Major contributions and future works

Recently, there are rapidly increasing number of reliable PPIs which are recorded in many databases, such as IntAct, DIP, MIPS, MINT, and BioGRID. We identified the PPI family which consists of a group of homologous PPIs to provide a description of the functional and evolutionary relationships of PPIs. The new PPI family, which combines the PPI families and SB-PPI families, may be more and more complete and reliable while more reliable PPIs and 3D-structure are identified. Additionally, The PPI family could help biologists to study the comparison of biochemical networks across multiple species. The cross-species network comparison can be used to identify the corresponding pathways from one organism to another.

For systems biology, the comparison of networks provides clues for understanding some important issue, such as evolution of networks.

Some important issues will be discussed in the future. The PPI family could combine with the SB-PPI family for verifying the reliability of the members in a family in older to building the reliable PPI family. Moreover, we also want to know whether this reliable PPI family may have hierarchical relationship as the protein family (e.g., SCOP). Figure 16 shows the hypothesis of the hierarchical relationship in PPI families. A PPI superfamily may consist of more than one PPI family and some PPI families further include many core families. This relationship implies that the evolution may be involved in a protein interacting with another protein. Our major assumption, which considered that a group of homologous PPIs may be from a common ancestry, could be further proved when co-evolution occurs in homologous PPIs of the reliable PPI family.

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Figure 16. The hypothesis of the hierarchical relationship between PPI families.

SuperFamily

Family 1 

Core family  1

Core family  2

Family 2

Core family  1

Family n

…

Figure 16. The hypothesis of the hierarchical relationship between PPI families.

Based on the methods of PPI family and SB-PPI family, we also could verify the PPI in a family, especially these PPIs from large-scale experiments. Each PPI of a family may be scored through a new scoring function in the future. This scoring function may be composed of several scores. For example, the reliability score may consider the existence of crystal structure and the PPI identified by small-scale experiments or many different large-scale experiments. The interface (or interacting domain pair) is highly conserved and important for protein-protein interacting, and the similarity of interface could provide a clue to evaluate a PPI. In addition, the conserved biological properties, such as GO terms, also could be considered biological meaning score according to their highly conservation in our studies. It is useful to construct the reliable PPI family and offer biologists to realize evolutions of homologous PPIs and PPI families.

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Appendix A

List of publications

Journal papers

1. Chen, C.-C., Lin, C.-Y., Lo, Y.-S. and Yang, J.-M. PPISearch: a web server for searching homologous protein-protein interactions across multiple species. Nucleic Acids Research 37:W376-W383 (2009). (Impact factor: 6.878)

2. Lo, Y.-S., Lin, C.-Y. and Yang, J.-M. (2010) PCFamily: a web server for searching homologous protein complexes. Nucleic Acids Research (Accepted)