Recommendations to model data from Pathway Interaction Database in caBIO

Version 1

Release 4.2

Last Updated:

Owner: caBIO Team

Email: klemmj\@mail.nih.gov

National Cancer Institute Center for BioInformatics

6116 Executive Blvd.

Rockville, MD 20852

![](media/image1.png){width="1.5729166666666667in" height="1.03125in"}

1 Overview of PID Data and Proposed Object Model Changes 4

1.1 Description 4

1.2 Use Cases 4

1.2.1 Gene-Pathway Association 4

1.2.2 Protein-PathwayInteraction Association 5

1.2.3 Gene-PostTranslationalModification Association 6

1.2.4 Evidence-Gene Association 8

1.3 Proposed Object Model Changes 9

1.3.1 Existing Domain Model 9

1.3.2 Extended Domain Model 10

1.3.3 Existing Data and Associations 12

1.3.3.1.1 Observations 12

1.4 PID Dataset 12

1.4.1 Data Statistics 13

1.4.2 Doubts / Imponderables / Not Modeled 16

1.4.3 From Pathway Data to Proposed Model 16

1.4.4 From Interactions Data to Proposed Model 17

1.4.5 From Molecule Data to Proposed Model 19

2 Data Exemplars 21

2.1.1 Pathway Data 21

2.1.2 Interaction Data 21

2.1.3 Molecules Data 22

Overview of PID Data and Proposed Object Model Changes
======================================================

Description
-----------

The Pathway Interaction Database is a highly-structured, curated
collection of information about known biomolecular interactions and key
cellular processes assembled into signaling pathways. It is a
collaborative project between the US National Cancer Institute (NCI) and
Nature Publishing Group (NPG), and is an open access online resource. It
exposes data regarding pathways, complexcomponents and molecular
interactions from NCI-Nature-curated dataset, Reactome and BioCarta.

Use Cases
---------

### Gene-Pathway Association

![Use Case Model \_1.PNG](media/image2.png){width="6.572916666666667in"
height="1.4583333333333333in"}

+-----------------------+---------------------------------------------+
| **Use Case Name**     | **Gene-Pathway Association**                |
+=======================+=============================================+
| **Use Case ID**       | 2.1                                         |
+-----------------------+---------------------------------------------+
| **Primary Actor**     | Public                                      |
+-----------------------+---------------------------------------------+
| **Brief Description** | The *Gene-Pathway Association* use case     |
|                       | allows users to search for pathways         |
|                       | associated with a Gene. The results of high |
|                       | throughput data analysis, such microarray,  |
|                       | are often lists of genes that exhibit       |
|                       | certain behavior of interests to the        |
|                       | biologist, who wants to know whether any of |
|                       | these genes are associated with known       |
|                       | pthways in the literature.                  |
+-----------------------+---------------------------------------------+
| **Workflow**          | 1.  Query for caBIO Gene object by commonly |
|                       |     used IDs, such as HUGO symbol, or       |
|                       |     Genbank accession.                      |
|                       |                                             |
|                       | 2.  Get pathwayAssociations to retrieve     |
|                       |     associated pathways which in turn can   |
|                       |     be used to retrieve interactions, etc.  |
+-----------------------+---------------------------------------------+
| **Trigger**           | The user searches for a Gene                |
+-----------------------+---------------------------------------------+
| **Pre-conditions**    | 1.  The user navigates to the caBIO Home    |
|                       |     Page and clicks "Continue"              |
+-----------------------+---------------------------------------------+
| **Flow of Events**    | 1.  The user selects the Gene object        |
|                       |                                             |
|                       | 2.  The user provides a valid Gene Id such  |
|                       |     as a HUGO Symbol, etc                   |
|                       |                                             |
|                       | 3.  The user clicks the submit button to    |
|                       |     initiate the search                     |
|                       |                                             |
|                       | 4.  A list of Genes appear                  |
|                       |                                             |
|                       | 5.  The user can navigate to                |
|                       |     pathwayAssociations by clicking on the  |
|                       |     link, *getPathwayAssociation*.          |
+-----------------------+---------------------------------------------+
| **Post Conditions**   | *Success Condition:* The user successfully  |
|                       | searches the database and obtains a list of |
|                       | all pathways associated with a Gene         |
|                       |                                             |
|                       | *Alternate Condition:*                      |
|                       |                                             |
|                       | AC2: No result is found                     |
|                       |                                             |
|                       | *Error Conditions:*                         |
|                       |                                             |
|                       | EC1: System Error during Request Processing |
|                       |                                             |
|                       | EC2: Specified Gene does not exist          |
|                       |                                             |
|                       | EC3: Specified Association does not         |
|                       | identify a valid pathway                    |
+-----------------------+---------------------------------------------+
| **Alternative Flow**  | [Alternate Condition:]{.underline}          |
|                       |                                             |
|                       | AC2: No result is found                     |
|                       |                                             |
|                       | 1.  "No results found" message is displayed |
+-----------------------+---------------------------------------------+
| **Related Use Cases** | Protein-PathwayInteraction Associations,    |
|                       | Gene-PostTranslationalModification          |
|                       | Association, Evidence-Gene Association      |
+-----------------------+---------------------------------------------+
| **Issues/Notes**      | 1.  The user can also execute the same      |
|                       |     search using the Java API or Web        |
|                       |     Service                                 |
|                       |                                             |
|                       | 2.  This use case is already supported in   |
|                       |     caBIO 4.1, but with the introduction of |
|                       |     new datasets, additional data would be  |
|                       |     retrievable through this use-case       |
+-----------------------+---------------------------------------------+

### Protein-PathwayInteraction Association 

![Use Case Model\_3.PNG](media/image3.png){width="6.614583333333333in"
height="1.4583333333333333in"}

