Pharmacoracle

Contents

Pharmacoracle - a REST API

The Pharmacoracle contains data from OWL ontologies that are based on CPIC recommendations provided by the PharmGKB API, and which have been further curated to satisfy the needs of the Department of Pharmacology at Oslo University Hospital.

The Pharmacoracle was implemented as an attempt to understand the field of pharmacogenomics, based on data from PharmGKB, and solving the same problem as PharmGKB's PharmCAT software PharmCAT software, but in the context of the technology and clinical recommendations of our clinic.

Pharmacoracle version 1

The first version of the Pharmacoracle is based on the OWLAPI Queries to Pharmacoracle have to be written in the Manchester syntax in the same way as for the DL Query Tab of Stanford's desktop Protégé. The choice of technology was inspired by the Ontology-Based, Mobile-Optimized System for Pharmacogenomic Decision Support at the Point-of-Care of the UPGx project. The ontology of Mathias Samwald is at the core of this system. They use the TrOWL reasoner instead of the HermIT reasoner that is at the core of Pharmacoracle.

The Pharmacoracle infrastructure is written in Python, and the OWLAPI is invoked from Python via Pexpect. For curation, a link between OWL classes and Python is provided by Jean Baptiste Lamy's Owlready2, which we use to translate PharmGKB's JSON-LD to OWL.

The Pharmacoracle is used in our PGx analysis script Pharmacolyzer, but can also be used directly.

Hints on how to use Pharmacoracle (version 1)

In order to write queries to an OWL ontology we need to know the names of the OWL elements, notably OWL Properties (e.g. has_haplotype) and and OWL Classes (e.g. TPMTstar3A).

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In addition we need to know the Manchester expressions of cardinality that are used to connect OWL Properties and OWL Classes, in particular:

Cardinality word	Cardinality	Explanation
some		Connects a property to at least one class, e.g. has_haplotype some TPMTstar3A
exactly	number	Connects a property to an exact number of classes, e.g. has_haplotype exactly 1 TPMTstar3A
min	number	Connects a property to a minimum number of classes, e.g. has_haplotype min 1 TPMTstar3A

For each query we add a code word to indicate the relationship between our query and the desired answer (cf. the DL Query tab in the desktop version of Stanford's Protégé), as explained in this table:

Code word	Relationship
SubClasses	Get elements that contain the query (but not equivalent to the query)
DirectSubClasses	Get only the SubClasses that are closest to the query
EquivalentClasses	Get only elements equivalent to the query
SuperClasses	Get elements that contain parts of the query (but not the entire query and not equivalent)
DirectSuperClasses	Get only the SuperClasses that are closest to the query

In order to query the Pharmacoracle automatically, we have made a Python script Pharmacolyzer that returns dosing recommendation based on a pharmacotyped patient VCF.

Examples of use

Find the PGx alleles that contain the variant snpC>T at chr6:18139228

curl https://www.pgx.no/api/pharmacoracle -d "query=SubClasses:snpCtoT_at some chr6_18139228"

Find the PGx allele that is identical to the variants snpC>T at chr6:18139228 and snpT>C at chr6:18130918

curl https://www.pgx.no/api/pharmacoracle -d "query=EquivalentClasses:(snpCtoT_at some chr6_18139228) and (snpTtoC_at some chr6_18130918)"

Find the PGx alleles that contain either snpC>T at chr6:18139228 or snpT>C at chr6:18130918

curl https://www.pgx.no/api/pharmacoracle -d "query=DirectSuperClasses:(snpCtoT_at some chr6_18139228) and (snpTtoC_at some chr6_18130918)"

Find the Azathioprine TPMT functional status of the TPMT*3B allele:

curl https://www.pgx.no/api/pharmacoracle -d "drugs=azathioprine&query=SuperClasses:has_haplotype some TPMTstar3B"

Find the Azathioprine dosing recommendations for a patient with two Azathioprine TPMT No Function alleles:

curl https://www.pgx.no/api/pharmacoracle -d "drugs=azathioprine&query=EquivalentClasses:has_phenotype some (has_function exactly 2 AzathioprineTPMT_NoFunction)"