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PMID: 16762047 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Comprehensive curation and analysis of global interaction networks in Saccharomyces cerevisiae.

Journal of biology ·Vol. 5 ·No. 4 ·2006-00-00 ·Pages 11

Reguly T, Breitkreutz A, Boucher L, Breitkreutz BJ, Hon GC, Myers CL, Parsons A, Friesen H, Oughtred R, Tong A, Stark C, Ho Y, Botstein D, Andrews B, Boone C, Troyanskya OG, Ideker T, Dolinski K, Batada NN, Tyers M

Abstract

The study of complex biological networks and prediction of gene function has been enabled by high-throughput (HTP) methods for detection of genetic and protein interactions. Sparse coverage in HTP datasets may, however, distort network properties and confound predictions. Although a vast number of well substantiated interactions are recorded in the scientific literature, these data have not yet been distilled into networks that enable system-level inference. We describe here a comprehensive database of genetic and protein interactions, and associated experimental evidence, for the budding yeast Saccharomyces cerevisiae, as manually curated from over 31,793 abstracts and online publications. This literature-curated (LC) dataset contains 33,311 interactions, on the order of all extant HTP datasets combined. Surprisingly, HTP protein-interaction datasets currently achieve only around 14% coverage of the interactions in the literature. The LC network nevertheless shares attributes with HTP networks, including scale-free connectivity and correlations between interactions, abundance, localization, and expression. We find that essential genes or proteins are enriched for interactions with other essential genes or proteins, suggesting that the global network may be functionally unified. This interconnectivity is supported by a substantial overlap of protein and genetic interactions in the LC dataset. We show that the LC dataset considerably improves the predictive power of network-analysis approaches. The full LC dataset is available at the BioGRID (http://www.thebiogrid.org) and SGD (http://www.yeastgenome.org/) databases. Comprehensive datasets of biological interactions derived from the primary literature provide critical benchmarks for HTP methods, augment functional prediction, and reveal system-level attributes of biological networks.