+-----------------------+---------------------------------------------+
| **Use Case Name**     | **Protein-PathwayInteraction Association**  |
+=======================+=============================================+
| **Use Case ID**       | 2.3                                         |
+-----------------------+---------------------------------------------+
| **Primary Actor**     | Public                                      |
+-----------------------+---------------------------------------------+
| **Brief Description** | The use case allows a user to retrieve      |
|                       | Pathway Interactions associated with a      |
|                       | given protein                               |
+-----------------------+---------------------------------------------+
| **Workflow**          | 1.  Search for a protein by its Uniprot Id. |
|                       |                                             |
|                       | 2.  Get PathwayCollection to retrieve       |
|                       |     associated pathways.                    |
|                       |                                             |
|                       | 3.  Click on interactionCollection to       |
|                       |     retrieve associated interactions.       |
|                       |                                             |
|                       | 4.  Filter by interaction type.             |
+-----------------------+---------------------------------------------+
| **Trigger**           | The user desires to search for Pathway      |
|                       | Interactions                                |
+-----------------------+---------------------------------------------+
| **Pre-conditions**    | The user navigates to the caBIO Home Page   |
|                       | and clicks "Continue"                       |
+-----------------------+---------------------------------------------+
| **Flow of Events**    | 1.  Click on Protein                        |
|                       |                                             |
|                       | 2.  Search for a Protein by its Uniprot Id  |
|                       |                                             |
|                       | 3.  Get Pathways by clicking on             |
|                       |     *getPathwayCollection*.                 |
|                       |                                             |
|                       | 4.  Click on *getInteractionCollection* to  |
|                       |     get associated interactions             |
+-----------------------+---------------------------------------------+
| **Post Conditions**   | *Success Condition:* The user successfully  |
|                       | searches the database and obtains a list of |
|                       | all interactions associated with the        |
|                       | pathways in which a given protein           |
|                       | participates                                |
|                       |                                             |
|                       | *Alternate Condition:*                      |
|                       |                                             |
|                       | AC2: No result is found                     |
|                       |                                             |
|                       | *Error Conditions:*                         |
|                       |                                             |
|                       | EC1: System Error during Request Processing |
|                       |                                             |
|                       | EC2: Specified Protein does not exist       |
|                       |                                             |
|                       | EC3: Specified Protein is not associated    |
|                       | with any Pathway                            |
+-----------------------+---------------------------------------------+
| **Alternative Flow**  | [Alternate Condition:]{.underline}          |
|                       |                                             |
|                       | AC2: No result is found                     |
|                       |                                             |
|                       | 1\. "No results found" message is displayed |
+-----------------------+---------------------------------------------+
| **Related Use Cases** | Gene-Pathway Associations,                  |
|                       | Gene-PostTranslationalModification          |
|                       | Association, Evidence-Gene Association      |
+-----------------------+---------------------------------------------+
| **Issues/Notes**      | The user can also execute the same search   |
|                       | using the Java API or Web Service           |
+-----------------------+---------------------------------------------+

### Gene-PostTranslationalModification Association

![Use Case Model\_4.PNG](media/image4.png){width="6.625in"
height="1.4583333333333333in"}

+-----------------------+---------------------------------------------+
| **Use Case Name**     | **Browse Gene-PostTranslationalModification |
|                       | Association**                               |
+=======================+=============================================+
| **Use Case ID**       | 2.4                                         |
+-----------------------+---------------------------------------------+
| **Primary Actor**     | Public                                      |
+-----------------------+---------------------------------------------+
| **Brief Description** | Given a gene, find all post translational   |
|                       | modifications associated with the expressed |
|                       | proteins on account of participation in a   |
|                       | pathway.                                    |
+-----------------------+---------------------------------------------+
| **Workflow**          | 1.  Start from a gene.                      |
|                       |                                             |
|                       | 2.  Get corresponding proteins.             |
|                       |                                             |
|                       | 3.  Get the post translational modification |
|                       |     information for the protein, if         |
|                       |     available.                              |
+-----------------------+---------------------------------------------+
| **Trigger**           | The user desires to search for publicly     |
|                       | available genes                             |
+-----------------------+---------------------------------------------+
| **Pre-conditions**    | 1.  The user navigates to the caBIO Home    |
|                       |     Page and clicks "Continue"              |
+-----------------------+---------------------------------------------+
| **Flow of Events**    | 1.  Click on Gene                           |
|                       |                                             |
|                       | 2.  Search for a Gene by its HUGO Symbol,   |
|                       |     Unigene Cluster Id, etc.                |
|                       |                                             |
|                       | 3.  Get expressed proteins by clicking on   |
|                       |     *getProtein*.                           |
|                       |                                             |
|                       | 4.  Click on                                |
|                       |     *getPostTranslationalModification* to   |
|                       |     get associated post translational       |
|                       |     modification information                |
+-----------------------+---------------------------------------------+
| **Post Conditions**   | *Success Condition:* The user successfully  |
|                       | searches the database and obtains a list of |
|                       | all available post translational            |
|                       | modification information for the expressed  |
|                       | gene.                                       |
|                       |                                             |
|                       | *Alternate Condition:*                      |
|                       |                                             |
|                       | AC2: No result is found                     |
|                       |                                             |
|                       | *Error Conditions:*                         |
|                       |                                             |
|                       | EC1: System Error during Request Processing |
|                       |                                             |
|                       | EC2: Specified Protein does not exist       |
|                       |                                             |
|                       | EC3: Specified Protein has not undergone    |
|                       | any post translational modification or has  |
|                       | not participated in any pathways stored in  |
|                       | caBIO                                       |
+-----------------------+---------------------------------------------+
| **Alternative Flow**  | [Alternate Condition:]{.underline}          |
|                       |                                             |
|                       | AC2: No result is found                     |
|                       |                                             |
|                       | 1\. "No results found" message is displayed |
+-----------------------+---------------------------------------------+
| **Related Use Cases** | Gene-Pathway Association,                   |
|                       | Protein-PathwayInteraction Association,     |
|                       | Evidence-Gene Association                   |
+-----------------------+---------------------------------------------+
| **Issues/Notes**      | The user can also execute the same search   |
|                       | using the Java API or Web Service           |
+-----------------------+---------------------------------------------+

### Evidence-Gene Association

![Use Case Model\_5.PNG](media/image5.png){width="6.572916666666667in"
height="1.4583333333333333in"}

