Chemical Relations

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.

License

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

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.
export/: Final results exported by combining the ChEBI OBO information with the manually curated resources in resources/
- export/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

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

Run either python curate_chebi_relations.py or tox -e mesh to get a list of possible curatable rows. For example:

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      ?       ?       ?       ?       ?

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
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.
Run tox -e lint to make sure you didn't make a mess
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

Summary

There are 829 curated roles as of export on Sun Jun 7 13:37:55 2020

Modulation	Count
activator	15
agonist	87
antagonist	94
inhibitor	625
inverse agonist	2
modulator	6

Target Entity Type	Count
biological process	42
chemical	14
molecular function	39
organism	9
phenotype	15
protein	124
protein complex	14
protein family	572

Target Database	Count
chebi	13
ec-code	499
efo	11
fplx	39
go	88
hgnc	109
hgnc.genefamily	9
hp	6
interpro	1
mesh	27
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

ddomingof/chemical-roles