DART is a user-friendly, open source software tool to provide practitioners with all relevant information to support confident genetic discovery in compliance with emerging community standards.

Architecture

DART is composed by different systems:

• Back End:
  • Variant data is stored in a mongoDB instance to allow a flexible data format together with BED files (panels) data and Coverage data
  • The list of loaded files together with users, permissions and reports are stored in a MySQL server
• Core:
  • The backend is accessed through the service layer which communicates with mongoDB using the Mongo Java driver and with MySQL using Hibernate
  • The core of the DART web app is the controller layer which manages the communication between the consumer and the service layer
• API:
  • The data is accessed via a REST API which communicates to the Back-End via the controller
• Core+API are packaged together into a single EAR file
• Web application:
  • The application exposed to the user is written in JavaScript using the Angular framework. The app is packaged in a WAR file
• Cache:
  • The caching of the queries and query results is performed via Infinispan and cache data is persisted on the MySQL database
• Web server:
  • The application (EAR + WAR) is deployed on a JBOSS wildfly application server. Static content is served by the undertow subsystem and security is managed by the elytron component.
  • All the configuration is deployed in the standalone.xml file
• Loader:
  • The loader is a java executable which reads and parses the VCF files and inserts the variants into the Back-End through Java Remote Procedure Calls

Quick installation

PRE-REQUISITES

• You must have DOCKER installed and running on your machine: for LINUX please be sure that both the docker and docker-compose packages are installed

INSTALLATION

Download the lastet release binary DART-server-1.0.0-install.tar.gz and extract it:

tar -xzvf DART-server-1.0.0-install.tar.gz 

DO NOT remove the installation folder DART-server-1.0.0 since all the data resides here!

In the DATA folder of the installation folder you will find:

• A log folder where the application server logs are written
• A mongo folder where the mongodb files are written
• A mysql folder where the mysql files are written
• A projects folder where your project data reside

USAGE

START the application server

To start the application server you can use the start script:

bash DART-server-1.0.0/start.sh

Please note that the server log is under DATA/log/server.log. The server can take some time before being up and running.

Install demo data

To load data on your local installation of DART you should create a project in your installation folder under DATA/projects and then run the loader (the application server must be running - see usage instructions below)

1. To download and set our demo trio project (https://doi.org/10.5281/zenodo.4314874), you can use the following:

cd DART-server-1.0.0
wget --no-http-keep-alive https://zenodo.org/record/4320863/files/DART_Demo_Trio.tar.gz
tar -xzf DART_Demo_Trio.tar.gz

2. Once the project is set in the DATA/projects folder you can load it in DART using the command

docker exec -it dart-server './bin/dart_loader/loader.sh' 'DART_Demo_Trio'

USE the tool

Open your browser (tested on Google Chrome on MacOS) on localhost:8080 and login using the credentials:

• User: DART_user
• Password: changeme

You can refer to the online documentation for usage details.

STOP the application server

To stop the application server you can use the stop script:

bash DART-server-1.0.0/stop.sh

UN-INSTALLATION

1. Remove all the docker images (container are removed by the stop script)

docker image rm org.open.medgen/dart-server:1.0.0_local

2. Remove all the data stored locally

rm -r DART-server-1.0.0

Build from repository

Prerequisites

• npm
• nodejs
• mvn (min. 3.3.9)
• openJDK 8
• git
• Docker and Docker compose

Build profiles

To allow for a flexible development different maven build profiles are available:

• server: packages the wildfly application server and deploys the standalone.xml configuration for DART (compile phase)
• front-end: packages and deploys the front-end WAR (angular app) (package phase)
• back-end: packages and deploys the back-end EAR (JAVA REST API + Core) (package phase)
• loader: packages and deploys the loader application and script (deployed in the bin/dart_loader folder of the application server) (package phase)
• package-docker: creates a docker image for the server and the installation binary

The wildfly web server is built and configured in DART-server/target/DART_install.

