targetDB 1.3.3

Package with an application to generate report on potential drug targets

TargetDB

TargetDB is a tool to quickly query multiple publicly available databases and provide an integrated view of the information available about potential targets. A quick binding pocket search is also performed (using fpocket).

Tutorial: A document containing details on the methods used can be found HERE (pdf)

Installation

Python package installation

Pip installation (Preferred way)

pip install targetDB

Installation will fail due to opentargets dependency - 08/11/2021 (a fix will be needed and/or an opentarget-free version released)

Conda installation

conda create --name targetdb --channel bioconda targetdb
conda activate targetdb
target_DB --help

Python compatibility

python version >= 3.4

Preferred python distribution : Anaconda 3

Database files installation

This package relies on the use of sqlite database to properly function.

Required database

• targetDB

You can download a copy of the database HERE

This database contains all of the human genome genes that have a uniprot ID

System compatibility

• Linux
• Windows
• Mac (not tested)

Usage

targetDB package provides a user interface to use the tool: targetDB

targetDB

When using targetDB for the first time you will be asked to enter information about:

• targetDB sqlite database file
• path to save list output files
• path to save detailed target output files
• email address (used for pubmed searches if none provided no pubmed search will be run)

Those informations will be stored in ~/.targetdb/config.ini

Once created it will automatically start the main user interface (as seen below)

Examples

TargetDB can be used in three modes:

• Single
• List
• Spider plot

Single mode outputs

A series of examples can be downloaded here (Excel file)

• ACHE
• APOE
• BACE1
• Tau
• PSEN1

List mode outputs

In this example we have used a list of 95 targets provided by the AMP-AD consortium (LINK HERE)

You can download two version of the list with different weight used to construct the MPO Score

• AMPAD - Medicinal chemist pioritization
• AMPAD - Structural biologist pioritization

You can also find a list used to prioritize an entire class of proteins (Solute Carrier Protein)

• SLC Prioritization

A definition of all the columns in the output can also be downloaded

• Columns definition

Spider Plots

A spider plot is here used to quickly give an idea of the area in which a target has strength and weaknesses

Here under a guide to help reading these plots:

Instructions to create a targetDB database from scratch

WARNING: This mode is not fully supported and we cannot guarantee it will execute without errors

System compatibility

• Linux

Database creation

target_DB

The list of required databases is :

• ChEMBL v25

ChEMBL sqlite database can be directly downloaded HERE

This mode will generate a targetDB database that can then be used in report mode

Other dependencies for the database creation mode

blast

This mode use blast locally to perform similarity search and sequence alignments

information to download and install blast locally can be found HERE

fpocket

In order to perform binding pocket searches and assess their druggability the program fpocket is used

Vincent Le Guilloux, Peter Schmidtke and Pierre Tuffery, "Fpocket: An open source platform for ligand pocket detection", BMC Bioinformatics, 2009, 10:168

Peter Schmidtke, Xavier Barril "Understanding and Predicting Druggability. A High-Throughput Method for Detection of Drug Binding Sites", J. Med. Chem., 2010, 53 (15), pp 5858–5867

instructions to download and install fpocket can be found HERE

Current version of targetDB works with fpocket3

targetDB will not be able to perform pocket search on windows as fpocket is not available on windows platform