Skip to main content
SpringerLink
Log in

Protein-Protein Interaction Databases

  • Protocol
Protein-Protein Interactions

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1278))

Abstract

Years of meticulous curation of scientific literature and increasingly reliable computational predictions have resulted in creation of vast databases of protein interaction data. Over the years, these repositories have become a basic framework in which experiments are analyzed and new directions of research are explored. Here we present an overview of the most widely used protein-protein interaction databases and the methods they employ to gather, combine, and predict interactions. We also point out the trade-off between comprehensiveness and accuracy and the main pitfall scientists have to be aware before adopting protein interaction databases in any single-gene or genome-wide analysis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Croft D, O’Kelly G, Wu G, Haw R et al (2011) Reactome: a database of reactions, pathways and biological processes. Nucleic Acids Res 39:D691–D697

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Kanehisa M, Goto S, Furumichi M, Tanabe M et al (2010) KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res 38:D355–D360

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Kerrien S, Aranda B, Breuza L, Bridge A et al (2012) The IntAct molecular interaction database in 2012. Nucleic Acids Res 40:D841–D846

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Stark C, Breitkreutz B-J, Chatr-Aryamontri A, Boucher L et al (2011) The BioGRID Interaction Database: 2011 update. Nucleic Acids Res 39:D698–D704

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Szklarczyk D, Franceschini A, Kuhn M, Simonovic M et al (2011) The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 39:D561–D568

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Warde-Farley D, Donaldson SL, Comes O, Zuberi K et al (2010) The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res 38:W214–W220

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Goel R, Harsha HC, Pandey A, Prasad TSK (2012) Human Protein Reference Database and Human Proteinpedia as resources for phosphoproteome analysis. Mol Biosyst 8:453–463

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Cherry JM, Hong EL, Amundsen C, Balakrishnan R et al (2012) Saccharomyces Genome Database: the genomics resource of budding yeast. Nucleic Acids Res 40:D700–D705

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Murali T, Pacifico S, Yu J, Guest S et al (2011) DroID 2011: a comprehensive, integrated resource for protein, transcription factor, RNA and gene interactions for Drosophila. Nucleic Acids Res 39:D736–D743

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Goodman N, McCormick K, Goldowitz D, Hockly E et al (2003) Plans for HDBase—a research community website for Huntington’s Disease. Clin Neurosci Res 3:197–217

    Article  Google Scholar 

  11. Lechner M, Höhn V, Brauner B, Dunger I et al (2012) CIDeR: multifactorial interaction networks in human diseases. Genome Biol 13:R62

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Dinkel H, Chica C, Via A, Gould CM et al (2011) Phospho.ELM: a database of phosphorylation sites–update 2011. Nucleic Acids Res 39:D261–D267

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Caspi R, Foerster H, Fulcher CA, Kaipa P et al (2008) The MetaCyc Database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases. Nucleic Acids Res 36:D623–D631

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Smoot ME, Ono K, Ruscheinski J, Wang P-L et al (2011) Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 27:431–432

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Brown KR, Otasek D, Ali M, McGuffin MJ et al (2009) NAViGaTOR: Network Analysis, Visualization and Graphing Toronto. Bioinformatics 25:3327–3329

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Gene T., Consortium O. (2010) The Gene Ontology Consortium in 2010: extensions and refinements. Nucleic Acids Res 38:D331–D335

    Article  Google Scholar 

  17. Hakes L, Robertson DL, Oliver SG (2005) Effect of dataset selection on the topological interpretation of protein interaction networks. BMC Genomics 6:131

    Article  PubMed Central  PubMed  Google Scholar 

  18. Salwinski L, Miller CS, Smith AJ, Pettit FK et al (2004) The Database of Interacting Proteins: 2004 update. Nucleic Acids Res 32:D449–D451

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Salwinski L, Eisenberg D (2007) The MiSink Plugin: cytoscape as a graphical interface to the Database of Interacting Proteins. Bioinformatics 23:2193–2195

    Article  CAS  PubMed  Google Scholar 

  20. Deane CM, Salwiński Ł, Xenarios I, Eisenberg D (2002) Protein interactions: two methods for assessment of the reliability of high throughput observations. Mol Cell Proteomics 1:349–356

    Article  CAS  PubMed  Google Scholar 

  21. Deng M, Mehta S, Sun F, Chen T (2002) Inferring domain-domain interactions from protein-protein interactions. Genome Res 12:1540–1548

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Graeber TG, Eisenberg D (2001) Bioinformatic identification of potential autocrine signaling loops in cancers from gene expression profiles. Nat Genet 29:295–300

    Article  CAS  PubMed  Google Scholar 

  23. Hastings J, de Matos P, Dekker A, Ennis M et al (2013) The ChEBI reference database and ontology for biologically relevant chemistry: enhancements for 2013. Nucleic Acids Res 41:D456–D463

