DOME, developed by Dutt lab, ACTREC-TMC
GUI code is contributed by Rohit Mishra.
An algorithm to prioritize low-frequency somatic mutations integrating somatic mutation propensity, mutation distribution across domain and functional and biochemical residue context within protein structures.
DOME is developed using python3 and R shiny package. The database is provided as a Tabix indexed (.tbi) TSV file along with the toolkit package for download.
Users are required to download DOME package from the webpage. Approximately 2 GB of system space is required to store the package. The downloaded package needs to be extracted using "unzip" or "winrar" extractor, depending on the operating system used. The package contains the following contents:
DOME-main (root folder)
├── Manual (User Manual)
├── app.R (Rshiny App)
├── input_dome.txt (example: input file)
├── output (test output)
├── domeenv.yml (conda environment)
└── scripts (DOME algorithm and accesory scripts)
DOME requires reference databases, which need to be downloaded clicking the following link: DOME reference databases. Click on "Download" (select standard download), the file is 1.44 Gb in size. Place the downloaded "data.zip" in the root folder (dome) and unzip using 'unzip' command or any zip file extractor. DOME is now ready for installation.
System Prerequisites:
The installation of the required packages is performed through Anaconda/Miniconda, which needs to be installed. With Conda installed, users can use the following commands in the Linux / Unix environment to install the required python packages.
DOME can be downloaded from this webpage. Untar the downloaded .zip file using the following command:
unzip dome_v02.zip
cd DOME-mainMake sure that the complete 'unzipped' data directory is present in the dome home directory before proceeding with the further installation and running dome. In the home directory of DOME (DOME-main), run the following command:
conda env create -f domeenv.ymlThis installs all the dependencies and tools required to run DOME.
For running any script pertaining to DOME, make sure that the domeenv Conda environment is activated. More information about Conda environments can be found here
The required scripts to run DOME are placed in the “script” directory.
To run DOME as a command line program, use the following commane: In Linux terminal:
$ conda activate dome
$ cd DOME-main/scripts
$ python3 metaaccesor.py <input_csv>Format of the above mentioned "input_csv" should be as shown below. The CSV format file should contain 3 columns (column 1 - uniprot entry name of the protein; column 2 - amino acid position; column 3 - ALTERED amino acid) and may contain multiple rows (user defined). An example of the file contents is shown below :
EGFR_HUMAN,858,R
ERBB4_HUMAN,931,Y
EGFR_HUMAN,829
TF7L2_HUMAN,365
EGFR_HUMAN,790,M
**To load the R Shiny based GUI or via web-browser use the following command: **
In Linux terminal:
$ conda activate domeenv
$ R -e "shiny::runApp('app.R', launch.browser = TRUE)"
In Windows CMD:
> "Path/to/R.exe" -e "shiny::runApp("app.R", launch.browser = TRUE)"Once users executes the above commands DOME toolkit GUI appears.
Following are the detailed description for each of the tabs-
-
File Upload
Gene based or mutation (position) based search returns a table containing the following columns:
| Column names | Description |
|---|---|
| DOME Pred | Prediction based on the DOME Score. The mutations reported as either hotspot or resistant mutations in the DOME database are flagged as "Hotspot" or "Resistant". The mutations scoring greater than 0.7 DOME Score are termed as "High confidence" and ones scored below 0.7 are flagged "Moderately scored". |
| Entry name | Entry name of protein as per Uniprot database |
| Position | Amino acid position in the protein |
| Reference | Reference amino acid in the protein |
| Altered | Altered amino acid in the protein |
| Domain | Domain name |
| Mutation type | H - hotspot, R - resistant, '-' - not present in significant mutation database |
| Analogous to | Query protein position is analogous to this known significant mutation |
| CADD | CADD score (converted functional score, as described in manuscript) |
| COSMIC count | Mutation count in the COSMIC database |
| ClinVar | Mutation reported in ClinVar |
| Site | A functional site as described in Uniprot database |
| Phosphosite | A site defined in PhosphoSite database |
| Proximity to significant | Geometrical (3D) proximity to a significant mutation (hotspot/resistant) |
| Proximity to functional site | Geometrical (3D) proximity to a functional site described in Uniprot |
| Proximity to PSP site | Geometrical (3D) proximity to a site defined in PhosphoSite database |
| Proximity to 3D hotspot | Geometrical (3D) proximity to a defined 3D hotspot (hotspotdb) |
| Is interface | Residue is a part of a defined protein interface (3D PIP database) |
| Entropy | Entropy score (refer methodology) of the residue within domain |
| DOME Score | Score computed using the DOME algorithm scoring metric (scaled 0-1) |