+-----------------------+---------------------------------------------+
| **Use Case Name**     | **Browse Evidence-Pathway Association**     |
+=======================+=============================================+
| **Use Case ID**       | 2.4                                         |
+-----------------------+---------------------------------------------+
| **Primary Actor**     | Public                                      |
+-----------------------+---------------------------------------------+
| **Brief Description** | Given a publication which documents a       |
|                       | particular pathway interaction, find all    |
|                       | genes associated with the same.             |
+-----------------------+---------------------------------------------+
| **Workflow**          | 1.  Start from a publication/Evidence       |
|                       |     retrievable using its PubMed Id.        |
|                       |                                             |
|                       | 2.  Get corresponding Pathway Interactions. |
|                       |                                             |
|                       | 3.  Get associated Pathways                 |
|                       |                                             |
|                       | 4.  Get associated Genes                    |
+-----------------------+---------------------------------------------+
| **Trigger**           | The user desires to search for publication  |
|                       | information                                 |
+-----------------------+---------------------------------------------+
| **Pre-conditions**    | 1.  The user navigates to the caBIO Home    |
|                       |     Page and clicks "Continue"              |
+-----------------------+---------------------------------------------+
| **Flow of Events**    | 1.  Click on Evidence                       |
|                       |                                             |
|                       | 2.  Search for a Evidence using its PubMed  |
|                       |     Id                                      |
|                       |                                             |
|                       | 3.  Get associated PathwayInteractions.     |
|                       |                                             |
|                       | 4.  Click on *getPathwayCollection* to get  |
|                       |     associated pathways                     |
|                       |                                             |
|                       | 5.  Click on *getGene* to get associated    |
|                       |     Genes                                   |
+-----------------------+---------------------------------------------+
| **Post Conditions**   | *Success Condition:* The user successfully  |
|                       | searches the database and obtains a list of |
|                       | all genes associated with a given           |
|                       | publication on account of the pathways and  |
|                       | the interactions it is involved in          |
|                       |                                             |
|                       | *Alternate Condition:*                      |
|                       |                                             |
|                       | AC2: No result is found                     |
|                       |                                             |
|                       | *Error Conditions:*                         |
|                       |                                             |
|                       | EC1: System Error during Request Processing |
|                       |                                             |
|                       | EC2: Specified Publication does not exist   |
|                       |                                             |
|                       | EC3: Specified Publication is not           |
|                       | associated with any PathwayInteraction      |
+-----------------------+---------------------------------------------+
| **Alternative Flow**  | [Alternate Condition:]{.underline}          |
|                       |                                             |
|                       | AC2: No result is found                     |
|                       |                                             |
|                       | 1\. "No results found" message is displayed |
+-----------------------+---------------------------------------------+
| **Related Use Cases** | Gene-Pathway Association,                   |
|                       | Protein-PathwayInteraction Association,     |
|                       | Gene-PostTranslationalModification          |
+-----------------------+---------------------------------------------+
| **Issues/Notes**      | The user can also execute the same search   |
|                       | using the Java API or Web Service           |
+-----------------------+---------------------------------------------+

Proposed Object Model Changes
-----------------------------

### Existing Domain Model

The follow objects from the current caBIO domain model are relevant to
the modeling this data in caBIO.

Figure 1 describes the current caBIO model that associates these
objects.

+---------------------------+-----------------------------------------+
| ***caBIO Domain Object*** |                                         |
+===========================+=========================================+
| Pathway                   | An object representation of a           |
|                           | molecular/cellular pathway in human and |
|                           | mouse compiled by BioCarta. It provides |
|                           | access to further details about the     |
|                           | associated Genes and any available      |
|                           | histopathological information for genes |
|                           | involved in clinical trials through     |
|                           | getGeneCollection and                   |
|                           | getHistopathologyCollection methods.    |
|                           |                                         |
|                           | It gets populated with data from CGAP   |
|                           | and is composed of BioCarta Pathways.   |
|                           | It provides links to genes associated   |
|                           | with every pathway as well as           |
|                           | histopathological information           |
|                           | pertaining to these Genes through the   |
|                           | associated Histopathology object.       |
+---------------------------+-----------------------------------------+
| NucleicAcidSequence       | An object representation of a gene      |
|                           | sequence; provides access to the clones |
|                           | from which it was derived, the ASCII    |
|                           | representation of the residues it       |
|                           | contains, and the sequence ID and a     |
|                           | link to the Location Objects that in    |
|                           | turn provide further details of any     |
|                           | SNP, Cytoband, EST or MRNAs associated  |
|                           | with that sequence.                     |
|                           |                                         |
|                           | It is populated with data pertaining to |
|                           | human and mouse from Unigene.           |
+---------------------------+-----------------------------------------+
| Gene                      | Gene objects are the effective portal   |
|                           | to most of the genomic information      |
|                           | provided by the caBIO data services; It |
|                           | provides access to the associated       |
|                           | proteins, gene-targets, diseases,       |
|                           | histopathologies, ontologies, pathways, |
|                           | aliases, clones and sequence data       |
|                           | through their respective objects such   |
|                           | as Histopathology, DiseaseOntology,     |
|                           | OrganOntology, Pathway, GeneAlias,      |
|                           | Clone and NucleicAcidSequence           |
|                           | respectively.                           |
|                           |                                         |
|                           | The location of the gene on the         |
|                           | chromosome is available through the     |
|                           | Location object.                        |
|                           |                                         |
|                           | This object gets populated with data    |
|                           | pertaining to human and mouse genes     |
|                           | from NCBI's Unigene's repository. Gene  |
|                           | Ids from NCBI's OMIM Databank, Ensembl, |
|                           | and Enzyme Commission are available     |
|                           | through DatabaseCrossReference.         |
+---------------------------+-----------------------------------------+
| Protein                   | An object representing the various      |
|                           | names (scientific, common, abbreviated, |
|                           | etc.) for human and mouse genomes. It   |
|                           | can be used to retrieve the associated  |
|                           | Genes, Chromosomes, Pathways if any,    |
|                           | Proteins, or Tissues.                   |
+---------------------------+-----------------------------------------+
| **Evidence**              | An object representing the publication  |
|                           | from PubMed that serves as an Evidence  |
|                           | supporting the association between a    |
|                           | caBIO Gene and a DiseaseOntology or an  |
|                           | Agent. Based on the publication, an     |
|                           | Evidence can be associated with         |
|                           | multiple EvidenceCodes.                 |
+---------------------------+-----------------------------------------+
| **EvidenceCode**          | A class that models the different types |
|                           | of EvidenceCodes associated with an     |
|                           | Evidence, based on the data in the      |
|                           | publication.                            |
+---------------------------+-----------------------------------------+

![](media/image6.png){width="6.5in" height="5.791666666666667in"}

Figure Current caBIO Model

### Extended Domain Model 

The extended model adds supports for new objects to model the
pathwayInteractions, the different components in an interaction and its
association to an Evidence or EvidenceCode.

![](media/image7.png){width="6.5in" height="6.427083333333333in"}

Figure Proposed Model for Pathway Data Modeling

Note: New classes or attributes are highlighted in red

**Pathway**

New attributes would be added to model the curator, reviewer and source
information

  **Attribute**   **Description**
  --------------- -------------------------------------------------
  Diagram         Pathway Diagram in SVG Format
  Description     Sentence from PubMed publication
  Name            Short name for the pathway
  LongName        Long name for the pathway
  DisplayValue    Display value for the diagram
  CuratorList     List of curators
  ReviewerList    List of reviewers
  Source          Pathway Source (Reactome, BioCarta, NCI-Nature)

**PathwayInteraction**

New class to model the interactions that constitute a Pathway

  **Attribute**   **Description**
  --------------- -------------------------------------
  Role            Role of an interaction in a Pathway

**PostTranslationalModification**

New class to model the Post Translational Modification information for a
protein where available

  **Attribute**   **Description**
  --------------- ---------------------------------------------
  Aa              Amino acid
  Position        Position at which modification has occurred
  Modification    Type of modification

### Existing Data and Associations

Currently caBIO procures BioCarta data from CMAP which gives a Locus
Link Id that allows us to associate a caBIO Gene with a Pathway.

