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

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.

Citation
Deng Y, Zenil H, Tegnér J, Kiani NA (2017) HiDi: an efficient reverse engineering schema for large-scale dynamic regulatory network reconstruction using adaptive differentiation. Bioinformatics 33: 3964–3972. Available: http://dx.doi.org/10.1093/bioinformatics/btx501.

Acknowledgements
Vinnova VINNMER fellowship, Stratneuro (to N.A.K.); Swedish Research Council - Vetenskapsra°det (to H.Z.). The founders played no role in the design of the study, in data collection and analysis, in the decision to publish, or in the preparation of the manuscript.

Publisher
Oxford University Press (OUP)

Journal
Bioinformatics

DOI
10.1093/bioinformatics/btx501

arXiv
1706.01241

Additional Links
https://academic.oup.com/bioinformatics/article/doi/10.1093/bioinformatics/btx501/4076057/HiDi-an-efficient-reverse-engineering-schema-for

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