Use Case C, Worflow 4

Workflow used to obtain data for the research paper ‘The application of the Open Pharmacological Concepts Triple Store (Open PHACTS) to support Drug Discovery Research’, currently submitted to PLOS ONE.  

Requirements:
- Knime v2.9
- Open PHACTS Knime nodes 1.0.0 (DON'T use any later version!): https://github.com/openphacts/OPS-Knime

Installation:
- Download "org.openphacts.utils.json_1.0.0.zip" and unzip it in the plugins folder of your KNIME installation
- Download the workflow (Use Case C_Workflow 4.zip)
- Start your Knime environment (you should see already a couple of new nodes at the ‘Node Repository’, like OPS_KNIME)
- Import the workflow (file>>import-workflow...>>select archive file)

Running:
- Double click on the desired workflow
- Reset the OPS nodes (in orange)
- Execute the nodes. Because of a bug found, the OPS nodes have to be run one by one to avoid the retrieved columns of the metanodes get mixed up.

Description of the Workflow:
1. We start with the text ‘regulation of Vitamin D’ and obtain GO terms associated by using ‘Free text to Concept’ API call. The output of the API was restricted to ‘alternative’ exact match type, to include only GO terms.
2. After removing duplicates and GO:0046137 (not specific of ‘Vitamind D’) we use GO terms urls as input for ‘Hierarchies: Child’ API call to retrieve Children of the GO terms.
3. The output from above is splitted into positive and negative regulators by using the ‘Row Filter’ node. After this we remove duplicates using the ‘GroupBy’ node and prepare the input for ‘Target Class Member: List’ API by renaming ‘Childnode’ to ‘uri’.
4. ‘Target Class Member: List’ API call is used to retrieve gene products associated with GO terms. Then we remove duplicates and keep only human genes using the ‘Nominal Value Row filter’ node.
5. In order to compare with proteins from the initial pathway (a table including all ‘Uniprot IDs’ from initial pathway need to be created manually), the string http://purl.uniprot.org/uniprot/  is removed by using the ‘String Replacer’ node.
6. Using the ‘Reference Row Filter’ node, we are able to show genes that are common to initial pathway and genes that are not from positive and negative regulators.