ANN is trained through the Stochastic Gradient Descent L1 (SGD-L1) algorithm, and a cumulative penalty inspired from penalized regression is applied to the network weights to encourage sparsity. Simulating networks of coupled Gaussian systems, we show how the combination of ANNs and SGD-L1 allows to mitigate the strong reduction in accuracy of OLS identification in settings of low ratio between number of time series points and of VAR parameters. We also report how the performances in GC estimation are influenced by the number of iterations of gradient descent and by the learning rate used for training the ANN. We recommend using some specific combinations for these parameters to optimize the performance of GC estimation. Then, the performances of ANN and OLS are compared in terms of GC magnitude and statistical significance to highlight the potential of the new approach to reconstruct causal coupling strength and network topology even in challenging conditions of data paucity. The results highlight the importance of of a proper selection of regularization parameter which determines the degree of sparsity in the estimated network. Furthermore, we apply the two approaches to real data scenarios, to study the physiological network of brain and peripheral interactions in humans under different conditions of rest and mental stress, and the effects of the newly emerged concept of remote synchronization on the information exchanged in a ring of electronic oscillators. The results highlight how ANNs provide a mesoscopic description of the information exchanged in networks of multiple interacting physiological systems, preserving the most active causal interactions between cardiovascular, respiratory and brain systems. Moreover, ANNs can reconstruct the flow of directed information in a ring of oscillators whose statistical properties can be related to those of physiological networks.

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Inferring causality in biological oscillators.

Publications

Inferring causality in biological oscillators.

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