MeSH Terms
Computational Biology Protein Interaction Mapping Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism
Chemicals
Saccharomyces cerevisiae Proteins
Authors & Affiliations
20 authors, click to expand affiliations / ORCID
Reguly Teresa
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto ON M5G 1X5, Canada.
Breitkreutz Ashton
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto ON M5G 1X5, Canada.
Boucher Lorrie
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto ON M5G 1X5, Canada. | Department of Medical Genetics and Microbiology, University of Toronto, Toronto ON M5S 1A8, Canada.
Breitkreutz Bobby-Joe
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto ON M5G 1X5, Canada.
Hon Gary C
Department of Bioengineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA.
Myers Chad L
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Washington Road, Princeton, NJ 08544, USA. | Department of Computer Science, Princeton University, NJ 08544, USA.
Parsons Ainslie
Department of Medical Genetics and Microbiology, University of Toronto, Toronto ON M5S 1A8, Canada. | Banting and Best Department of Medical Research, University of Toronto, Toronto ON M5G 1L6, Canada.
Friesen Helena
Banting and Best Department of Medical Research, University of Toronto, Toronto ON M5G 1L6, Canada.
Oughtred Rose
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Washington Road, Princeton, NJ 08544, USA.
Tong Amy
Department of Medical Genetics and Microbiology, University of Toronto, Toronto ON M5S 1A8, Canada. | Banting and Best Department of Medical Research, University of Toronto, Toronto ON M5G 1L6, Canada.
Stark Chris
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto ON M5G 1X5, Canada.
Ho Yuen
Banting and Best Department of Medical Research, University of Toronto, Toronto ON M5G 1L6, Canada.
Botstein David
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Washington Road, Princeton, NJ 08544, USA.
Andrews Brenda
Department of Medical Genetics and Microbiology, University of Toronto, Toronto ON M5S 1A8, Canada. | Banting and Best Department of Medical Research, University of Toronto, Toronto ON M5G 1L6, Canada.
Boone Charles
Department of Medical Genetics and Microbiology, University of Toronto, Toronto ON M5S 1A8, Canada. | Banting and Best Department of Medical Research, University of Toronto, Toronto ON M5G 1L6, Canada.
Troyanskya Olga G
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Washington Road, Princeton, NJ 08544, USA. | Department of Computer Science, Princeton University, NJ 08544, USA.
Ideker Trey
Department of Bioengineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA.
Dolinski Kara
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Washington Road, Princeton, NJ 08544, USA.
Batada Nizar N
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto ON M5G 1X5, Canada.
Tyers Mike
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto ON M5G 1X5, Canada. | Department of Medical Genetics and Microbiology, University of Toronto, Toronto ON M5S 1A8, Canada.
References (106)
106 references, click to expand
  1. Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization.
    Mol Biol Cell. 1998 Dec;9(12):3273-97 PMID: 9843569
  2. Functional organization of the yeast proteome by systematic analysis of protein complexes.
    Nature. 2002 Jan 10;415(6868):141-7 PMID: 11805826
  3. A robust toolkit for functional profiling of the yeast genome.
    Mol Cell. 2004 Nov 5;16(3):487-96 PMID: 15525520
  4. BIND: the Biomolecular Interaction Network Database.
    Nucleic Acids Res. 2003 Jan 1;31(1):248-50 PMID: 12519993
  5. Some protein interaction data do not exhibit power law statistics.
    FEBS Lett. 2005 Sep 26;579(23):5140-4 PMID: 16143331
  6. KEGG: kyoto encyclopedia of genes and genomes.
    Nucleic Acids Res. 2000 Jan 1;28(1):27-30 PMID: 10592173
  7. Motifs, themes and thematic maps of an integrated Saccharomyces cerevisiae interaction network.
    J Biol. 2005;4(2):6 PMID: 15982408
  8. Cluster analysis and display of genome-wide expression patterns.
    Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8 PMID: 9843981
  9. Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth.
    Nature. 2000 Jul 6;406(6791):90-4 PMID: 10894548
  10. Development of human protein reference database as an initial platform for approaching systems biology in humans.
    Genome Res. 2003 Oct;13(10):2363-71 PMID: 14525934
  11. Emergence of scaling in random networks
    Science. 1999 Oct 15;286(5439):509-12 PMID: 10521342
  12. Modular organization of cellular networks.
    Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1128-33 PMID: 12538875
  13. A map of the interactome network of the metazoan C. elegans.
    Science. 2004 Jan 23;303(5657):540-3 PMID: 14704431
  14. A comprehensive two-hybrid analysis to explore the yeast protein interactome.
    Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4569-74 PMID: 11283351
  15. A probabilistic functional network of yeast genes.
    Science. 2004 Nov 26;306(5701):1555-8 PMID: 15567862
  16. Hierarchical organization of modularity in metabolic networks.
    Science. 2002 Aug 30;297(5586):1551-5 PMID: 12202830
  17. New components of a system for phosphate accumulation and polyphosphate metabolism in Saccharomyces cerevisiae revealed by genomic expression analysis.
    Mol Biol Cell. 2000 Dec;11(12):4309-21 PMID: 11102525
  18. Evidence for dynamically organized modularity in the yeast protein-protein interaction network.
    Nature. 2004 Jul 1;430(6995):88-93 PMID: 15190252
  19. Systematic genetic analysis with ordered arrays of yeast deletion mutants.
    Science. 2001 Dec 14;294(5550):2364-8 PMID: 11743205
  20. Functional discovery via a compendium of expression profiles.
    Cell. 2000 Jul 7;102(1):109-26 PMID: 10929718
  21. A comprehensive evolutionary classification of proteins encoded in complete eukaryotic genomes.
