Abstract
Protein–protein interactions are key to many aspects of the cell, including its cytoskeletal structure, the signaling processes in which it is involved, or its metabolism. Failure to form protein complexes or signaling cascades may sometimes translate into pathologic conditions such as cancer or neurodegenerative diseases. The set of all protein interactions between the proteins encoded by an organism constitutes its protein interaction network, representing a scaffold for biological function. Knowing the protein interaction network of an organism, combined with other sources of biological information, can unravel fundamental biological circuits and may help better understand the molecular basics of human diseases. The protein interaction network of an organism can be mapped by combining data obtained from both low-throughput screens, i.e., “one gene at a time” experiments and high-throughput screens, i.e., screens designed to interrogate large sets of proteins at once. In either case, quality controls are required to deal with the inherent imperfect nature of experimental assays. In this chapter, we discuss experimental and statistical methodologies to quantify error rates in high-throughput protein–protein interactions screens.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Alberts B, Johnson A, Lewis J, Raff M, Roberts K, et al. (2002) Molecular Biology of the Cell New York: Garland Science.
Rigaut G, Shevchenko A, Rutz B, Wilm M, Mann M, et al. (1999) A generic protein purification method for protein complex characterization and proteome exploration. Nat Biotechnol 17: 1030–1032.
Bauer A, Kuster B (2003) Affinity purification-mass spectrometry. Powerful tools for the characterization of protein complexes. Eur J Biochem 270: 570–578.
Ewing RM, Chu P, Elisma F, Li H, Taylor P, et al. (2007) Large-scale mapping of human protein–protein interactions by mass spectrometry. Mol Syst Biol 3: 89.
Köcher T, Superti-Furga G (2007) Mass spectrometry-based functional proteomics: from molecular machines to protein networks. Nat Methods 4: 807–815.
Shevchenko A, Schaft D, Roguev A, Pijnappel WW, Stewart AF (2002) Deciphering protein complexes and protein interaction networks by tandem affinity purification and mass spectrometry: analytical perspective. Mol Cell Proteomics 1: 204–212.
Vasilescu J, Figeys D (2006) Mapping protein–protein interactions by mass spectrometry. Curr Opin Biotechnol 17: 394–399.
Fields S, Song O (1989) A novel genetic system to detect protein–protein interactions. Nature 340: 245–246.
Gan X, Kitakawa M, Yoshino K, Oshiro N, Yonezawa K, et al. (2002) Tag-mediated isolation of yeast mitochondrial ribosome and mass spectrometric identification of its new components. Eur J Biochem 269: 5203–5214.
Huang L, Baldwin MA, Maltby DA, Medzihradszky KF, Baker PR, et al. (2002) The identification of protein–protein interactions of the nuclear pore complex of Saccharomyces cerevisiae using high throughput matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry. Mol Cell Proteomics 1: 434–450.
Fields S (2005) High-throughput two-hybrid analysis. The promise and the peril. FEBS J 272: 5391–5399.
Fields S, Sternglanz R (1994) The two-hybrid system: an assay for protein–protein interactions. Trends Genet 10: 286–292.
Ito T, Tashiro K, Muta S, Ozawa R, Chiba T, et al. (2000) Toward a protein–protein interaction map of the budding yeast: A comprehensive system to examine two-hybrid interactions in all possible combinations between the yeast proteins. Proc Natl Acad Sci USA 97: 1143–1147.
Giot L, Bader JS, Brouwer C, Chaudhuri A, Kuang B, et al. (2003) A protein interaction map of Drosophila melanogaster. Science 302: 1727–1736.
Li S, Armstrong CM, Bertin N, Ge H, Milstein S, et al. (2004) A map of the interactome network of the metazoan C. elegans. Science 303: 540–543.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, et al. (2005) Towards a proteome-scale map of the human protein–protein interaction network. Nature 437: 1173–1178.
Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, et al. (2005) A human protein–protein interaction network: a resource for annotating the proteome. Cell 122: 957–968.
Cagney G, Uetz P, Fields S (2001) Two-hybrid analysis of the Saccharomyces cerevisiae 26S proteasome. Physiol Genomics 7: 27–34.
Ho Y, Gruhler A, Heilbut A, Bader GD, Moore L, et al. (2002) Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 415: 180–183.
von Mering C, Krause R, Snel B, Cornell M, Oliver SG, et al. (2002) Comparative assessment of large-scale data sets of protein–protein interactions. Nature 417: 399–403.
