chemical-roles / chemical-roles

Curation of mechanistic relations from roles in ChEBI and MeSH

Chemical Roles Graph (CRoG)

This repository is meant to house links between ChEBI terms describing various types of inhibitors and their targets in other vocabularies. For example, there are several enzyme inhibitors that refer to ExPASy enzyme class codes, but there are no explicit links in ChEBI to support this.

See also: ebi-chebi/ChEBI#3429

License

• Code in this repository is under the MIT License.
• Data in this repository is under CC0.

Citation

Extension of Roles in the ChEBI Ontology. Hoyt, C. T., Mungall, C., Vasilevsky, N., Domingo-Fernández, D., Healy, M., and Colluru, V. (2020). chemRxiv, 12591221.

Repository Structure

• resources/: Manually curated resources
  • resources/xrefs.tsv: Structured annotations of ChEBI entries describing the relationship to an external vocabulary. For example, the term CETP inhibitor (CHEBI:49205) describes the inhibition relationship to CETP (hgnc:1869).
  • resources/reclassification.tsv: Suggestions on which entities inherit from the wrong type of ChEBI inhibitor role.
• docs/_data: Final results exported by combining the ChEBI OBO information with the manually curated resources in resources/
  • relations.tsv: A combination of the manually curated resources and reasoning (TODO) over FamPlex, InterPro, GO, HGNC Gene Familes, and ExPASy to generate new relationships between instances of the roles curated here.
• curate_chebi_relations.py: The python script that suggests new curation using Gilda and generates the derived resources in export/

Contributing

1. Fork the repository and clone it with:

git clone https://github.com/<your github username>/chemical-relations.git
cd chemical-relations
pip install -r requirements.txt

2. Run either tox -e chebi to curate ChEBI terms that Gilda was able to look up, tox -e chebi-ungrounded to curate all ChEBI terms, or tox -e mesh to curate MeSH. For example, the output tox -e mesh will include something like:

mesh D064449 Sequestering Agents agent   ?   ?   ?   ?   ?
mesh D015842 Serine Proteinase Inhibitors    inhibitor   ?   ?   ?   ?   ?
mesh D058825 Serotonin 5-HT1 Receptor Agonists   agonist ?   ?   ?   ?   ?
mesh D058829 Serotonin 5-HT1 Receptor Antagonists    antagonist  ?   ?   ?   ?   ?

3. Copy/paste the rows you want to curate into the end of resources/xrefs.tsv. Fill out the last 5 columns, which are:
   1. modulation (the relationship)
   2. type (the type of the target)
   3. target_db
   4. target_id
   5. target_name
4. If you find rows that should be blacklisted in MeSH, add them to the blacklist in curate_mesh_relations.py. If You find irrelevant rows while curating ChEBI, add them to resoures/irrelevant_roles.tsv. This will be reorganized to be more consistent for MeSH soon.
5. Run tox -e lint to make sure you didn't make a mess
6. Make a PR back to https://github.com/chemical-roles/chemical-roles.git

Data Sources

Automatically Retrieved Data Sources

• ChEBI (https://www.ebi.ac.uk/chebi)
• HUGO Gene Nomenclature Committee at the European Bioinformatics Institute. See https://www.genenames.org/ for more information
• UniProt (https://www.uniprot.org)
• FamPlex (https://github.com/sorgerlab/famplex)
• ExPASy (https://www.expasy.org/)

Manually Referenced Data Sources

• Gene Ontology (http://geneontology.org)
• EFO (https://www.ebi.ac.uk/efo)
• NCIT (https://ncit.nci.nih.gov)

Summary

There are 836 curated roles as of export on Mon Feb 22 19:33:50 2021

Modulation	Count
Activator	15
Agonist	87
Antagonist	94
Inhibitor	629
Inverse Agonist	2
Modulator	9

Target Entity Type	Count
Biological Process	42
Chemical	14
Molecular Function	39
Organism	9
Phenotype	15
Protein	126
Protein Complex	15
Protein Family	576

Target Database	Count
chebi	13
eccode	499
efo	11
fplx	43
go	88
hgnc	110
hgnc.genefamily	9
hp	6
interpro	1
mesh	29
ncbitaxon	9
ncit	1
pr	15
uniprot	2

Axioms

One of the main goals of this repository is to provide a framework for reasoning over roles (or families) in ChEBI that don't have enough metadata.

Chemical-Physical Entity and Chemical-Process

This repo annotates relationships between chemical role X and protein Z such that:

• X isA chebi:agonist
• Y hasRole X
• Y agonistOf Z

It can also be reasoned over the hierarchy of children of chemical Y such that:

• X isA chebi:agonist
• Y hasRole X
• Y agonistOf Z
• y isA* Y
• y agonistOf Z

This repo annotates relationships between chemical role X and protein family Z such that:

• X isA chebi:agonist
• Y hasRole X
• Y agonistOf Z
• z isA* Z
• Y agonistOf z

And a combination of both the hierarchy of children of chemical Y and the children of protein family Z such that:

• X isA chebi:agonist
• Y hasRole X
• Y agonistOf Z
• y isA* Y
• z isA* Z
• y agonistOf z

In general, this repository maps many ChEBI roles R to relationships r such that:

• X isA R
• Y hasRole X
• R roleHasRelation r
• Y r Z
• y isA* Y
• z isA* Z
• y r z

Chemical and Activity

This repo annotates relationships between chemical role X and activity A such

• X hasRole R
• R roleHasActivityRelation ar
• X ar A

When this is true, we can further infer the action of chemical role X on protein P that has activity A:

• R roleHasEntityRelation er
• P isA protein
• P hasActivity A
• X er P