This would need to be retained for backward compatibility since caMOD
and Rembrandt amongst others use this data.

##### Observations 

1.  Retain existing data and associations (316 pathways currently in
    caBIO)

2.  Set PathwaySource as 'BioCarta' for existing data (254 pathways from
    PID datasets)

    1.  244 of these 254 pathways are already present in caBIO

3.  Add data to model associations to Proteins and Interactions for the
    human pathways from these 244 records

4.  Add remaining 10 pathways

5.  Outcome:

    1.  244 Pathways would have an association to Gene AND Protein and
        Interaction

    2.  Mouse Pathways in caBIO\'s Pathway will have no association to
        PathwayInteractions; Only the Human Pathways will.

    3.  10 newly added Pathways will have no association to Gene, but
        will have an association to PathwayInteractions.

    4.  Resulting total number of BioCarta pathways : 316 + 10 = 317

PID Dataset
-----------

Based on the above model, the tables below summarize the data available
from the PID dataset and their proposed association to caBIO.

According to the DTD, a *Pathway* is composed of one or more
*PathwayInteractions*, and has associated *Evidences*.

It is composed of multiple *PathwayInteractions* which play one of 227
roles in the *Pathway*.

Every *PathwayInteraction* also has associated *Evidences* or
*EvidenceCodes*.

A *PathwayInteractionCondition* influences a *PathwayInteraction*

Multiple *PathwayInteractionComponents* (Molecules) participate in a
*PathwayInteraction* with each Component being defined by its role in
the Interaction. Every *Molecule* can function as either as an input,
output, agent or inhibitor in a *PathwayInteraction*. There are some
records with "process-type" as the role which would be pruned as junk
data

However there may be many different aspects to each such role which is
modeled by *PathwayInteractionComponentLabel.*

These molecules are identified by aliases or Uniprot accession numbers
or descriptions in some cases.

Some Proteins have subunit information available and it may be these
subunits that may participate in a Pathway.

It may also be "collections" of Complex/Compounds/Proteins that
participate in a PathwayInteraction.