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Ceol A, Chatr Aryamontri A, Licata L, Peluso D et al (2010) MINT, the molecular interaction database: 2009 update. Nucleic Acids Res 38:D532–D539

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Persico M, Ceol A, Gavrila C, Hoffmann R et al (2005) HomoMINT: an inferred human network based on orthology mapping of protein interactions discovered in model organisms. BMC Bioinformatics 6(Suppl 4):S21

    Article  PubMed Central  PubMed  Google Scholar 

  26. Chatr-aryamontri A, Ceol A, Peluso D, Nardozza A et al (2009) VirusMINT: a viral protein interaction database. Nucleic Acids Res 37:D669–D673

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Ceol A, Chatr-aryamontri A, Santonico E, Sacco R et al (2007) DOMINO: a database of domain-peptide interactions. Nucleic Acids Res 35:D557–D560

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Amberger J, Bocchini C, Hamosh A (2011) A new face and new challenges for Online Mendelian Inheritance in Man (OMIM®). Hum Mutat 32:564–567

    Article  PubMed  Google Scholar 

  29. Kandasamy K, Mohan SS, Raju R, Keerthikumar S et al (2010) NetPath: a public resource of curated signal transduction pathways. Genome Biol 11:R3

    Article  PubMed Central  PubMed  Google Scholar 

  30. Breuer K, Foroushani AK, Laird MR, Chen C et al (2013) InnateDB: systems biology of innate immunity and beyond–recent updates and continuing curation. Nucleic Acids Res 41:D1228–D1233

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Bader GD, Donaldson I, Wolting C, Ouellette BF et al (2001) BIND–The Biomolecular Interaction Network Database. Nucleic Acids Res 29:242–245

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Royer L, Reimann M, Andreopoulos B, Schroeder M (2008) Unraveling protein networks with power graph analysis. PLoS Comput Biol 4:e1000108

    Article  PubMed Central  PubMed  Google Scholar 

  33. Barsky A, Gardy JL, Hancock REW, Munzner T (2007) Cerebral: a Cytoscape plugin for layout of and interaction with biological networks using subcellular localization annotation. Bioinformatics 23:1040–1042

    Article  CAS  PubMed  Google Scholar 

  34. Fu W, Sanders-Beer BE, Katz KS, Maglott DR et al (2009) Human immunodeficiency virus type 1, human protein interaction database at NCBI. Nucleic Acids Res 37:D417–D422

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Resource Coordinators NCBI (2013) Database resources of the National Center for Biotechnology Information. Nucleic Acids Res 41:D8–D20

    Article  Google Scholar 

  36. Chen R, Jeong SS (2000) Functional prediction: identification of protein orthologs and paralogs. Protein Sci 9:2344–2353

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Niu Y, Otasek D, Jurisica I (2010) Evaluation of linguistic features useful in extraction of interactions from PubMed; application to annotating known, high-throughput and predicted interactions in I2D. Bioinformatics 26:111–119

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Hermjakob H, Montecchi-Palazzi L, Bader G, Wojcik J et al (2004) The HUPO PSI’s molecular interaction format–a community standard for the representation of protein interaction data. Nat Biotechnol 22:177–183

    Article  CAS  PubMed  Google Scholar 

  39. Hart GT, Ramani AK, Marcotte EM (2006) How complete are current yeast and human protein-interaction networks? Genome Biol 7:120

    Article  PubMed Central  PubMed  Google Scholar 

  40. Burns DM, Horn V, Paluh J, Yanofsky C (1990) Evolution of the tryptophan synthetase of fungi. Analysis of experimentally fused Escherichia coli tryptophan synthetase alpha and beta chains. J Biol Chem 265:2060–2069

    CAS  PubMed  Google Scholar 

  41. Enright AJ, Iliopoulos I, Kyrpides NC, Ouzounis CA (1999) Protein interaction maps for complete genomes based on gene fusion events. Nature 402:86–90

    Article  CAS  PubMed  Google Scholar 

  42. Marcotte EM, Pellegrini M, Ng HL, Rice DW et al (1999) Detecting protein function and protein-protein interactions from genome sequences. Science 285:751–753

    Article  CAS  PubMed  Google Scholar 

  43. Dandekar T, Snel B, Huynen M, Bork P (1998) Conservation of gene order: a fingerprint of proteins that physically interact. Trends Biochem Sci 23:324–328

    Article  CAS  PubMed  Google Scholar 

  44. Overbeek R, Fonstein M, D’Souza M, Pusch GD et al (1999) Use of contiguity on the chromosome to predict functional coupling. In Silico Biol 1:93–108

    CAS  PubMed  Google Scholar 

  45. Eisen MB, Spellman PT, Brown PO, Botstein D (1998) Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A 95:14863–14868

