Interactions are generated electronically based on the data that we store on complexes and reactions, i.e. the interactions provided by Reactome are not curated and are not experimental data. In addition, the complexes and reactions in species other than human are derived by orthology inference from the correspondinghuman complexes and reactions.

The meaning of "interaction" is quite broad: 2 protein sequences occur in the same complex or they occur in the same reaction.

The 1st line begins with '#' and gives the number of unique interactions, i.e. unique pairs if UniProt accession numbers.

The rest of the file is tab delimited with columns having following meaning/content:

Interaction types

In Reactome, complexes can be arbitrarily nested, i.e., contain subcomplexes. Here we have complex C1 consisting of complexes C2 and C3. C2 consist of molecules A and B. C3 consists of molecules C and D:

           C1 --- C2 --- A
                |      |
                |      |- B
                |- C3 --- C
                |- D

Now really to the interaction types:

The 'direct_complex' type doesn't really mean true pairwise interaction. For example, Reactome's representation of ribosomal S60 subunit consists "directly" of 40+ proteins and has no sub-complexes. Obviously this can hardly mean that each one of those component proteins directly interacts with every other protein. Hence, the 'direct_complex' vs. 'indirect_complex' distinction is quite meaningless.

Other notes: