Boolean networks allow us to give a mechanistic explanation to how cell types emerge from regulatory networks. However, inferring the regulatory network and its functions is complex problem, as the available information is often incomplete. rGriffin
uses available biological information (regulatory interactions, cell types, mutants) codified as a set of restrictions and returns the Boolean Networks that satisfy that restrictions. This Boolean networks can then be used to study the biological system.
The rGriffin
package is an R connector to Griffin
(Gene Regulatory Interaction Formulator For Inquiring Networks), a java library for inference and analysis of Boolean Network models. Griffin
takes as inputs biologically meaningful constraints and turns them into a symbolic representation. Using a SAT engine, Griffin
explores the Boolean Network search space, finding all satisfying assignments that are compatible with the specified constraints. TherGriffin
package includes a number of functions to interact with the BoolNet package.
We recommend using the rGriffin docker.
Install docker in your system
Run the following command from the terminal, change mypassword for a password you select, and the path (/home/user/tmp/) to an existing path in you local file system, you can also change /home/rstudio/tmp to a different location but keep the base path /home/rstudio/
docker run --rm -e PASSWORD=mypassword -p 8787:8787 -v /home/user/tmp/:/home/rstudio/tmp stanmoon/rgriffin
The container will be removed when it exits, but this can be changed by removing de --rm option. See more options in the docker documentation.
rGriffin depends on R, Java, rJava, and BoolNet.
Install R (>=3.1) and java. We recommend Oracle JDK 8.
Install rJava and devtools using the R console. While rJava should be authomatically instaled with rGriffin, the installation of rJava is succeptible to mistakes, so it is best to install it first.
> install.packages("rJava")
> install.packages("devtools")
> devtools::install_github("mar-esther23/rgriffin")
To see more details about the installation in specific operative systems see the issues
Let us suppose a cell, we know that this cell has three proteins called a, b and c. We know that a activates b and that b and c inhibit each other. We also suspect that b and c may have positive self-regulatory loops. We can add this interactions to the table as “OPU” (optional, positive, unambiguous). This dataframe is the topology of the network.
Source | Target | Interaction ---|---|--- a | b | + b | c | - c | b | - b | b | OPU c | c | OPU
Suppose we also have some information of what cell types have been observed. For example, there is a cell type that expresses b, but not a or c and an other cell type that expresses c, but not a or b. There might exist a third cell type that has not been fully characterized where we know that the cell expresses no a or c but we have NO information on b. This dataframe is the attractors of the network.
a | b | c ---|---|--- 0 | 1 | 0 0 | 0 | 1 0 | * | 0
We can then use this information to create a query. rGriffin
can include other types of information like transition between cell type, cycles, transitions between cell types or mutant cell types.
library("rGriffin")
genes = c('a','b','c')
inter = data.frame(source=c('a','b','c','b','c'),
target=c('b','c','b','b','c'),
type=c('+','-','-','OPU','OPU'),
stringsAsFactors = F )
q = createGqueryGraph(inter, genes)
attr = data.frame(a=c(0,'*',0),
b=c(0,1,0),
c=c(0,0,1),
stringsAsFactors = F )
q = addGquerySteadyStates(q, attr)
Then we can use Griffin
to find the networks that behave according with our biological information.
nets = runGquery(q)
nets
"targets,factors\na,false\nb,((((((!a&b)&!c)|((!a&b)&c))|((a&!b)&!c))|((a&b)&!c))|((a&b)&c))\nc,(!b&c)\n",
"targets,factors\na,false\nb,((((((!a&b)&!c)|((a&!b)&!c))|((a&!b)&c))|((a&b)&!c))|((a&b)&c))\nc,(!b&c)\n",
"targets,factors\na,false\nb,(((((!a&b)&!c)|((a&!b)&!c))|((a&b)&!c))|((a&b)&c))\nc,(!b&c)\n",
"targets,factors\na,false\nb,((((!a&b)&!c)|((a&!b)&!c))|((a&b)&!c))\nc,(!b&c)\n",
"targets,factors\na,false\nb,((((!a&b)&!c)|((a&b)&!c))|((a&b)&c))\nc,(!b&c)\n"
There are multiple options to integrate BoolNet
and rGriffin
. The function getNetTopology()
can obtain the topology with interaction signs of a BoolNet network. The function attractorToDataframe()
can be used to export a BoolNet attractor as a dataframe that rGriffin
can use. The function runGquery()
includes the option return=’BoolNet’
, that return the inferred networks as BoolNet
networks.
The development of Griffin
began in 2013 as a PAPIIT (Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica) project to solve the inference of Boolean Network models for the Arabidopsis thaliana root stem cell niche. It continued in 2015 with support of Conacyt grant 221341.
In January, 2017 we organized a course in C3-UNAM to teach biologist how to use Griffin
. We received two main comments: the input format was too complicated and it was uncomfortable to use the output with other packages. After some consideration we decided to create an R
wrapper that could export and import BoolNet
networks. We selected BoolNet
as it has an good documentation and the package BoolFilter
had been designed to work with it.
The development of rGriffin
began during the EOBM 2017 in CUIB. For the following year we continued developing rGriffin
as our schedules allowed. There were multiple challenges during the development: defining user-friendly inputs, using Rjava
, and structuring the package. In August 2018, we attended the TIB2018-BCDW where we received valuable guidance from Martin Morgan and Benilton S Carvalho. It was during this workshop that the first version of rGriffin
was finished.
We created a docker to simplify the installation and solved some minor errors during 2021.
We hope to continue developing Griffin
and rGriffin
. If you have ideas, suggestions or bugs, please contact us at Github.
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