2005 Scientific Session Abstracts
Computational Prediction of Protein-Protein Interactions involved Cancer using Peptide Complementarity and apriori Knowledge
Anguraj Sadanandam , (asadanandam@unmc.edu), Michelle L. Varney and Rakesh K. Singh University of Nebraska Medical Center, Omaha, NE
Context: Protein-protein interactions play a major role in the metastasis of cancer cells to distant organs, and the importance of understanding this process has prompted the development of a pipeline for predicting the binding partners of proteins using different theories. Previously, we identified cell adhesion molecules (CAMs) involved in metastatis, utilizing a signature peptide screened using high-throughput techniques. We selected three proteins among the identified CAMs - Semaphorin 5A (Sema5A), Plexin B3 and Neuropilin-2 (NRP-2), and proposed that they may interact with each other.
Technology : The patterns of protein functions were mined from Pubmed and Google Scholar (apriori knowledge) using association rule. In addition to evaluate their interactions, we applied Dwyer and Root-Bernstein/Dillon (RBD) theories of protein evolution that each protein will contain their ligand-like sequences within the binding region. Furthermore, the conserved domain database (CDD) from NCBI was used to check if they share the same functional domains. In addition, the evolutionary phenomenon that the binding partners co-express in same tissues was assessed using virtual northern, SageMap, virtual microarray expression data, dbEST and finally, RT-PCR using respective primers. Above all the hypothesis that these proteins that function together in a pathway or structural complex may have evolved in a correlated fashion was tested using orthologous genes from 18 species. Again, a phylogenetic tree was constructed to evaluate the evolution of all the three proteins.
Results : The evaluation confirmed the presence of homologous copy of the complementary peptide in those proteins. Furthermore, corresponding to the fact that the conserved domains in proteins with common ancestry may physically interact with each other, we found Sema5A and Plexin B3 sharing the same semaphorin domain, through which the other members of their families interacted. In addition, a virtual expression database search and RT-PCR analysis showed correlated mRNA expression for these proteins in spinal cord, prostate cancer and pancreatic cancer. Also, three proteins were found to have evolved together.
Conclusion : These results suggest that Sema5A may interact with Plexin B3 and NRP-2, and same analysis, validated the interaction of Semaphorin 3C with NRP-2 (already reported). Hence, we propose that this sequence of prediction can be used for discovering many unknown interacting partners involved in tumor progression.