Protein Interactomics by Two-Hybrid Methods

  • Soon Gang Choi
  • Aaron Richardson
  • Luke Lambourne
  • David E. Hill
  • Marc VidalEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1794)


Comprehensive identification of direct, physical interactions between biological macromolecules, such as protein–protein, protein–DNA, and protein–RNA interactions, is critical for our understanding of the function of gene products as well as the global organization and interworkings of various molecular machines within the cell. The accurate and comprehensive detection of direct interactions, however, remains a huge challenge due to the inherent structural complexity arising from various post-transcriptional and translational modifications coupled with huge heterogeneity in concentration, affinity, and subcellular location differences existing for any interacting molecules. This has created a need for developing multiple orthogonal and complementary assays for detecting various types of biological interactions. In this introduction, we discuss the methods developed for measuring different types of molecular interactions with an emphasis on direct protein–protein interactions, critical issues for generating high-quality interactome datasets, and the insights into biological networks and human diseases that current interaction mapping efforts provide. Further, we will discuss what future might lie ahead for the continued evolution of two-hybrid methods and the role of interactomics for expanding the advancement of biomedical science.

Key words

Interactome network Interactomics Systems biology Edgetics Protein-protein interaction Two-hybrid 



We thank Yang Wang, Hong Yue, Julien Olivet, and Michael Calderwood for critical reading of the manuscript and their valuable comments. This work was supported by a Claudia Adams Barr Program for Innovative Cancer Research Award to S.G.C., and NHGRI grants U41HG001715, awarded to D.E.H. and M.V., and P50HG004233, awarded to M.V. Soon Gang Choi and Aaron Richardson contributed equally to this work.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Soon Gang Choi
    • 1
    • 2
    • 3
  • Aaron Richardson
    • 1
    • 2
    • 3
  • Luke Lambourne
    • 1
    • 2
    • 3
  • David E. Hill
    • 1
    • 2
    • 3
  • Marc Vidal
    • 1
    • 3
    Email author
  1. 1.Center for Cancer Systems Biology (CCSB)Dana-Farber Cancer InstituteBostonUSA
  2. 2.Department of Cancer BiologyDana-Farber Cancer InstituteBostonUSA
  3. 3.Department of GeneticsHarvard Medical SchoolBostonUSA

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