Configuration details

The pom.xml file of the DART project contains default values for all username / passwords. Most values can be overwritten using the specified environment variables further described below. Properties without an environment variable can not be changed after compilation (running mvn install ...).

pom property name	environment variable	Description
dart.application.user	DART_LOADER_USER	Dart login user name
dart.application.user.group	DART_LOADER_GROUP	Dart user group
dart.application.user.first_name	-	Dart user first name
dart.application.user.last_name	-	Dart user last name
dart.application.user.email	-	Dart user email
dart.application.user.password	DART_LOADER_PASSWORD	Dart user password
dart.wildfly.admin.user	DART_WILDFLY_ADMIN_USER	Wildfly admin user
dart.wildfly.admin.password	DART_WILDFLY_ADMIN_PWD	Wildfly admin password
dart.mongo.server	DART_MONGO_SERVER	MongoDB DART server URI
dart.mongo.admin.db	DART_MONGO_ADMIN_DB	MongoDB admin db
dart.mongo.admin.user	DART_MONGO_ADMIN_USER	MongoDB admin user
dart.mongo.admin.password	DART_MONGO_ADMIN_PWD	MongoDB admin password
dart.mongo.db	DART_MONGO_DB	MongoDB DART database name
dart.mongo.user	DART_MONGO_USER	MongoDB DART user
dart.mongo.password	DART_MONGO_PWD	MongoDB DART user password
dart.mongo.query_limit	DART_MONGO_QUERY_LIMIT	MongoDB query result limit
dart.sql.server	DART_SQL_SERVER	MySQL server URI
dart.sql.params	DART_SQL_PARAMS	MySQL connection parameters
dart.sql.db	DART_SQL_DB	MySQL database name
dart.sql.admin.user	DART_SQL_ADMIN_USER	MySQL admin user
dart.sql.admin.password	DART_SQL_ADMIN_PWD	MySQL admin pwd
dart.sql.user	DART_SQL_USER	MySQL DART user
dart.sql.password	DART_SQL_PWD	MySQL DART password
dart.web.server.production	-	DART running in production (true/false)
dart.web.server.base.url	-	DART base URL e.g. localhost:8080
dart.web.server.protocol	-	DART server protocol e.g. http
dart.web.server.api.url	-	DART web url api ${dart.web.server.protocol}://${dart.web.server.base.url}/DART-API/
dart.web.server.static.url	-	DART static web content url e.g. ${dart.web.server.protocol}://${dart.web.server.base.url}/static/
dart.web.server.url	-	DART final web API URL e.g. http://localhost:8080/DART-API/
dart.web.base.href	-	DART path in URL e.g. / or /my/personal/research/dart/

Build instructions

Download this repository git clone https://github.com/DanieleBarreca/BSF_DART.git

1. Build DART

• Go to the source code root: cd BSF_DART
• Decide on the URL, where DART will be accessible from (dev profile points to localhost:8080/)
• Prepare and package all resources in different modes

1.1. Build DART with default values

• Use default values using mvn clean install -P server,front-end,back-end,loader,package-docker

1.2. Build DART with custom values

• Customize your final server URLs by providing properties:

mvn clean install -P server,front-end,back-end,loader,package-docker \
 -Ddart.web.server.production=true \
 -Ddart.web.server.url=http://my-dart.int.cemm.at:8080/DART-API/ \
 -Ddart.web.base.href=/

2. Run DART

You can run DART from the DART-server/target/DART_install via Docker using the start.sh and stop.sh scripts (see USAGE section).

Alternatively, you can start mongodb and mysql using the DART-server/target/DART_docker/docker-compose-Dev.yml docker compose file and run the server manually from the DART-server/target/DART_docker/wildfly_custom_17 folder. In this case it is important to make sure that both the DART_MONGO_SERVER and DART_SQL_SERVER variables in the DART_server/target/DART_install/default.env file point to localhost.

1. Set the environment

cd DART_server/target/DART_docker

docker-compose -f docker-compose-Dev.yml up -d

set -a
source ../DART_install/default.env
set +a

2. Manually run the server:

## add admin user + start server
bash dart-entry-point.sh

In this case the loader is located in the DART-server/target/DART_docker/wildfly_custom_17/bin/dart_loader folder and projects are served from the DART-server/target/DART_docker/wildfly_custom_17/static-content folder

Resources used in this work

The Loader uses resources from the following resources to annotate somatic variants:

• CIViC Griffith, M., Spies, N., Krysiak, K. et al. CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer. Nat. Genet 49, 170-174 (2017)
• Cancer Hotspots Chang, M., Asthana, S., Gao, S. et al. Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity. Nat Biotechnol 34, 155–163 (2016)
• 3D Hotspots Gao J, Chang MT, Johnsen HC, Gao SP, Sylvester BE, Sumer SO, Zhang H, Solit DB, Taylor BS, Schultz N, Sander C. 3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets. Genome Med. 2017 Jan 23;9(1):4

The Orphanet Rare Disease Ontology (ORDO) is loaded in the MySQL DB as reference ontology for disease annotation.

Libraries and 3rd party software

All the libraries used in the build are and their licenses are listed in the license folder.