APID database: redefining protein-protein interaction experimental evidences and binary interactomes

Abstract

The collection and integration of all the known protein-protein physical interactions within a proteome framework are critical to allow proper exploration of the protein interaction networks that drive biological processes in cells at molecular level. APID Interactomes is a public resource of biological data (http://apid.dep.usal.es) that provides a comprehensive and curated collection of `protein interactomes' for more than 1100 organisms, including 30 species with more than 500 interactions, derived from the integration of experimentally detected protein-to-protein physical interactions (PPIs). We have performed an update of APID database including a redefinition of several key properties of the PPIs to provide a more precise data integration and to avoid false duplicated records. This includes the unification of all the PPIs from five primary databases of molecular interactions (BioGRID, DIP, HPRD, IntAct and MINT), plus the information from two original systematic sources of human data and from experimentally resolved 3D structures (i.e. PDBs, Protein Data Bank files, where more than two distinct proteins have been identified). Thus, APID provides PPIs reported in published research articles (with traceable PMIDs) and detected by valid experimental interaction methods that give evidences about such protein interactions (following the `ontology and controlled vocabulary': www.ebi.ac.uk/ols/ontologies/mi; developed by `HUPO PSI-MI'). Within this data mining framework, all interaction detection methods have been grouped into two main types: (i) `binary' physical direct detection methods and (ii) `indirect' methods. As a result of these redefinitions, APID provides unified protein interactomes including the specific `experimental evidences' that support each PPI, indicating whether the interactions can be considered `binary' (i.e. supported by at least one binary detection method) or not.

Figure 1

Presention of the new version of APID (Agile Protein Interactomes DataServer) that includes binary interactomes based in experimental evidences. (A) Panel with a view of the entry page of APID website that shows the human interactomes provided in three quality levels. (B) Table showing the numbers included in APID database about sizes of the binary interactomes, the corresponding reference proteomes and the coverage of the interactome on the proteome (in %) for seven model organisms and for humans.

Figure 2

Comparison of the assignment of experimental interaction detection methods (PSI-MI:ID) done by 2 databases (IntAct and BioGRID), which included a common set of 6689 curated articles (PMID) and 164 682 PPIs. The detection methods are transformed in a network using the links between terms provided by PSI-MI. The networks include all the PSI-MI terms linked to `interaction detection method’ (271 terms, Table 1). Every term is depicted as a node in the network, and if the term is inside a green circle, it indicates that these terms are used to annotate the PPIs found by the corresponding database. (A) Corresponds to the network derived from IntAct data and (B) corresponds to the network derived from BioGRID data. The green circles are proportional to the number of times a term is used, and such circles are placed only when a term of the ontology is used.

Figure 3

(A) Workflow for the PPI records that illustrates the procedure followed in the reconstruction of APID: from the original raw `curation events’ to the final unified `experimental evidences’. (B) View of the new data tables that APID database includes. The example corresponds to the interaction between two proteins (RASH and RGL2) and reveals that despite the existence of six original curation events, this interaction is only supported by four distinct experimental evidences.