Reconstructing the topology of protein complexes


Journal Article

Recent advances in high-throughput experimental techniques have enabled the production of a wealth of protein interaction data, rich in both quantity and variety. While the sheer quantity and variety of data present special difficulties for modeling, they also present unique opportunities for gaining insight into protein behavior by leveraging multiple perspectives. Recent work on the modularity of protein interactions has revealed that reasoning about protein interactions at the level of domain interactions can be quite useful. We present PROCTOR, a learning algorithm for reconstructing the internal topology of protein complexes by reasoning at the domain level about both direct protein interaction data (Y2H) and protein co-complex data (AP-MS). While other methods have attempted to use data from both these kinds of assays, they usually require that co-complex data be transformed into pairwise interaction data under a spoke or clique model, a transformation we do not require. We apply PROCTOR to data from eight highthroughput datasets, encompassing 5,925 proteins, essentially all of the yeast proteome. First we show that PROCTOR outperforms other algorithms for predicting domain-domain and protein-protein interactions from Y2H and AP-MS data. Then we show that our algorithm can reconstruct the internal topology of AP-MS purifications, revealing known complexes like Arp2/3 and RNA polymerase II, as well as suggesting new complexes along with their corresponding topologies. © Springer-Verlag Berlin Heidelberg 2007.

Duke Authors

Cited Authors

  • Bernard, A; Vaughn, DS; Hartemink, AJ

Published Date

  • August 3, 2007

Published In

Volume / Issue

  • 4453 LNBI /

Start / End Page

  • 32 - 46

Electronic International Standard Serial Number (EISSN)

  • 1611-3349

International Standard Serial Number (ISSN)

  • 0302-9743

Citation Source

  • Scopus