HiDi: an efficient reverse engineering schema for large-scale dynamic regulatory network reconstruction using adaptive differentiation.

Deng Y, Zenil H, Tegnér J, Kiani NA

Bioinformatics 33 (24) 3964-3972 [2017-12-15; online 2017-09-30]

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. 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. The Matlab code of the HiDi implementation is available at: www.complexitycalculator.com/HiDiScript.zip. hzenilc@gmail.com or narsis.kiani@ki.se. Supplementary data are available at Bioinformatics online.

Affiliated researcher

PubMed 28961895

DOI 10.1093/bioinformatics/btx501

Crossref 10.1093/bioinformatics/btx501

pii: 4076057

Publications 9.5.0