Toxicity Static Demo

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What are the toxicities of metformin and of drugs similar to metformin?

Explanation:In this question we are trying to provide a physician with a comprehensive list of possible toxicities to a suggested drug to a patient, in this case, metformin. In order to give the physician a broad sense of the toxicities, we are providing not only the possible toxicities of metformin, but also of a drug similar to metformin. Here we are assuming that drugs with the same primary target and with the same interaction with this target, are similar and will have related toxicities. Thus, to give a broader sense of the toxicity of the drug, metformin, we are assuming that it can also have the the toxicity of its similar drug. Therefore to answer our question, we first need to find a drug that is similar to metformin by target and target mechanism (query 1), list the toxicities of both metformin and its similar drug (query 2).

Walk through the workflow: The following steps returns the toxicity and the similar drug to metformin.

The following legend is used to describe the instances of the classes.

Legend

The following classes from our ontology is used to answer the question.

Classes

The treatment document provides us with a drug that is suggested to our patient, Sam, based on his profile (details on how this answer was found is in the Recommendation competency question).

TreatmentDocument

The suggested drug is Metformin, and this is a subclass of both Biguanide and AMPKDrug in the Drug class. This is because the Drug class has classifications of drugs in two ways – one is function based (taken from the ADA guidelines), and the other is target based (taken from the Kyoto Encyclopedia of Genes and Genomes). The function based classification has all the antidiabetic drugs from the ADA guidelines, while the target based drugs can contain other drugs that have the same target as these drugs (this is where the similar drugs will be selected from). Now that we have our suggested drug, we need to find its primary target and target mechanism that is in relation to it.

Metformin

Thus, Metformin has the target AMPK, in the CAMKLFamily that is the gene that encodes this protein kinase, and it activates this target. Now that we need to find the similar drug to Metformin that has this same target and target mechanism. This is done by the following query:

Query 1: What is a similar drug to metformin by target and target mechanism?
This query has two possibilities, the first one simply finds the similar drug to metformin, while the second one creates a triple of :drug :hasSimilarDrug :drug that can be added back to our ontology.

Possibility 1

  1. prefix dbt: <https://tw.rpi.edu/Courses/Ontologies/2018/DiabetesTreatmentSupport/DiabetesTreatmentSupport/>
  2. prefix resource: <http://semanticscience.org/resource/>
  3. prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#>
  4. prefix sio: <http://semanticscience.org/resource/>
  5. prefix dct: <http://purl.org/dc/terms/>
  6.  
  7. SELECT ?drugLabel ?similarDrugLabel WHERE {
  8. ?drug rdf:type dbt:Biguanide ; rdfs:label ?drugLabel.
  9. ?drug dbt:hasPrimaryTarget ?target1 .
  10. ?drug dbt:hasTargetMechanism ?targetMechanism1 .
  11. ?similarDrug dbt:hasPrimaryTarget ?target1 ; dbt:hasTargetMechanism ?targetMechanism1 ; rdfs:label ?similarDrugLabel.
  12. FILTER ( ?drug != ?similarDrug )
  13. } LIMIT 50

Result

drugLabel similarDrugLabel
metformin phenformin

Possibility 2

  1. prefix dbt: <https://tw.rpi.edu/Courses/Ontologies/2018/DiabetesTreatmentSupport/DiabetesTreatmentSupport/>
  2. prefix resource: <http://semanticscience.org/resource/>
  3. prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#>
  4. prefix sio: <http://semanticscience.org/resource/>
  5. prefix dct: <http://purl.org/dc/terms/>
  6.  
  7. CONSTRUCT {
  8. ?drug dbt:hasSimilarDrug ?similarDrug .
  9. ?drug rdfs:label ?drugLabel .
  10. ?similarDrug rdfs:label ?similarDrugLabel .}
  11. WHERE {
  12. ?drug rdf:type dbt:Biguanide ; rdfs:label ?drugLabel.
  13. ?drug dbt:hasPrimaryTarget ?target1 .
  14. ?drug dbt:hasTargetMechanism ?targetMechanism1 .
  15. ?similarDrug dbt:hasPrimaryTarget ?target1 ; dbt:hasTargetMechanism ?targetMechanism1 ; rdfs:label ?similarDrugLabel.
  16. FILTER ( ?drug != ?similarDrug )
  17. } LIMIT 50
  18.  

Result

subject predicate object
metformin hasSimilarDrug phenformin

Now, we know that Phenfomin is a similar drug to Metformin, and this is an instance of AMPKDrug:

Instance

Now that we know the suggested drug (Metformin) and its similar drug by target and target mechanism (Phenformin), we can find the toxicities of both. First, the toxicity of Metformin is Vitamin B12 deficiency under Physical Adverse Event:

Metformin Toxicity

While for Phenformin the possible toxicities are, nausea and anorexia, also under the Physical Adverse Event:

Phenformin Toxicity

To access this information, we can carry out the following SPARQL query:

Query 2: What are the toxicities to Metformin and to drugs similar to Metformin?
Here we are listing the toxicities of both metformin and its similar drug, and with the query we also ensure that metformin is not listed as its own similar drug too.

  1. prefix dbt: <https://tw.rpi.edu/web/Courses/Ontologies/2018/OE_12_DiabetesTreatmentSupport/>
  2. prefix resource: <http://semanticscience.org/resource/>
  3. prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#>
  4. prefix sio: <http://semanticscience.org/resource/>
  5. prefix dct: <http://purl.org/dc/terms/>
  6.  
  7. SELECT ?drugLabel ?toxicityLabel ?similarDrugLabel ?toxicitySimilarLabel WHERE {
  8. ?drug rdf:type dbt:Biguanide ; rdfs:label ?drugLabel .
  9. ?drug dbt:hasToxicity ?toxicity .
  10. ?toxicity rdfs:label ?toxicityLabel.
  11. ?drug dbt:hasSimilarDrug ?similarDrug .
  12. ?similarDrug rdfs:label ?similarDrugLabel .
  13. ?similarDrug dbt:hasToxicity ?toxicitySimilar .
  14. ?toxicitySimilar rdfs:label ?toxicitySimilarLabel .
  15. }LIMIT 50

Result

drugLabel toxicityLabel similarDrugLabel toxicitySimilarLabel
metformin vitamin B12 deficiency phenformin anorexia
metformin vitamin B12 deficiency phenformin nausea

There is additional information on these toxicities available in our ontology, if needed. For instance, we have that these toxicities were found in humans:

Additional Information

Or if we wanted to know more about the specific research study these toxicities were found in, we could look in to the research study connected to them:

Connected Research Study

Here, focusing on the Vitamin B12 deficiency, the ontology contains information on its definition and the source of this definition, as well more information on the research study it was studied in. The deficiency was found in a clinical trial, and with annotations attached to this study, one can find more specific information on the clinical trial. This clinical trial also has a cohort connected to it, and this portion will be discussed in more detail in the Cohort section of our demonstration.

We do not present a SPARQL query for this portion, as only the first two queries are needed to answer the question of “what are the toxicities of metformin and a drug similar to metformin?”, but this portion provides more provenance to our answer, and is available in our ontology to be easily accessed by the object properties connected to each toxicity we list.

Click here to go back to Demonstration and Queries page

This was developed as a part of the Ontology Engineering course supervised by Prof. Deborah McGuinness and Ms. Elisa Kendall at RPI in Fall'18