Predicting the impact of mutations on kinase-substrate phosphorylation in R

Installation

To install MIMP, first make sure your R version is at least R 3.0. You can check by typing the following into your R console:

R.Version()$major

Next, install and load devtools package:

install.packages("devtools")
library("devtools")

Then download and install the rmimp package from github (this may take a few minutes, please be patient):

install_github("kvnkuang/rmimp")

Load the rmimp package into R, and you're ready to go!

library("rmimp")

Running MIMP on sample data:

To start using MIMP, try loading paths to the sample data, which come with the package:

# Get the path to example mutation data 
mut.file = system.file("extdata", "sample_muts.tab", package = "rmimp")

# Get the path to example FASTA sequence file 
seq.file = system.file("extdata", "sample_seqs.fa", package = "rmimp")

# Get the path to example FASTA sequence file 
psite.file = system.file("extdata", "sample_phosphosites.tab", package = "rmimp")

The mutation file contains the following lines:

TP53 R282W
TP53 R248P
TP53 W146S
CTNNB1 S33C
CTNNB1 S37F

The phophosite file contains the following lines:

TP53	284
TP53	215
CTNNB1	33

To start the analysis, simply run the mimp function on these files:

# Run rewiring analysis
results = mimp(mut.file, seq.file, psite.file, display.results=TRUE)

The output is stored in the results variable and should show up in your browser. To suppress browser display, set display.results=FALSE

If you'd like to redisplay the results in your browser at a later time, run the following:

results2html(results)

Running MIMP without phosphosite data:

If you don't pass phosphosite data to the function call, MIMP will use positions of all S, T and Y residues in your FASTA file as potential phosphosites.

# Run rewiring analysis
results2 = mimp(mut.file, seq.file, display.results=TRUE)

Running MIMP without phosphosite or sequence data:

If you pass only a mutation file to the function call, MIMP will use positions of experimentally identified phosphosites from PhosphoSitePlus, and their corresponding sequences. PhosphoSitePlus uses UniProt accessions as identifiers, so for this please make sure the IDs used in your mutation file are uniprot accessions:

Here's an example using a file with five mutations:

P04637 R282W
P04637 R248P
P04637 W146S
P35222 S33C
P35222 S37F

# Get the path to example mutation data 
mut.file.up = system.file("extdata", "sample_muts_uniprot.tab", package = "rmimp")

# run mimp
results3 = mimp(mut.file.up, display.results = TRUE)

Documentation

For a full list of all options, take a look at the documentation by typing the following in your R console:

?mimp

Contact

If you have any feedback, suggestions or questions, please drop me a line at (wagih(at)ebi.ac.uk) or open an issue on github.