### Data Statistics

+----------------------+----------------------+----------------------+
| **Pathways**         | **Description**      | **Notes**            |
+======================+======================+======================+
| ZSTG\_PATHWAYS       | Pathway Data         | Reactome: 765        |
|                      | (consists of the     |                      |
|                      | source, long/short   | NCI-Nature: 111      |
|                      | name, organism)      |                      |
|                      |                      | Source Id No. 3: 154 |
|                      | PID uses "7" to      | *(presumably "3"     |
|                      | refer to Reactome    | also refers to       |
|                      | and "5" to           | BioCarta)???*        |
|                      | NCI-Nature           |                      |
|                      |                      | BioCarta: 101        |
|                      | Only Human Data      |                      |
|                      | available. Hence     |                      |
|                      | organism = Hs for    |                      |
|                      | all records          |                      |
+----------------------+----------------------+----------------------+
| Z                    | A Pathway can be     | **Pathway Curators** |
| STG\_PATHWAYCURATORS | curated/ reviewed by |                      |
| /                    | multiple people      | Reactome: 656        |
| ZS                   |                      |                      |
| TG\_PATHWAYREVIEWERS |                      | NCI-Nature: 106      |
|                      |                      |                      |
|                      |                      | BioCarta: 0          |
|                      |                      |                      |
|                      |                      | **Pathway            |
|                      |                      | Reviewers**          |
|                      |                      |                      |
|                      |                      | Reactome: 7          |
|                      |                      |                      |
|                      |                      | NCI-Nature: 224      |
|                      |                      |                      |
|                      |                      | BioCarta: 0          |
+----------------------+----------------------+----------------------+
| ZST                  | Gives the            | Reactome: 3219       |
| G\_PATHWAYCOMPONENTS | Interaction Ids      |                      |
|                      | associated with a    | NCI-Nature: 4095     |
|                      | Pathway              |                      |
|                      |                      | BioCarta: 1557       |
|                      |                      |                      |
|                      |                      | Source Id No.3: 2227 |
+----------------------+----------------------+----------------------+
|                      |                      | *DTD implies a       |
|                      |                      | 1-to-many            |
|                      |                      | association between  |
|                      |                      | Pathway and          |
|                      |                      | Reference/Evidence,  |
|                      |                      | but there is no data |
|                      |                      | to support this.*    |
|                      |                      |                      |
|                      |                      | *All References are  |
|                      |                      | associated only with |
|                      |                      | an Interaction and   |
|                      |                      | not with a Pathway.* |
+----------------------+----------------------+----------------------+
|                      |                      |                      |
+----------------------+----------------------+----------------------+
| **Interactions**     |                      |                      |
+----------------------+----------------------+----------------------+
| ZSTG\_INTERACTIONS   | Lists the            | Reactome: 3020       |
|                      | interactions in each |                      |
|                      | Pathway              | NCI-Nature: 3941     |
|                      |                      |                      |
|                      |                      | BioCarta: 1759       |
|                      |                      |                      |
|                      |                      | 2: 1244              |
+----------------------+----------------------+----------------------+
| ZSTG\                | Lists the multiple   | Reactome: 3020       |
| _INTERACTIONEVIDENCE | evidence-Codes       |                      |
|                      | associated with each | NCI-Nature: 5468     |
|                      | Interaction          |                      |
|                      |                      | "3": 1759            |
|                      |                      |                      |
|                      |                      | BioCarta: 1244       |
+----------------------+----------------------+----------------------+
| ZSTG\_               | Lists the multiple   | Reactome: 3922       |
| INTERACTIONREFERENCE | publications         |                      |
|                      | associated with each | NCI-Nature: 4956     |
|                      | Interaction          |                      |
|                      |                      | BioCarta: 0          |
|                      |                      |                      |
|                      |                      | 3: 0                 |
+----------------------+----------------------+----------------------+
| ZSTG\_               | Lists the multiple   | Reactome: No data    |
| INTERACTIONCONDITION | conditions           |                      |
|                      | associated with each | NCI Nature: 250      |
|                      | Pathway Interaction  |                      |
|                      |                      | 3: 50                |
|                      |                      |                      |
|                      |                      | BioCarta: 70         |
|                      |                      |                      |
|                      |                      | *DTD implies a       |
|                      |                      | 1-to-many            |
|                      |                      | association, but PID |
|                      |                      | data shows a 1-to-1  |
|                      |                      | association between  |
|                      |                      | PathwayInteraction   |
|                      |                      | and                  |
|                      |                      | PathwayIn            |
|                      |                      | teractionCondition.* |
|                      |                      |                      |
|                      |                      | *On the basis of     |
|                      |                      | this "condition"     |
|                      |                      | could be modeled     |
|                      |                      | simply as an         |
|                      |                      | attribute of         |
|                      |                      | Interaction*         |
+----------------------+----------------------+----------------------+
|                      |                      |                      |
+----------------------+----------------------+----------------------+
| ZSTG\_INTER          | Lists the different  | What is the          |
| ACTIONCOMPONENTLABEL | molecules            | difference between   |
|                      | participating in     | Role-Type and        |
|                      | each Interaction     | Label-Type? All      |
|                      | along with their     | I                    |
|                      | roles (agent,        | nteractionComponents |
|                      | inhibitor, input,    | have only one role,  |
|                      | output) and the 5    | but many have        |
|                      | different            | multiple Component   |
|                      | lable-types(i.e.     | Labels.              |
|                      | activity-state,      |                      |
|                      | location, function,  | N                    |
|                      | ptm)                 | CI-Nature:agent:1593 |
|                      |                      |                      |
|                      |                      | Reactome:agent:3048  |
|                      |                      |                      |
|                      |                      | 3:agent:967          |
|                      |                      |                      |
|                      |                      | BioCarta:agent: 662  |
|                      |                      |                      |
|                      |                      | NC                   |
|                      |                      | I-Nature:inhibitor:2 |
|                      |                      |                      |
|                      |                      | Re                   |
|                      |                      | actome:inhibitor:346 |
|                      |                      |                      |
|                      |                      | 3:inhibitor:128      |
|                      |                      |                      |
|                      |                      | B                    |
|                      |                      | ioCarta:inhibitor:14 |
|                      |                      |                      |
|                      |                      | N                    |
|                      |                      | CI-Nature:input:6253 |
|                      |                      |                      |
|                      |                      | Reactome:input:3361  |
|                      |                      |                      |
|                      |                      | 3:input:1116         |
|                      |                      |                      |
|                      |                      | BioCarta:input:484   |
|                      |                      |                      |
|                      |                      | NC                   |
|                      |                      | I-Nature:output:5540 |
|                      |                      |                      |
|                      |                      | Reactome:output:3795 |
|                      |                      |                      |
|                      |                      | 2:output:1366        |
|                      |                      |                      |
|                      |                      | BioCarta:output: 934 |
|                      |                      |                      |
|                      |                      | **Label-types for    |
|                      |                      | the different        |
|                      |                      | Int                  |
|                      |                      | eractionComponents** |
|                      |                      | (activity-state,     |
|                      |                      | location, function,  |
|                      |                      | ptm)                 |
|                      |                      |                      |
|                      |                      | BioCarta             |
|                      |                      | :activity-state:1266 |
|                      |                      |                      |
|                      |                      | B                    |
|                      |                      | ioCarta:location:828 |
|                      |                      |                      |
|                      |                      | 3                    |
|                      |                      | :activity-state:1308 |
|                      |                      |                      |
|                      |                      | 3:location:2269      |
|                      |                      |                      |
|                      |                      | NCINature            |
|                      |                      | :activity-state:4972 |
|                      |                      |                      |
|                      |                      | N                    |
|                      |                      | CINature:function:43 |
|                      |                      |                      |
|                      |                      | NCI                  |
|                      |                      | Nature:location:5535 |
|                      |                      |                      |
|                      |                      | Reactom              |
|                      |                      | e:activity-state:145 |
|                      |                      |                      |
|                      |                      | Rea                  |
|                      |                      | ctome:location:13237 |
|                      |                      |                      |
|                      |                      | Rea                  |
|                      |                      | ctome:process-type:5 |
|                      |                      |                      |
|                      |                      | Reactome:ptm:1       |
+----------------------+----------------------+----------------------+
| ZSTG\_INTER          | An Interaction       | Reactome:1183        |
| ACTIONCOMP-PTM-TERMS | involves multiple    |                      |
|                      | c                    | NCINature:2862       |
|                      | omponents/molecules, |                      |
|                      | each identified by a | BioCarta: 0          |
|                      | moleculeId (which is |                      |
|                      | used to provide      | Source No "3": 0     |
|                      | further information  |                      |
|                      | on the molecule) and |                      |
|                      | each playing a       |                      |
|                      | different role in    |                      |
|                      | the Interaction.     |                      |
|                      | Some of these have   |                      |
|                      | associated           |                      |
|                      | PostTrans            |                      |
|                      | lationalModification |                      |
|                      | (PTM) data           |                      |
|                      |                      |                      |
|                      | Lists the PTM data   |                      |
|                      | for these molecules, |                      |
|                      | if available         |                      |
+----------------------+----------------------+----------------------+
|                      |                      |                      |
+----------------------+----------------------+----------------------+
| **Molecules**        |                      |                      |
+----------------------+----------------------+----------------------+
| ZSTG\_MOLECULENAMES  | Lists the type of    | There is             |
|                      | molecule and the     | insufficient data to |
|                      | value (an            | create a separate    |
|                      | iden                 | Complex or Compound  |
|                      | tifier/description). | object. The "value"  |
|                      | There are only 5     | column of this table |
|                      | types of molecules   | is composed of       |
|                      | in the data:         | comments/aliases/    |
|                      | complex, compound,   | descriptions/symbols |
|                      | protein, and rna.    | and is the only new  |
|                      |                      | data/attribute that  |
|                      | Records of type      | could added to this  |
|                      | "molecule-type"      | new object.          |
|                      | would be purged      |                      |
|                      |                      | Almost all the       |
|                      | NC                   | entries for "rna"    |
|                      | INature:complex:1870 | molecules are        |
|                      |                      | comments and some    |
|                      | NC                   | "protein" molecules  |
|                      | INature:compound:201 | have accession       |
|                      |                      | numbers.             |
|                      | NC                   |                      |
|                      | INature:protein:4121 | *Approximately only  |
|                      |                      | 3000-4000 of the     |
|                      | NCINature:rna:7      | 33,000+ molecules is |
|                      |                      | associated with      |
|                      | R                    | caBIO Identifiers.*  |
|                      | eactome:complex:3332 |                      |
|                      |                      |                      |
|                      | Re                   |                      |
|                      | actome:compound:2613 |                      |
|                      |                      |                      |
|                      | Reacto               |                      |
|                      | me:molecule-type:754 |                      |
|                      |                      |                      |
|                      | Reactome:protein:    |                      |
|                      | 7624                 |                      |
|                      |                      |                      |
|                      | Reactome:rna:67      |                      |
|                      |                      |                      |
|                      | (null):complex:884   |                      |
|                      |                      |                      |
|                      | (null):compound:644  |                      |
|                      |                      |                      |
|                      | (null):protein:7268  |                      |
|                      |                      |                      |
|                      | (null):rna:14        |                      |
+----------------------+----------------------+----------------------+
| ZSTG\_MO             | Only some "complex"  | Reactome:1691        |
| LECULE-COMP-PTMTERMS | Molecules have PTM   |                      |
|                      | data associated with | NCINature:4609       |
|                      | them. (6300)         |                      |
+----------------------+----------------------+----------------------+
| ZSTG\_MOLECULEPARTS  | Subunits of          | NCINature: 194       |
|                      | "protein" molecules  |                      |
|                      |                      | Reactome: 549        |
|                      |                      |                      |
|                      |                      | Null Source Id: 68   |
|                      |                      | (from BioCarta       |
|                      |                      | file..hence possibly |
|                      |                      | BioCarta??)          |
+----------------------+----------------------+----------------------+
| ZS                   | Molecules of type    | NCI Nature: 738      |
| TG\_MOLECULEFAMILIES | "protein", "complex" |                      |
|                      | and "compound" have  | Null: 1408           |
|                      | family-data          |                      |
|                      | associated with them |                      |
+----------------------+----------------------+----------------------+

