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About the Authors:
Carson M. Andorf
Current address: United States Department of Agriculture-Agriculture Research Service Corn Insects and Crop Genetics Research Unit, Ames, Iowa, United States of America
Affiliation: Department of Computer Science, Iowa State University, Ames, Iowa, United States of America
Vasant Honavar
Affiliations Department of Computer Science, Iowa State University, Ames, Iowa, United States of America, Bioinformatics and Computational Biology Program, Iowa State University, Ames, Iowa, United States of America
Taner Z. Sen
* E-mail: [email protected]
Affiliations Bioinformatics and Computational Biology Program, Iowa State University, Ames, Iowa, United States of America, United States Department of Agriculture-Agriculture Research Service Corn Insects and Crop Genetics Research Unit, Ames, Iowa, United States of America, Department of Genetics, Development and Cell Biology, Iowa State University, Ames, Iowa, United States of America
Introduction
Proteins are the principal catalytic agents, structural elements, signal transmitters, transporters and molecular machines in cells. Functional annotation of proteins remains one of the most challenging problems in functional genomics, however, our evolving understanding of a proteins' interaction partners helps in functional annotation of proteins [1]. Protein-protein interactions are therefore critical to elucidating the role played by individual proteins in important biological pathways. Such networks are typically constructed using high throughput techniques (e.g., yeast two-hybrid (Y2H) experiments).
Our current understanding of protein-protein interaction networks is quite limited for a variety of reasons. The challenge of reliable and complete determination of the interactome is far from being fully addressed due to the high rate of false positives. These false positives are associated with high throughput experiments, the low coverage of solved co-crystal structures in the Protein Data Bank (PDB), and the difficulty of obtaining reliable negative evidence that a protein does not interact with one or more other proteins. For example, Y2H experiments focus on pair-wise interactions between proteins and provide, at best, rather indirect evidence for higher order interactions e.g., those that require three proteins to come together to form a complex. Even in the case of pairwise interactions, Y2H experiments only provide evidence that a pair of proteins is likely to interact in vitro, without offering any insights into the physical basis of such interactions, or whether such interactions may actually occur in vivo [2]–[6]. It is well known that data from high-throughput Y2H...