Gene Regulatory Network Generator in Julia (JuGRN)

Introduction

JuGRN is a code generation system that transforms simple descriptions of the connectivity of gene regulatory networks into model code written in the Julia programming language. JuGRN has been used in the publications:

1. Tasseff R, Jensen H, Congleton J, Dai W, Rogers K, Sagar A, Yen A and J. Varner (2017) An Effective Model of the Retinoic Acid Induced Differentiation Program, Sci Reports, 7:14327 doi:10.1038/s41598-017-14523-5
2. Gould R, Bassen DM, Chakrabarti A, Varner JD and Butcher J (2016) Population Heterogeneity in the Epithelial to Mesenchymal Transition Is Controlled by NFAT and Phosphorylated Sp1. PLoS Comput Biol 12(12): e1005251. doi:10.1371/journal.pcbi.1005251

to generate gene regulatory network code.

Installation and Requirements

JuGRN.jl is organized as a Julia package which can be installed in the package mode of Julia.

Start of the Julia REPL and enter the package mode using the ] key (to get back press the backspace or ^C keys). Then, at the prompt enter:

(v1.1) pkg> add https://github.com/varnerlab/JuGRN-Generator.git

This will install the JuGRN.jl package and the other required packages. JuGRN.jl requires Julia 1.3.x and above.

JuGRN.jl is open source. You can download this repository as a zip file, or clone or pull it by using the command (from the command-line):

$ git pull https://github.com/varnerlab/JuGRN-Generator.git

or

$ git clone https://github.com/varnerlab/JuGRN-Generator.git

How do I generate model code?

To generate a GRN model, issue the command make_julia_model.jl from the command line (outside of the REPL):

$ julia make_julia_model.jl -m <input path> -o <output path> -s <host type>

The make_julia_model.jl command takes four command line arguments:

Argument	Required	Default	Description
-m	Yes	none	Path to model input file (your *.net file)
-o	No	current directory	Path where files are written
-s	No	bacterial	Host type (bacterial | mammalian)

Format for the GRN model input file

JuGRN-Generator transforms structured flat files into GRN model code. JuGRN-Generator takes flat files of the form:

// ----------------------------------------------------------------------- //
// JuGRN interactions -
//
// Record:
// actor {activate(*),induce(*) | inhibit(*),repress(*)} (target,...)
// ---------------------------------------------------------------------- //

// three gene memory network -
gene_1 induces (gene_2,gene_3)
gene_2 activates gene_3
gene_3 activates gene_2

The model specification file (by default given the filename Network.net) defines the biology of the model that gets generated. JuGRN generates the files:

Filename	Description
AdjDriver.jl	Driver function to solve the adjoint system of equations (sensitivity analysis)
Balances.jl	Material balance equations for genes, mRNA and proteins in the GRN
Control.jl	Encodes the control logic described in your GRN network file
DataDictionary.jl	Encodes the model parameters e.g., initial conditions or promoter function parameters in a Julia dictionary
Degradation.dat	Stoichiometric matrix for mRNA and protein degradation reactions
Dilution.dat	Stoichiometric matrix for mRNA and protein dilution reactions
Discrete.jl	Contains methods to evaluate the discrete mass balance equations (discretized using a zero-order-hold)
Driver.jl	Example script that can be used to solve the continuous material balance equations
Include.jl	Includes all the JuGRN files into the current workspace
Kinetics.jl	Encodes the rate of transcription, translation and degradation for mRNA and protein species
Network.dat	Stoichiometric array for the transcription and translation reactions
SolveBalances.jl	Solves the material balance equations using ODE solvers from the ODE package
Utility.jl	Encodes utility functions required for sensitivity analysis (e.g., computation of the Jacobian)