### Doubts / Imponderables / Not Modeled

1.  Complex

2.  Compound

3.  Would be classes with one attribute

4.  Little to no associations to existing caBIO Protein(?) objects based
    > on (10)

5.  PathwayInteractionComponent's role (Role of a molecule participating
    > in a PathwayInteraction)

6.  PathwayInteractionComponentLabel (Additional information on the role
    > of the molecule in a pathway interaction)

7.  ProteinSubUnit Information

8.  Family information where available (Complexes being collections of
    > other complexes, etc)

9.  No data to warrant association between Pathway and Evidence.

10. *Insufficient information to map caBIO Ids on most of the
    > participating molecules in the Pathway Data*

### From Pathway Data to Proposed Model 

  **Data**                                               **Model**                                                    **Notes**
  ------------------------------------------------------ ------------------------------------------------------------ -----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
  \<Pathway id=\"500317\" subnet=\"true\"\>              **Pathway**                                                  
  \<Organism\>Hs\</Organism\>                            Used to make association to Taxon (Humans)                   
  \<LongName\>Signalling to RAS\</LongName\>             **Pathway**.name                                             
  \<ShortName\>Signalling\_to\_RAS\</ShortName\>         **Pathway**.shortName                                        
  \<Source id=\"7\"\>Reactome\</Source\>                 **Pathway**.source                                           
  \<CuratorList\>                                                                                                     
  \<Curator\>Nasi, S, Annibali, D\</Curator\>            **Pathway**.curatorList                                      Concatenate all curators into a single record
  \<Curator\>Jassal, B\</Curator\>                                                                                    
  \</CuratorList\>                                                                                                    
  \<ReviewerList\>                                                                                                    
  \<Reviewer\>Greene, LA\</Reviewer\>                    **Pathway**.reviewerList                                     Concatenate all reviewers into a single record
  \<Reviewer\>Dr. Dan Dumont\</Reviewer\>                                                                             
  \<Reviewer\>Dr. Andreas Papapetropoulos\</Reviewer\>                                                                
  \</ReviewerList\>                                                                                                   Neither Reactome nor NCI Nature datasets have any data to support association between **Pathway and Evidence**; Data exists to support only the association between Interaction and Evidence.
  \<PathwayComponentList\>                                                                                            
  \<PathwayComponent interaction\_idref=\"500704\"/\>    To make appropriate association to **PathwayInteractions**   
  \<PathwayComponent interaction\_idref=\"501216\"/\>                                                                 
  \<PathwayComponent interaction\_idref=\"503170\"/\>                                                                 
  \<PathwayComponent interaction\_idref=\"500703\"/\>                                                                 
  \<PathwayComponent interaction\_idref=\"501218\"/\>                                                                 
  \<PathwayComponent interaction\_idref=\"501217\"/\>                                                                 
  \<PathwayComponent interaction\_idref=\"503168\"/\>                                                                 
  \<PathwayComponent interaction\_idref=\"503522\"/\>                                                                 
  \</PathwayComponentList\>                                                                                           
  \</Pathway\>                                                                                                        

