Neural Gene Network Constructor: A Neural Based Model for Reconstructing Gene Regulatory Network

Reconstructing gene regulatory networks (GRNs) and inferring the gene dynamics are important to understand the behavior and the fate of the normal and abnormal cells. Gene regulatory networks could be reconstructed by experimental methods or from gene expression data. Recent advances in Single Cell RNA sequencing technology and the computational method to reconstruct trajectory have generated huge scRNA-seq data tagged with additional time labels. Here, we present a deep learning model “Neural Gene Network Constructor” (NGNC), for inferring gene regulatory network and reconstructing the gene dynamics simultaneously from time series gene expression data. NGNC is a model-free heterogenous model, which can reconstruct any network structure and non-linear dynamics. It consists of two parts: a network generator which incorporating gumbel softmax technique to generate candidate network structure, and a dynamics learner which adopting multiple feedforward neural networks to predict the dynamics. We compare our model with other well-known frameworks on the data set generated by GeneNetWeaver, and achieve the state of the arts results both on network reconstruction and dynamics learning.

[1]  David Z. Chen,et al.  Architecture of the human regulatory network derived from ENCODE data , 2012, Nature.

[2]  Grace X. Y. Zheng,et al.  Massively parallel digital transcriptional profiling of single cells , 2016, Nature Communications.

[3]  Ariel S. Schwartz,et al.  An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man , 2010, Cell.

[4]  Hisanori Kiryu,et al.  SCODE: an efficient regulatory network inference algorithm from single-cell RNA-Seq during differentiation , 2016, bioRxiv.

[5]  Quanquan Gu,et al.  Identifying gene regulatory network rewiring using latent differential graphical models , 2016, Nucleic acids research.

[6]  A. Mortazavi,et al.  Genome-Wide Mapping of in Vivo Protein-DNA Interactions , 2007, Science.

[7]  J. Aerts,et al.  SCENIC: Single-cell regulatory network inference and clustering , 2017, Nature Methods.

[8]  Dario Floreano,et al.  GeneNetWeaver: in silico benchmark generation and performance profiling of network inference methods , 2011, Bioinform..

[9]  Allon M. Klein,et al.  The dynamics of gene expression in vertebrate embryogenesis at single-cell resolution , 2018, Science.

[10]  S. Nadarajah,et al.  The beta Gumbel distribution , 2004 .

[11]  Hannah A. Pliner,et al.  Reversed graph embedding resolves complex single-cell trajectories , 2017, Nature Methods.

[12]  Chris Wiggins,et al.  ARACNE: An Algorithm for the Reconstruction of Gene Regulatory Networks in a Mammalian Cellular Context , 2004, BMC Bioinformatics.

[13]  Jing Liu,et al.  A general deep learning framework for network reconstruction and dynamics learning , 2018, Appl. Netw. Sci..

[14]  Ben Poole,et al.  Categorical Reparameterization with Gumbel-Softmax , 2016, ICLR.