Maximizing binary interactome mapping with a minimal number of assays

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Item Type:

Article

Title:

Maximizing binary interactome mapping with a minimal number of assays

Creators Name:

Choi, S.G. and Olivet, J. and Cassonnet, P. and Vidalain, P.O. and Luck, K. and Lambourne, L. and Spirohn, K. and Lemmens, I. and Dos Santos, M. and Demeret, C. and Jones, L. and Rangarajan, S. and Bian, W. and Coutant, E.P. and Janin, Y.L. and van der Werf, S. and Trepte, P. and Wanker, E.E. and De Las Rivas, J. and Tavernier, J. and Twizere, J.C. and Hao, T. and Hill, D.E. and Vidal, M. and Calderwood, M.A. and Jacob, Y.

Abstract:

Complementary assays are required to comprehensively map complex biological entities such as genomes, proteomes and interactome networks. However, how various assays can be optimally combined to approach completeness while maintaining high precision often remains unclear. Here, we propose a framework for binary protein-protein interaction (PPI) mapping based on optimally combining assays and/or assay versions to maximize detection of true positive interactions, while avoiding detection of random protein pairs. We have engineered a novel NanoLuc two-hybrid (N2H) system that integrates 12 different versions, differing by protein expression systems and tagging configurations. The resulting union of N2H versions recovers as many PPIs as 10 distinct assays combined. Thus, to further improve PPI mapping, developing alternative versions of existing assays might be as productive as designing completely new assays. Our findings should be applicable to systematic mapping of other biological landscapes.

Keywords:

Biological Assay, HEK293 Cells, HeLa Cells, High-Throughput Screening Assays, Protein Databases, Protein Interaction Mapping, Protein Interaction Maps, Proteins, Proteome, Proteomics, Two-Hybrid System Techniques

Source:

Nature Communications

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Volume:

Number:

Page Range:

3907

Date:

29 August 2019