###  {#section .list-paragraph}

### From Interactions Data to Proposed Model

+----------------------+----------------------+----------------------+
| **Data**             | **Model**            | **Notes**            |
+======================+======================+======================+
| \<Interaction        | PathwayInteracti     | 227 different        |
| interaction\_t       | on.interaction\_type | interaction types.   |
| ype=\"modification\" |                      |                      |
| id=\"500460\"\>      | Id: used to make an  | Unclear about        |
|                      | association between  |                      |
|                      | **Pathway** and      | **Pathway** is       |
|                      | **                   | associated with      |
|                      | PathwayInteraction** | multiple             |
|                      |                      | **P                  |
|                      |                      | athwayInteractions** |
+----------------------+----------------------+----------------------+
| \<Condition          | **PathwayInteracti   | DTD shows 1-to-many  |
| conditio             | on.**condition\_type | association between  |
| n\_type=\"retrograde |                      | Interaction and      |
| axon cargo           |                      | Condition            |
| tra                  |                      | (hypothetical        |
| nsport\"\>retrograde |                      | example shown        |
| a                    |                      | alongside).          |
|                      |                      |                      |
| xon cargo            |                      | However data shows   |
| tra                  |                      | only one condition   |
| nsport\</Condition\> |                      | for every            |
|                      |                      | interaction.         |
|                      |                      |                      |
|                      |                      | Hence                |
|                      |                      | condition\_type      |
|                      |                      | could be attribute   |
|                      |                      | of                   |
|                      |                      | **                   |
|                      |                      | PathwayInteraction** |
+----------------------+----------------------+----------------------+
| \<Condition          |                      |                      |
| condition\_type=\"B- |                      |                      |
| Lymphocyte\"\>B-Lymp |                      |                      |
| hocyte\</Condition\> |                      |                      |
+----------------------+----------------------+----------------------+
| \<Condition          |                      |                      |
| conditio             |                      |                      |
| n\_type=\"activation |                      |                      |
| of NF-kappaB         |                      |                      |
| transcription        |                      |                      |
| factor\"\>activation |                      |                      |
| of NF-kappaB         |                      |                      |
| transcription        |                      |                      |
| factor\</Condition\> |                      |                      |
+----------------------+----------------------+----------------------+
| \<Abstraction        |                      | This information is  |
| pathw                |                      | already captured in  |
| ay\_idref=\"500682\" |                      | **Pathway**          |
| pathway\_name=\"Orc1 |                      |                      |
| removal from         |                      |                      |
| chromatin\"          |                      |                      |
| external\_pathway\_  |                      |                      |
| id=\"Orc1\_removal\_ |                      |                      |
| from\_chromatin\"/\> |                      |                      |
+----------------------+----------------------+----------------------+
| \<Source             | Used to make         |                      |
| id=\"7\"\            | associations to      |                      |
| >Reactome\</Source\> | **Pathways** from    |                      |
|                      | appropriate source   |                      |
+----------------------+----------------------+----------------------+
| \<EvidenceList\>     |                      |                      |
+----------------------+----------------------+----------------------+
| \<Evidence           | **Evidenc            |                      |
| value=\"NIL          | eCode**.evidenceCode |                      |
| \"\>NIL\</Evidence\> |                      |                      |
+----------------------+----------------------+----------------------+
| \</EvidenceList\>    |                      |                      |
+----------------------+----------------------+----------------------+
| \<ReferenceList\>    |                      |                      |
+----------------------+----------------------+----------------------+
| \<Reference          | *                    |                      |
| p                    | *Evidence**.pubmedId |                      |
| mid=\"16612002\"\>16 |                      |                      |
| 612002\</Reference\> |                      |                      |
+----------------------+----------------------+----------------------+
| \<Reference          |                      |                      |
| pmid=\"9687533\"\>9  |                      |                      |
| 687533\</Reference\> |                      |                      |
+----------------------+----------------------+----------------------+
| \<Reference          |                      |                      |
| p                    |                      |                      |
| mid=\"12660731\"\>12 |                      |                      |
| 660731\</Reference\> |                      |                      |
+----------------------+----------------------+----------------------+
| \</ReferenceList\>   |                      |                      |
+----------------------+----------------------+----------------------+
| \<Intera             | Not modeled          | **                   |
| ctionComponentList\> |                      | PathwayInteraction** |
|                      |                      | is composed of many  |
|                      |                      | PathwayI             |
|                      |                      | nteractionComponents |
+----------------------+----------------------+----------------------+
| \<                   | Not modeled          | 4 different roles    |
| InteractionComponent |                      | for a                |
| role\_type=\"input\" |                      | **PathwayInt         |
| molecule             |                      | eractionComponent**: |
| \_idref=\"501651\"\> |                      | 4 (input, output,    |
|                      |                      | inhibitor, agent)    |
+----------------------+----------------------+----------------------+
| \<Label              | Not modeled          | Data from NCI Nature |
| labe                 |                      | shows 1-to-many      |
| l\_type=\"location\" |                      | association between  |
| va                   |                      | **PathwayIn          |
| lue=\"cytoplasm\"/\> |                      | teractionComponent** |
|                      |                      | and                  |
|                      |                      | **PathwayInterac     |
|                      |                      | tionComponentLabel** |
|                      |                      |                      |
|                      |                      | 5 different          |
|                      |                      | label-types:         |
|                      |                      | Activity-state,      |
|                      |                      | function, ptm,       |
|                      |                      | location,            |
|                      |                      | process-type         |
|                      |                      |                      |
|                      |                      | 96 different         |
|                      |                      | Label-values         |
+----------------------+----------------------+----------------------+
| \<Label              |                      |                      |
| label\_typ           |                      |                      |
| e=\"activity-state\" |                      |                      |
| value=\"active\"/\>  |                      |                      |
+----------------------+----------------------+----------------------+
| \</In                |                      |                      |
| teractionComponent\> |                      |                      |
+----------------------+----------------------+----------------------+
| \<                   |                      |                      |
| InteractionComponent |                      |                      |
| role\_type=\"input\" |                      |                      |
| molecule             |                      |                      |
| \_idref=\"505232\"\> |                      |                      |
+----------------------+----------------------+----------------------+
| \<Label              | Not Modeled          |                      |
| labe                 |                      |                      |
| l\_type=\"location\" |                      |                      |
| value=\"plasma       |                      |                      |
| membrane\"/\>        |                      |                      |
+----------------------+----------------------+----------------------+
| \<PTMExpression\>    | **PostTransla        | Would have           |
|                      | tionalModification** | many-to-one          |
|                      |                      | association with     |
|                      |                      | Protein              |
+----------------------+----------------------+----------------------+
| \<PTMTerm            | Protein accession    |                      |
| protein=\"Q6PIZ9\"   | number would be used |                      |
| position=\"63\"      | to make association  |                      |
| aa=\"Y\"             | with caBIO Protein   |                      |
| modification=\"      |                      |                      |
| phosphorylation\"/\> | **                   |                      |
|                      | PostTranslationalMod |                      |
|                      | ification**.position |                      |
|                      |                      |                      |
|                      | **PostTranslatio     |                      |
|                      | nalModification**.aa |                      |
|                      |                      |                      |
|                      | **Post               |                      |
|                      | TranslationalModific |                      |
|                      | ation**.modification |                      |
+----------------------+----------------------+----------------------+
| \<PTMTerm            |                      |                      |
| protein=\"Q6PIZ9\"   |                      |                      |
| position=\"79\"      |                      |                      |
| aa=\"Y\"             |                      |                      |
| modification=\"      |                      |                      |
| phosphorylation\"/\> |                      |                      |
+----------------------+----------------------+----------------------+
| \<PTMTerm            |                      |                      |
| protein=\"Q6PIZ9\"   |                      |                      |
| position=\"110\"     |                      |                      |
| aa=\"Y\"             |                      |                      |
| modification=\"      |                      |                      |
| phosphorylation\"/\> |                      |                      |
+----------------------+----------------------+----------------------+
| \</PTMExpression\>   |                      |                      |
+----------------------+----------------------+----------------------+
| \</In                |                      |                      |
| teractionComponent\> |                      |                      |
+----------------------+----------------------+----------------------+
| \<                   |                      |                      |
| InteractionComponent |                      |                      |
| r                    |                      |                      |
| ole\_type=\"output\" |                      |                      |
| molecule             |                      |                      |
| \_idref=\"501654\"\> |                      |                      |
+----------------------+----------------------+----------------------+
| \<Label              |                      |                      |
| labe                 |                      |                      |
| l\_type=\"location\" |                      |                      |
| value=\"plasma       |                      |                      |
| membrane\"/\>        |                      |                      |
+----------------------+----------------------+----------------------+
| \</In                |                      |                      |
| teractionComponent\> |                      |                      |
+----------------------+----------------------+----------------------+
| \</Intera            |                      |                      |
| ctionComponentList\> |                      |                      |
+----------------------+----------------------+----------------------+
| \</Interaction\>     |                      |                      |
+----------------------+----------------------+----------------------+

### From Molecule Data to Proposed Model 

  **Data**                                                                                                  **Model**                           **Notes**
  --------------------------------------------------------------------------------------------------------- ----------------------------------- --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
  \<Molecule molecule\_type=\"protein\" id=\"200158\"\>                                                     Not Modeled                         **PathwayInteractionComponent** is one of multiple Molecule-types. A Molecule can be a protein, complex, compound, rna or "molecule-type", the last possibly being (junk data)
  \<Name name\_type=\"PF\" long\_name\_type=\"preferred symbol\" value=\"FRS2 family-active\"/\>            Not Modeled                         
  \<FamilyMemberList\>                                                                                                                          
  \<Member member\_molecule\_idref=\"201289\"\>                                                                                                 
  \<Label label\_type=\"activity-state\" value=\"active\"/\>                                                                                    
  \<PTMExpression\>                                                                                         **PostTranslationalModification**   
  \<PTMTerm protein=\"Q8WU20\" position=\"2\" aa=\"G\" modification=\"myristoylation\"/\>                                                       
  \<PTMTerm protein=\"Q8WU20\" position=\"196\" aa=\"Y\" modification=\"phosphorylation\"/\>                                                    
  \<PTMTerm protein=\"Q8WU20\" position=\"306\" aa=\"Y\" modification=\"phosphorylation\"/\>                                                    
  \<PTMTerm protein=\"Q8WU20\" position=\"349\" aa=\"Y\" modification=\"phosphorylation\"/\>                                                    
  \<PTMTerm protein=\"Q8WU20\" position=\"392\" aa=\"Y\" modification=\"phosphorylation\"/\>                                                    
  \<PTMTerm protein=\"Q8WU20\" position=\"436\" aa=\"Y\" modification=\"phosphorylation\"/\>                                                    
  \</PTMExpression\>                                                                                                                            
  \</Member\>                                                                                                                                   
  \<Member member\_molecule\_idref=\"201290\"\>                                                                                                 
  \<Label label\_type=\"activity-state\" value=\"active\"/\>                                                                                    
  \<PTMExpression\>                                                                                                                             
  \<PTMTerm protein=\"O43559\" position=\"2\" aa=\"G\" modification=\"myristoylation\"/\>                                                       
  \<PTMTerm protein=\"O43559\" position=\"417\" aa=\"Y\" modification=\"phosphorylation\"/\>                                                    
  \<PTMTerm protein=\"O43559\" position=\"455\" aa=\"Y\" modification=\"phosphorylation\"/\>                                                    
  \</PTMExpression\>                                                                                                                            
  \</Member\>                                                                                                                                   
  \</FamilyMemberList\>                                                                                                                         
  \<ComplexComponentList\>                                                                                                                      
  \<ComplexComponent molecule\_idref=\"200523\"\>                                                           Not Modeled                         
  \</ComplexComponent\>                                                                                                                         
  \<ComplexComponent molecule\_idref=\"201460\"\>                                                                                               
  \</ComplexComponent\>                                                                                                                         
  \</ComplexComponentList\>                                                                                                                     
  \<Part whole\_molecule\_idref=\"200268\" part\_molecule\_idref=\"201327\" start=\"217\" end=\"1013\"/\>   Not Modeled                         
  \</Molecule\>                                                                                                                                 

Data Exemplars
==============

### Pathway Data 

\<Pathway id=\"500317\" subnet=\"true\"\>

\<Organism\>Hs\</Organism\>

\<LongName\>Signalling to RAS\</LongName\>

\<ShortName\>Signalling\_to\_RAS\</ShortName\>

\<Source id=\"7\"\>Reactome\</Source\>

\<CuratorList\>

\<Curator\>Nasi, S, Annibali, D\</Curator\>

\<Curator\>Jassal, B\</Curator\>

\</CuratorList\>

\<ReviewerList\>

\<Reviewer\>Greene, LA\</Reviewer\>

\</ReviewerList\>

\<PathwayComponentList\>

\<PathwayComponent interaction\_idref=\"500704\"/\>

\<PathwayComponent interaction\_idref=\"501216\"/\>

\<PathwayComponent interaction\_idref=\"503170\"/\>

\<PathwayComponent interaction\_idref=\"500703\"/\>

\<PathwayComponent interaction\_idref=\"501218\"/\>

\<PathwayComponent interaction\_idref=\"501217\"/\>

\<PathwayComponent interaction\_idref=\"503168\"/\>

\<PathwayComponent interaction\_idref=\"503522\"/\>

\</PathwayComponentList\>

\</Pathway\>

### Interaction Data

\<Interaction interaction\_type=\"modification\" id=\"501031\"\>

\<Source id=\"7\"\>Reactome\</Source\>

\<EvidenceList\>

\<Evidence value=\"NIL\"\>NIL\</Evidence\>

\</EvidenceList\>

\<ReferenceList\>

\<Reference pmid=\"14657031\"\>14657031\</Reference\>

\<Reference pmid=\"11859075\"\>11859075\</Reference\>

\</ReferenceList\>

\<InteractionComponentList\>

\<InteractionComponent role\_type=\"agent\" molecule\_idref=\"502748\"\>

\<Label label\_type=\"location\" value=\"nucleus\"/\>

\</InteractionComponent\>

\<InteractionComponent role\_type=\"input\" molecule\_idref=\"501810\"\>

\<Label label\_type=\"location\" value=\"nucleus\"/\>

\</InteractionComponent\>

\<InteractionComponent role\_type=\"output\"
molecule\_idref=\"501810\"\>

\<Label label\_type=\"location\" value=\"nucleus\"/\>

\</InteractionComponent\>

\</InteractionComponentList\>

\</Interaction\>

### Molecules Data

###   {#section-1 .list-paragraph}

\<Molecule molecule\_type=\"compound\" id=\"503535\"\>

\<Name name\_type=\"CH\" long\_name\_type=\"Chemical Entities of
Biological Int

erest\" value=\"15554\"/\>

\<Name name\_type=\"AS\" long\_name\_type=\"alias\"
value=\"Prostaglandin H2\"/\>

\<Name name\_type=\"AS\" long\_name\_type=\"alias\"
value=\"(5Z,13E)-(15S)-9alpha

,11alpha-Epidioxy-15-hydroxyprosta-5,13-dienoate\"/\>

\<Name name\_type=\"PF\" long\_name\_type=\"preferred symbol\"
value=\"Prostaglan

din H2\"/\>

\</Molecule\>

####  {#section-2 .list-paragraph}

####   {#section-3 .list-paragraph}

  -----------------
  END OF DOCUMENT
  -----------------