IDDI: integrated domain-domain interaction and protein interaction analysis system

Abstract

Background: Deciphering protein-protein interaction (PPI) in domain level enriches valuable information about binding mechanism and functional role of interacting proteins. The 3D structures of complex proteins are reliable source of domain-domain interaction (DDI) but the number of proven structures is very limited. Several resources for the computationally predicted DDI have been generated but they are scattered in various places and their prediction show erratic performances. A well-organized PPI and DDI analysis system integrating these data with fair scoring system is necessary.

Method: We integrated three structure-based DDI datasets and twenty computationally predicted DDI datasets and constructed an interaction analysis system, named IDDI, which enables to browse protein and domain interactions with their relationships. To integrate heterogeneous DDI information, a novel scoring scheme is introduced to determine the reliability of DDI by considering the prediction scores of each DDI and the confidence levels of each prediction method in the datasets, and independencies between predicted datasets. In addition, we connected this DDI information to the comprehensive PPI information and developed a unified interface for the interaction analysis exploring interaction networks at both protein and domain level.

Result: IDDI provides 204,705 DDIs among total 7,351 Pfam domains in the current version. The result presents that total number of DDIs is increased eight times more than that of previous studies. Due to the increment of data, 50.4% of PPIs could be correlated with DDIs which is more than twice of previous resources. Newly designed scoring scheme outperformed the previous system in its accuracy too. User interface of IDDI system provides interactive investigation of proteins and domains in interactions with interconnected way. A specific example is presented to show the efficiency of the systems to acquire the comprehensive information of target protein with PPI and DDI relationships. IDDI is freely available at http://pcode.kaist.ac.kr/iddi/.

Figure 1

Data similarity between each predicted dataset pair based on weighted overlap scores.

Figure 2

Schematic illustration of resource collection, database construction and representation of IDDI.

Figure 3

Data statistics in different DDI databases.

Figure 4

Performance comparisons of reliability scoring schemes between IDDI and UniDomInt (a) with their own DDI datasets and (b) with the same DDI dataset of IDDI.

Figure 5

Example for IDDI functionalities (a) Protein interaction partners of P53 (P04637) having DDI relationship with the P53 transactivation domain (PF08563) (b) Complex information containing P53 and MDM2 (Q00987) (c) Domain interaction partners of P53 transactivation domain (d) DDI information between P53 and Necdin (Q99608).