This repository is associated with the study disclosed in manuscript:

Zahoranszky-Kohalmi et al., A Workflow of Integrated Resources to Catalyze Network Pharmacology Driven COVID-19 Research.

Preprint https://www.biorxiv.org/content/10.1101/2020.11.04.369041v1. (DOI: 10.1101/2020.11.04.369041)

• A functional instance of the Neo4COVID19 database is accessible here: https://aspire.covid19.ncats.io:7473/browser/

• For detailed information on how to access the database please refer to the instructions posted at https://neo4covid19.ncats.io/ under ACCESS tab.

The workflow was tested successfully on Python version 3.6.9, py2neo version 4, and graph database Neo4j Community Edition version 3.5.6.

1. Install Git Large File Support (Git LFS)

   • Follow instructions to install Git LFS before cloning the Git repository, see: https://git-lfs.github.com/

2. Clone repository

   • Create a working directory "n4ctest" which is in the user's home directory (/home/user/n4ctest in linux, /Users/user/n4ctest on Mac)

   • Change directory to working directory:

     cd ~/n4ctest

   • Clone repo:

     git clone https://github.com/ncats/neo4covid19

   • Change to source code directory:

     cd neo4covid19/code

3. Setting up Conda environment

   • Follow OS specific instructions to install Conda, see: https://docs.conda.io/en/latest/miniconda.html

   • Once Conda is installed, create a clean conda environment (make sure you're in the neo4covid19/code directory of the repository, in this example this location of this directory is ~/n4ctest/neo4covid19/code ):

     if you have a Linux environment, then:

     conda env create -f n4c_env_linux.yml

     if you have a Mac environment, then:

     conda env create -f n4c_env_mac.yml

   • Activate the Conda environment

     conda activate n4c

4. Setting up Neo4j Community Edition database

   • Follow instructions on setting up Neo4j Community Edition for your OS, see: https://neo4j.com/docs/operations-manual/current/installation/
     Make sure you install the Community Edition of Neo4j, and the version you choose to install is 3.5.x. Of note, the workflow was tested on Neo4j Community Edition v3.5.6.
     

   • Example on Ubuntu (see: https://www.digitalocean.com/community/tutorials/how-to-install-and-configure-neo4j-on-ubuntu-20-04)

     sudo apt update
     

     sudo apt install apt-transport-https ca-certificates curl software-properties-common
     

     curl -fsSL https://debian.neo4j.com/neotechnology.gpg.key | sudo apt-key add -
     

     sudo add-apt-repository "deb https://debian.neo4j.com stable 3.5"
     

     sudo apt install neo4j
     

     sudo systemctl enable neo4j.service
     

     sudo systemctl status neo4j.service

   • (Neo4j database web interface will be running on http://localhost:7474/ and Bolt at 127.0.0.1:7687)

   • Update default neo4j password to get the credentials required to build the Neo4COVID19 database with the workflow:

     The default credentials of any Neo4j installation:

     username: neo4j
     password: neo4j

   • To change the default password, either visit http://localhost:7474/ where you will be prompted for changing the password, or connect to command-line client from terminal as described below:

     cypher-shell

     If not prompted for new password, then enter this into client:

     CALL dbms.changePassword('mypassword');

     then enter this:

     :exit

   • Create Neo4j database connection configuration file:

     mkdir -p ~/n4ctest/neo4covid19/cfg

     Assuming that the Neo4j is running locally and that you changed the default password to let's say mypassword, create a db.cfg file in ~/n4ctest/neo4covid19/cfg directory with this content and format (one entry per line):

     localhost
     7687
     neo4j
     mypassword

     If your Neo4j server is not running on localhost then you need to replace localhost with the hostname of the server running the Neo4j database server. The 7687 is the default port for the Neo4j BOLT connection. Replace username and password according to your Neo4j serve configuration.

     Once the db.cfg file is created, you can compile the database. Beware, that the script first deletes ALL existing data from a Neo4j database, so that it can perform a clean build everytime.

     Also, make sure you have the Neo4j database server running and that you have the connection configuration file set up properly. The workflow will wipe the Neo4j database clean. In case you have different data loaded to your Neo4j database (that have different node/relation types), those may not be wiped by the code. In order to assure a clean Neo4COVID19 deployment, you need to make sure that you start from a completely empty database. Please refer to Neo4j documentaion for details (https://neo4j.com/). Once you took care of the database you can proceed with the workflow as shown below.

• Make sure Neo4j server is up and running.

• Make sure that the "n4c" conda environment is active

  conda activate n4c

• Change to source code directory

  cd ~/n4ctest/neo4covid19/code/

Step 1. Data harmonization step

`python harmonize.py`

Please note that the process can take several minutes.

Step 2. Assembling a SmartGraph Network of HATs

If you just want to rebuild the DB skip to Step 3, otherwise continue as follows.

• Go to SmartGraph (https://smartgraph.ncats.io).

• Clear the fields "Start Nodes" and "End Nodes" then click on "clear graph".

• Copy the content of uniprot column in file data/output/sg_proteins_a.tsv. This set of UniProt IDs will be your Start Nodes in SmartGraph (https://smartgraph.ncats.io).

• Copy the content of uniprot column in file data/output/sg_proteins_b.tsv and use them as End Nodes in SmartGraph.

• Set the Max Distance parameter to 3.

• Leave the PPI Confidence Level at its default value, i.e. 0.00.

• Click on "find shortest path".

• Once the network is assmebled in SmartGraph, click on "Download graph", select "Cytoscape JSON", then rename the downloaded file to SG_HATs_dist_3_conf_0.00.json and place the file into data/input/.

• Repeat the SmartGraph analysis by swapping the starting and end nodes to create a "reverse" network.

• Save the results into data/input/ as SG_HATs_reverse_dist_3_conf_0.00.json.

Step 3. Process Data Generated by SmartGraph (in Step 2)

`python process_sg.py`

Step 4. DB Compilation

`python compile.py`

Please note that the process can take several minutes.

Alternatively you can import the precompiled Neo4COVID19 database that is also distributed in this repository (please make sure you have Git LFS support enabled on your system to actually clone the database dump file).

• Importing the Neo4COVID19 Database

1. Stop the Neo4j database.

2. Import the Neo4COVID19 database from the database dump file.

   Example command on a Linux OS:

   neo4j-admin load --from=/home/user/path_to/neo4covid19/data/db/Neo4COVID19_PUB_rolling_neo4j.dump --database=graph.db --force

   Please note that you need to replace the /home/user/path_to/ part of the file path so that it reflects your environment. Also, here we assumed that the name of the Neo4j database is the default graph.db.

   
   If you're using a Mac, replace the */home/user/* of the path by */Users/user/*.

3. Start the Neo4j database.

In case you'd make changes in the Neo4COVID19 database, you can export the Neo4j database into a database dump file as shown below.

• Exporting the Neo4j database

1. Stop the Neo4j database.

2. Dumping the data into a file.

   neo4j-admin dump --database=graph.db --to=/home/user/path_to/neo4covid19/data/db/Neo4COVID19_PUB_rolling_neo4j.dump

   Please note that you need to replace the /home/user/path_to/ part of the file path so that it reflects your environment. Also, here we assumed that the name of the Neo4j database is the default graph.db.

   
   If you're using a Mac, replace the */home/user/* of the path by */Users/user/*.

This repository contains source code, and data and results files which are organized into various subdirectories.

Source code subdirectories:

code/
ci/

Data and results subdirectory:

data/

• Source Code License of neo4covid19 Repository

  The applicable license to source code can be found in the root of the repository under filename: LICENSE.txt . This license is applicable to all files recursively in the Source code subdirectories as defined above. The file NOTES.txt in the root of the repository lists source code modules that were utilized and their respective licenses. These modules have their own licenses which might be different from the Source Code License of this repository, and they need to be respected accordingly.

• Data License of neo4covid19 Repository

  The applicable license to data and results can be found under filename: data/LICENSE.txt . This license is applicable to all files recursively in the Data and results subdirectory as defined above. The file data/NOTES.txt lists input files and resources utilized to compile the Neo4COVID19 and results files that can be considered as derivative work of those resources. These input files and resources have they own licenses which might be different from the Data License of this repository, and they need to be respected accordingly. In the same file we also list which results files can be considered as derivative works, and we also list the the respective ascendent data source(s).

We wish you success in your research to find a cure for COVID-19!

https://stackoverflow.com/questions/56713744/how-to-create-conda-environment-with-specific-python-version https://stackoverflow.com/questions/65254535/xlrd-biffh-xlrderror-excel-xlsx-file-not-supported https://www.digitalocean.com/community/tutorials/how-to-install-and-configure-neo4j-on-ubuntu-20-04 https://debian.neo4j.com/ https://www.markdownguide.org/cheat-sheet/ https://neo4j.com/docs/operations-manual/current/tools/dump-load/ https://stackoverflow.com/questions/41274007/anaconda-export-environment-file https://conda.io/projects/conda/en/latest/user-guide/tasks/manage-environments.html#creating-an-environment-from-an-environment-yml-file https://conda.io/projects/conda/en/latest/user-guide/tasks/manage-environments.html#activating-an-environment