Friday, May 10, 2013

Linking WikiPathways to binding affinity data

WikiPathways is a long established project (doi:10.1371/journal.pbio.0060184), and while in beta provides a rich resource on various biological processes, in various species. Open PHACTS (Andra particularly) is working on integrating this data. Obvious links include the proteins listed in pathways, which are targeted by compounds in, for example, ChEMBL, one of the resources in the Open PHACTS cache.

However, drugs and drug-like molecules are not abundant in WikiPathways. Some are, like morphine in this metabolism pathway:

However, it seem more common that drug-like compounds are indirectly found pathways. For example, angiotensin-converting enzyme inhibitors (ACE inhibitor, in red below) are mentioned in pathways:

An example ACE inhibitor is captopril. The current BridgeDB-based identifier mapping (doi:10.1186/1471-2105-11-5) will not link the ChEBI identifier for ACE inhibitors (ChEBI:3380) to the matching ChEMBL entry (CHEMBL1560). Thus, we cannot make this link directly.

However, we're in a semantic world, and ontologies come to the rescue, in particular, the ChEBI ontology (doi:10.1093/nar/gkm791). The following screenshot shows how ChEBI says captopril is an ACE inhibitor:

So, if we can only make a claim that any of those listed specific drugs is a ACE inhibitor, then we can use that information to link captopril to the WP557 pathway.

Christian Brenninkmeijer and Alasdair Grey have introduce the concept of lenses in Open PHACTS (see paper below) that define when two things are considered the same. For example, under certain conditions protonation states are the same, while on others not. By turning on and off lenses, you can define what is the same. Lenses can be grouped, and we could have, for example, a "human cell" lens the groups all lenses that details what chemicals are "biologically" identical. For example, because the are readily interconverted under biological (cell) conditions.

So, ChEBI defines a (one-directional) lens that defines captopril is the same as "ACE inhibitor".

Pico, A. R. et al. WikiPathways: Pathway editing for the people. PLoS Biol 6, e184+ (2008). URL
van Iersel, M. et al. The BridgeDb framework: standardized access to gene, protein and metabolite identifier mapping services. BMC Bioinformatics 11, 5+ (2010). URL
Degtyarenko, K. et al. ChEBI: a database and ontology for chemical entities of biological interest. Nucleic acids research 36, D344-D350 (2008). URL
Brenninkmeijer, C. et al. Scientific lenses over linked data: An approach to support task specific views of the data. a vision. In Linked Science 2012 - Tackling Big Data (2012). URL