D’Haeseleer P, Church GM (2004) Estimating and improving protein interaction error rates. Proc IEEE Comput Syst Bioinform Conf: 216–223.
Hart GT, Ramani AK, Marcotte EM (2006) How complete are current yeast and human protein-interaction networks? Genome Biol 7: 120.
Stumpf MP, Thorne T, de Silva E, Stewart R, An HJ, et al. (2008) Estimating the size of the human interactome. Proc Natl Acad Sci USA 105: 6959–6964.
Venkatesan K, Rual JF, Vazquez A, Stelzl U, Lemmens I, et al. (2009) An empirical framework for binary interactome mapping. Nat Methods 6: 83–90.
Bader JS (2003) Greedily building protein networks with confidence. Bioinformatics 19: 1869–1874.
Bader JS, Chaudhuri A, Rothberg JM, Chant J (2004) Gaining confidence in high-throughput protein interaction networks. Nat Biotechnol 22: 78–85.
Han JD, Bertin N, Hao T, Goldberg DS, Berriz GF, et al. (2004) Evidence for dynamically organized modularity in the yeast protein–protein interaction network. Nature 430: 88–93.
Luscombe NM, Babu MM, Yu H, Snyder M, Teichmann SA, et al. (2004) Genomic analysis of regulatory network dynamics reveals large topological changes. Nature 431: 308–312.
Rachlin J, Cohen DD, Cantor C, Kasif S (2006) Biological context networks: a mosaic view of the interactome. Mol Syst Biol 2: 66.
Bossi A, Lehner B (2009) Tissue specificity and the human protein interaction network. Mol Syst Biol 5: 260.
Braun P, Tasan M, Dreze M, Barrios-Rodiles M, Lemmens I, et al. (2009) An experimentally derived confidence score for binary protein–protein interactions. Nat Methods 6: 91–97.
Stagljar I, Korostensky C, Johnsson N, te Heesen S (1998) A genetic system based on split-ubiquitin for the analysis of interactions between membrane proteins in vivo. Proc Natl Acad Sci USA 95: 5187–5192.
Jansen R, Yu H, Greenbaum D, Kluger Y, Krogan NJ, et al. (2003) A Bayesian networks approach for predicting protein–protein interactions from genomic data. Science 302: 449–453.
Ben-Hur A, Noble WS (2006) Choosing negative examples for the prediction of protein–protein interactions. BMC Bioinformatics 7 Suppl 1: S2.
Gomez A, Domedel N, Cedano J, Pinol J, Querol E (2003) Do current sequence analysis algorithms disclose multifunctional (moonlighting) proteins? Bioinformatics 19: 895–896.
Hastie T, Tibshirani R, Friedman J (2001) The elements of statistical learning. New York: Springer.
Yu H, Braun P, Yildirim MA, Lemmens I, Venkatesan K, et al. (2008) High-quality binary protein interaction map of the yeast interactome network. Science 322: 104–110.
Akaike H (1974) A new look at the statistical model identification. IEEE Trans Aut Cont AC-19: 716–723.
Chen M-H, Shao Q-M, Ibrahim JG (2000) Monte Carlo methods in Bayesian computation. New York: Springer. xiii, pp. 386.
Vinayagam A, Stelzl U, Wanker EE (2010) Repeated two-hybrid screening detects transient protein–protein interactions Theoretical Chemistry Accounts 125: 613–619.
Acknowledgments
AV is supported by the RWJ Foundation, Project title: “Strengthening the Cancer Institute of New Jersey in Cancer Prevention, Control and Population Science to Improve Cancer Care,” Cancer Informatics Category. JFR is supported by a fellowship from the Deutsche José Carreras Leukämie-Stiftung e. V. We thank past and current members of the Barabasi, Roth, Tavernier, Vidal, and Wanker Labs for helpful discussions during the development of the empirical framework for binary PIN mapping.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Vazquez, A., Rual, JF., Venkatesan, K. (2011). Quality Control Methodology for High-Throughput Protein–Protein Interaction Screening. In: Cagney, G., Emili, A. (eds) Network Biology. Methods in Molecular Biology, vol 781. Humana Press. https://doi.org/10.1007/978-1-61779-276-2_13
Download citation
DOI: https://doi.org/10.1007/978-1-61779-276-2_13
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-275-5
Online ISBN: 978-1-61779-276-2
eBook Packages: Springer Protocols