# Methods

This is a detailed guide about how interactions are inferred in Reactome.

### Complexes

Every component in a complex is likely to physically interact with each other. However, this probability decreases as the number of components increases. A limit in the number of components can be applied in order to not export these interactions.

``````+ Complex1
|   - EWAS1
|   - EWAS2
|   - SimpleEntity1
``````
Context Interactor A Interactor B Type
Complex1 EWAS1 EWAS2 Physical
Complex1 EWAS1 SimpleEntity1 Physical
Complex1 EWAS2 SimpleEntity1 Physical

Interactions between simple molecules are not exported.

``````+ Complex1
|   - EWAS1
|   - SimpleEntity1
|   - SimpleEntity2
``````
Context Interactor A Interactor B Type
Complex1 EWAS1 SimpleEntity1 Physical
Complex1 EWAS1 SimpleEntity2 Physical

If an element in the complex is present more than one time (stoichiometry > 1) then an interaction with itself is added. We call this molecules olygomers.

``````+ Complex1
|   - 2 x EWAS1
|   - SimpleEntity1
``````
Context Interactor A Interactor B Type
Complex1 0 x EWAS1 2 x EWAS1 Physical
Complex1 2 x EWAS1 SimpleEntity1 Physical

Components of a complex can be other complexes. In that case, each subcomplex is expanded in its components.

``````+ Complex1
|   + Complex2
|   |   - EWAS1
|   |   - EWAS2
|   - SimpleEntity1
``````
Context Interactor A Interactor B Type
Complex2 EWAS1 EWAS2 Physical
Complex1 EWAS1 SimpleEntity1 Physical
Complex1 EWAS2 SimpleEntity1 Physical

Notice that the context for the interaction between EWAS1 and EWAS2 is the subcomplex Complex2. We always use the most specific context for an interaction.

The same rule is applied to Polymers:

``````+ Complex1
|   + Polymer1
|   |   - EWAS1
|   - SimpleEntity1
``````
Context Interactor A Interactor B Type
Complex1 EWAS1 SimpleEntity1 Physical

Members of entity sets do not interact with each other, as elements in entity sets are interchangeable. Candidates are not taken into account.

``````+ Complex1
|   + EntitySet1
|   |   o EWAS1
|   |   o EWAS2
|   - SimpleEntity1
``````
Context Interactor A Interactor B Type
Complex1 EWAS1 SimpleEntity1 Physical
Complex1 EWAS2 SimpleEntity1 Physical

The same interaction can happen in different contexts when they are not subcomponents of each other.

``````+ Complex1
|   - EWAS1
|   - EWAS2
+ Complex2
|   - EWAS1
|   - EWAS2
``````
Context Interactor A Interactor B Type
Complex1 EWAS1 SimpleEntity1 Physical
Complex1 EWAS2 SimpleEntity1 Physical
Complex2 EWAS1 SimpleEntity1 Physical
Complex2 EWAS2 SimpleEntity1 Physical

### Polymers

One interaction is inferred from each polymer: the repeated unit interacts with itself. The stoichiometry for both interactors is 0.

``````+ Polymer1
|   - EWAS1
``````
Context Interactor A Interactor B Type
Polymer1 0 x EWAS1 0 x EWAS1 Physical

Of course, if the repeated unit of a polymer is a complex or an entity set, it must be divided.

``````+ Polymer1
|   - Complex1
|   |   - EWAS1
|   |   - SimpleEntity1
+ Polymer2
|   - EntitySet1
|   |   o EWAS2
|   |   o SimpleEntity2
``````
Context Interactor A Interactor B Type
Polymer1 0 x EWAS1 0 x EWAS1 Physical
Polymer1 0 x EWAS1 0 x SimpleEntity1 Physical
Complex1 1 x EWAS1 1 x SimpleEntity1 Physical
Polymer2 0 x EWAS2 0 x EWAS2 Physical
Polymer2 0 x EWAS2 0 x SimpleEntity2 Physical

### Reactions

Two types of interactions can be inferred from every reaction:

1. The input elements physically interact with each other.
2. The catalyst chemically interacts with every input.

Input interactions are similar to complexes:

``````+ Reaction1
|   i PhysicalEntity1
|   i 4 x PhysicalEntity2
|   i PhysicalEntity3
``````
Context Interactor A Interactor B Type
Reaction1 PhysicalEntity1 4 x PhysicalEntity2 Physical
Reaction1 PhysicalEntity1 PhysicalEntity3 Physical
Reaction1 4 x PhysicalEntity2 PhysicalEntity3 Physical
Reaction1 0 x PhysicalEntity2 4 x PhysicalEntity2 Physical

Catalyst's interactions are chemical.

``````+ Reaction1
|   i PhysicalEntity1
|   c PhysicalEntity2
``````
Context Interactor A Interactor B Type
Reaction1 PhysicalEntity1 PhysicalEntity2 Chemical

The molecule that acts as the catalyst is the active unit of the catalyst activity, if, and only if, one active unit is specified. If zero or more than one active units are specified, then the physical entity is used as catalyst. When the input is the same molecule as the catalyst, no interactions are exported.

The input must be formed by one relevant molecule (protein, complex, polymer) and zero or more small molecules (cofactors). If the input is a set (with or without cofactors), every member of the input is interacted with the catalyst. If the input is just one small molecule, then it is used as input.

The type of this interaction depends on the GO-Molecular-function term associated with the CatalystActivity.

BlackBoxEvents are ignored.

##### Clone this wiki locally
You can’t perform that action at this time.
Press h to open a hovercard with more details.