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Barrett T, Troup DB, Wilhite SE, Ledoux P et al (2011) NCBI GEO: archive for functional genomics data sets–10 years on. Nucleic Acids Res 39:D1005–D1010

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Hirschman L, Park JC, Tsujii J, Wong L et al (2002) Accomplishments and challenges in literature data mining for biology. Bioinformatics 18:1553–1561

    Article  CAS  PubMed  Google Scholar 

  48. Kuhn M, Szklarczyk D, Franceschini A, von Mering C et al (2012) STITCH 3: zooming in on protein-chemical interactions. Nucleic Acids Res 40:D876–D880

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Powell S, Szklarczyk D, Trachana K, Roth A et al (2012) eggNOG v3.0: orthologous groups covering 1133 organisms at 41 different taxonomic ranges. Nucleic Acids Res 40:D284–D289

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. McDowall MD, Scott MS, Barton GJ (2009) PIPs: human protein-protein interaction prediction database. Nucleic Acids Res 37:D651–D656

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Chautard E, Fatoux-Ardore M, Ballut L, Thierry-Mieg N et al (2011) MatrixDB, the extracellular matrix interaction database. Nucleic Acids Res 39:D235–D240

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Goll J, Rajagopala SV, Shiau SC, Wu H et al (2008) MPIDB: the microbial protein interaction database. Bioinformatics 24:1743–1744

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Lynn DJ, Winsor GL, Chan C, Richard N et al (2008) InnateDB: facilitating systems-level analyses of the mammalian innate immune response. Mol Syst Biol 4:218

    Article  PubMed Central  PubMed  Google Scholar 

  54. The UniProt Consortium (2011) Ongoing and future developments at the Universal Protein Resource. Nucleic Acids Res 39:D214–D219

    Article  PubMed Central  Google Scholar 

  55. Aranda B, Blankenburg H, Kerrien S, Brinkman FSL et al (2011) PSICQUIC and PSISCORE: accessing and scoring molecular interactions. Nat Methods 8:528–529

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Sambourg L, Thierry-Mieg N (2010) New insights into protein-protein interaction data lead to increased estimates of the S cerevisiae interactome size. BMC Bioinformatics 11:605

    Article  PubMed Central  PubMed  Google Scholar 

  57. Nakayama M, Kikuno R, Ohara O (2002) Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs. Genome Res 12:1773–1784

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Jeong H, Tombor B, Albert R, Oltvai ZN et al (2000) The large-scale organization of metabolic networks. Nature 407:651–654

    Article  CAS  PubMed  Google Scholar 

  59. Wuchty S, Oltvai ZN, Barabási A-L (2003) Evolutionary conservation of motif constituents in the yeast protein interaction network. Nat Genet 35:176–179

    Article  CAS  PubMed  Google Scholar 

  60. Von Mering C, Krause R, Snel B, Cornell M et al (2002) Comparative assessment of large-scale data sets of protein-protein interactions. Nature 417:399–403

    Article  Google Scholar 

  61. Ioannidis JPA (2005) Why most published research findings are false. PLoS Med 2:e124

    Article  PubMed Central  PubMed  Google Scholar 

  62. Tang JL (2005) Selection bias in meta-analyses of gene-disease associations. PLoS Med 2:e409

    Article  PubMed Central  PubMed  Google Scholar 

  63. Pál C, Papp B, Hurst LD (2003) Genomic function: rate of evolution and gene dispensability. Nature 421:496–497, discussion 497–8

    Article  PubMed  Google Scholar 

  64. Bloom JD, Adami C (2003) Apparent dependence of protein evolutionary rate on number of interactions is linked to biases in protein-protein interactions data sets. BMC Evol Biol 3:21

    Article  PubMed Central  PubMed  Google Scholar 

  65. Brito GC, Andrews DW (2011) Removing bias against membrane proteins in interaction networks. BMC Syst Biol 5:169

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Health Sciences, Novo Nordisk Foundation Centre for Protein Research, University of Copenhagen, Blegdamsvej 3B, 2200, København N, Denmark

    Damian Szklarczyk & Lars Juhl Jensen

Authors
  1. Damian Szklarczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lars Juhl Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lars Juhl Jensen .

Editor information

Editors and Affiliations

  1. Department of Pharmacology and Emory Chemical Biology Discovery Center, Emory University School of Medicine, Atlanta, Georgia, USA

    Cheryl L. Meyerkord

  2. Department of Pharmacology, Department of Hematology & Medical Oncology, and Emory Chemical Biology Discovery Center, Emory University School of Medicine, Atlanta, USA

    Haian Fu

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

Szklarczyk, D., Jensen, L.J. (2015). Protein-Protein Interaction Databases. In: Meyerkord, C., Fu, H. (eds) Protein-Protein Interactions. Methods in Molecular Biology, vol 1278. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2425-7_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2425-7_3

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2424-0

  • Online ISBN: 978-1-4939-2425-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation