Yue Deng1,2, Hector Zenil1,2, Jesper Tegnér2,3, Narsis A Kiani1,2. 1. Algorithmic Dynamics Lab. 2. Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, Solna and Science for Life Laboratory (SciLifeLab), Karolinska Institute, Stockholm, Sweden. 3. Biological and Environmental Sciences and Engineering Division, Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
Abstract
MOTIVATION: The use of differential equations (ODE) is one of the most promising approaches to network inference. The success of ODE-based approaches has, however, been limited, due to the difficulty in estimating parameters and by their lack of scalability. Here, we introduce a novel method and pipeline to reverse engineer gene regulatory networks from gene expression of time series and perturbation data based upon an improvement on the calculation scheme of the derivatives and a pre-filtration step to reduce the number of possible links. The method introduces a linear differential equation model with adaptive numerical differentiation that is scalable to extremely large regulatory networks. RESULTS: We demonstrate the ability of this method to outperform current state-of-the-art methods applied to experimental and synthetic data using test data from the DREAM4 and DREAM5 challenges. Our method displays greater accuracy and scalability. We benchmark the performance of the pipeline with respect to dataset size and levels of noise. We show that the computation time is linear over various network sizes. AVAILABILITY AND IMPLEMENTATION: The Matlab code of the HiDi implementation is available at: www.complexitycalculator.com/HiDiScript.zip. CONTACT: hzenilc@gmail.com or narsis.kiani@ki.se. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
MOTIVATION: The use of differential equations (ODE) is one of the most promising approaches to network inference. The success of ODE-based approaches has, however, been limited, due to the difficulty in estimating parameters and by their lack of scalability. Here, we introduce a novel method and pipeline to reverse engineer gene regulatory networks from gene expression of time series and perturbation data based upon an improvement on the calculation scheme of the derivatives and a pre-filtration step to reduce the number of possible links. The method introduces a linear differential equation model with adaptive numerical differentiation that is scalable to extremely large regulatory networks. RESULTS: We demonstrate the ability of this method to outperform current state-of-the-art methods applied to experimental and synthetic data using test data from the DREAM4 and DREAM5 challenges. Our method displays greater accuracy and scalability. We benchmark the performance of the pipeline with respect to dataset size and levels of noise. We show that the computation time is linear over various network sizes. AVAILABILITY AND IMPLEMENTATION: The Matlab code of the HiDi implementation is available at: www.complexitycalculator.com/HiDiScript.zip. CONTACT: hzenilc@gmail.com or narsis.kiani@ki.se. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.