Drug to Target/Gene/Protein Interaction Databases

Question

[Wayne]

Hello all. I have a list of genes identified in a HiSeq sequencing run that are related to cancer. I would like to intersect this list with a database of known drug-drug target interactions so that if a drug is known (but not necessarily approved) to target a particular gene (protein) I can identify it. Does anyone know the best way to go about doing this.

i.e... what is the best database or resource for this?

Any help would be greatly appreciated!

[Malachi Griffith]

@Wayne. Please let us know if you have any enlightening experiences with one or more of the resources listed below...

Answer 1

[Malachi Griffith]

There are many, many options. You can break the various resources into several categories depending on the type of drug-gene interaction you are interested in and the type of evidence used to characterize the interaction. I have listed these categories and some options for each.

UPDATE: DGIdb - A resource for mining the druggable genome

This resource was created by our group specifically to address this question. It was initially published in Nature Methods (2013) an update paper was published in NAR (2016), and another update was published in NAR (2017).

DGIdb offers a meta-database to pull many of the concepts describe above together. It provides an intuitive web interface for biologists/clinicians and an API for bioinformaticians wishing to automate this kind of analysis. A press release with a lay description of its goals can be found here.

'Known' drug-gene interactions (often based at least partially on mining published literature):

• CIViC (clinical interpretation of variants in cancer)
• Drug Target Commons
• DrugCentral
• Pharos
• DrugBank (provides a complete dump of their database in XML format)
• Therapeutic Target Database, TTD. (provides a complete dump of their database as flat files)
• The NCI Cancer Gene Index (XML documentation here])
• ClinicalTrials.gov (Can be queried via XML)
• Kegg Drug
• PharmGKB
• STITCH2
• SuperTarget
• MetaDrug
• Cancer Resource
• Comparative Toxicogenomic Database (CTD)
• My Cancer Genome
• CancerCommons
• IUPHAR/BPS Guide to Pharmacology
• Rask-Andersen et al., 2014

Potentially druggable genes (genes that have characteristics that make them good drug targets but do not necessarily have a drug yet):

• Hopkins and Groom, 2002
• Russ and Lampel, 2005
• Sophic
• Kinase.com
• Kinopedia
• Southan et al., 2011
• Munos, 2013

Drug response interactions (genes that influence response but are not necessarily the direct target of the drug - includes side effects, sensitivity, and resistance information)

• T3DB
• Genomics of Drug Sensitivity in Cancer
• SuperCYP
• SIDER

Empirical drug gene interaction data (databases containing results of high throughput compound library screening assays)

• PubChem
• The Binding Database

[ben.mcgee.good]

Are there any public meta-databases that pull all of this together ?

[Malachi Griffith]

Welcome to Biostars Ben. ;). We have been working on exactly such a public meta-database and web service. Still in Beta but you can find it here: dgidb.org

[Malachi Griffith]

This came out to a long list. Just to be clear for @Wayne's specific question, if you are in a hurry and want to get going quickly I would recommend DrugBank as a starting point.

[Malachi Griffith]

Update. Now I would recommend DGIdb as a starting point.

[Ron]

hello @Malachi Does this database (http://dgidb.org/downloads ) includes information from the resources listed above? or could you provide info on how it was created ? I read this page and http://dgidb.org/getting_started "drug-gene interactions have been mined from DrugBank, therapeutic target database (TTD), PharmGKB", however the downloads page provides data from drugbank separately.

[Mo Sander]

Another resource that provides detailed information about measured small molecule - protein interactions is the ChEMBL database, see https://www.ebi.ac.uk/chembldb/ .

[Chirag Nepal]

Thanks for the info and nice tool DGIdb. However, if i have a set of genes (groupA, groupB and so on) as input and want to see enrichment (or p-value) of certain kinds of drugs in these groups. I tried DGIdb, it provides information at the gene level. Any suggestions. Thank you !

Answer 2

[Larry_Parnell]

And after searching the various databases, you should run against SIDER. SIDER contains information on marketed medicines and their recorded adverse drug reactions. The information is extracted from public documents and package inserts. The available information include side effect frequency, drug and side effect classifications as well as links to further information, for example drug–target relations.

Added in edit on 15 Mar 2012: I would add the work of Altman et al to this. They have just published a paper on the effects and interactions of various commonly taken drugs by mining hundreds of thousands of adverse events reported to the US Food and Drug Administration (FDA) each year. You'll be most interested in their comprehensive database of drug effects (Offsides) and a database of drug-drug interaction side effects (Twosides).

[Obi Griffith]

This is great information and something we would like to incorporate into future versions of dgidb.org.

Answer 3

[Rashedul Islam]

A good review published earlier 2018 on this topic summarized the updates of databases and methods.

Yongjun Zhu et. al; Drug knowledge bases and their applications in biomedical informatics research. Brief Bioinform. 2018 Jan 3.