    Genome Biol. 2004;5(2):R7 PMID: 14759257
  22. Increasing specificity in high-throughput yeast two-hybrid experiments.
    Methods. 2004 Apr;32(4):363-70 PMID: 15003598
  23. Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
    Nature. 2006 Mar 30;440(7084):637-43 PMID: 16554755
  24. Combining biological networks to predict genetic interactions.
    Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15682-7 PMID: 15496468
  25. The Gene Ontology (GO) database and informatics resource.
    Nucleic Acids Res. 2004 Jan 1;32(Database issue):D258-61 PMID: 14681407
  26. Textpresso: an ontology-based information retrieval and extraction system for biological literature.
    PLoS Biol. 2004 Nov;2(11):e309 PMID: 15383839
  27. Text-mining and information-retrieval services for molecular biology.
    Genome Biol. 2005;6(7):224 PMID: 15998455
  28. BioGRID: a general repository for interaction datasets.
    Nucleic Acids Res. 2006 Jan 1;34(Database issue):D535-9 PMID: 16381927
  29. Global analysis of protein localization in budding yeast.
    Nature. 2003 Oct 16;425(6959):686-91 PMID: 14562095
  30. Towards a proteome-scale map of the human protein-protein interaction network.
    Nature. 2005 Oct 20;437(7062):1173-8 PMID: 16189514
  31. Global analysis of protein expression in yeast.
    Nature. 2003 Oct 16;425(6959):737-41 PMID: 14562106
  32. MINT: a Molecular INTeraction database.
    FEBS Lett. 2002 Feb 20;513(1):135-40 PMID: 11911893
  33. Cytoscape: a software environment for integrated models of biomolecular interaction networks.
    Genome Res. 2003 Nov;13(11):2498-504 PMID: 14597658
  34. Specificity and stability in topology of protein networks.
    Science. 2002 May 3;296(5569):910-3 PMID: 11988575
  35. Whole-genome expression analysis of snf/swi mutants of Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3364-9 PMID: 10725359
  36. On the number of protein-protein interactions in the yeast proteome.
    Nucleic Acids Res. 2003 Jul 15;31(14):4157-61 PMID: 12853633
  37. The COG database: an updated version includes eukaryotes.
    BMC Bioinformatics. 2003 Sep 11;4:41 PMID: 12969510
  38. Formation of regulatory patterns during signal propagation in a Mammalian cellular network.
    Science. 2005 Aug 12;309(5737):1078-83 PMID: 16099987
  39. The HUPO PSI's molecular interaction format--a community standard for the representation of protein interaction data.
    Nat Biotechnol. 2004 Feb;22(2):177-83 PMID: 14755292
  40. Harvesting the genome's bounty: integrative genomics.
    Cold Spring Harb Symp Quant Biol. 2003;68:431-43 PMID: 15338646
  41. Ontological visualization of protein-protein interactions.
    BMC Bioinformatics. 2005;6:29 PMID: 15707487
  42. FTICR mass spectrometry for qualitative and quantitative bioanalyses.
    Curr Opin Biotechnol. 2004 Feb;15(1):3-11 PMID: 15102459
  43. Conserved patterns of protein interaction in multiple species.
    Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):1974-9 PMID: 15687504
  44. Genomic expression programs in the response of yeast cells to environmental changes.
    Mol Biol Cell. 2000 Dec;11(12):4241-57 PMID: 11102521
  45. A Bayesian framework for combining heterogeneous data sources for gene function prediction (in Saccharomyces cerevisiae).
    Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8348-53 PMID: 12826619
  46. The yeast cell-cycle network is robustly designed.
    Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4781-6 PMID: 15037758
  47. MIPS: a database for genomes and protein sequences.
    Nucleic Acids Res. 2002 Jan 1;30(1):31-4 PMID: 11752246
  48. Is there a bias in proteome research?
    Genome Res. 2001 Dec;11(12):1971-3 PMID: 11731485
  49. Evolutionary rate in the protein interaction network.
    Science. 2002 Apr 26;296(5568):750-2 PMID: 11976460
  50. Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p.
    Mol Biol Cell. 2001 Oct;12(10):2987-3003 PMID: 11598186
  51. Network motifs in the transcriptional regulation network of Escherichia coli.
    Nat Genet. 2002 May;31(1):64-8 PMID: 11967538
  52. Global mapping of the yeast genetic interaction network.
    Science. 2004 Feb 6;303(5659):808-13 PMID: 14764870
  53. A Bayesian networks approach for predicting protein-protein interactions from genomic data.
    Science. 2003 Oct 17;302(5644):449-53 PMID: 14564010
  54. A protein interaction map of Drosophila melanogaster.
    Science. 2003 Dec 5;302(5651):1727-36 PMID: 14605208
  55. Transcriptional regulatory code of a eukaryotic genome.
    Nature. 2004 Sep 2;431(7004):99-104 PMID: 15343339
  56. Life cycles of successful genes.
    Trends Genet. 2003 Feb;19(2):79-81 PMID: 12547515
  57. Global analysis of protein phosphorylation in yeast.
    Nature. 2005 Dec 1;438(7068):679-84 PMID: 16319894
  58. An automated method for finding molecular complexes in large protein interaction networks.
    BMC Bioinformatics. 2003 Jan 13;4:2 PMID: 12525261
  59. Lethality and centrality in protein networks.
    Nature. 2001 May 3;411(6833):41-2 PMID: 11333967
  60. The FlyBase database of the Drosophila genome projects and community literature.
    Nucleic Acids Res. 2003 Jan 1;31(1):172-5 PMID: 12519974
  61. Consolidating the set of known human protein-protein interactions in preparation for large-scale mapping of the human interactome.
    Genome Biol. 2005;6(5):R40 PMID: 15892868
  62. Global architecture of genetic interactions on the protein network.
    Nat Biotechnol. 2003 May;21(5):490-1 PMID: 12721566
  63. Correlation between transcriptome and interactome mapping data from Saccharomyces cerevisiae.
    Nat Genet. 2001 Dec;29(4):482-6 PMID: 11694880
  64. Does selection mold molecular networks?
    Sci STKE. 2003 Sep 30;2003(202):PE41 PMID: 14519859
  65. Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry.
    Nature. 2002 Jan 10;415(6868):180-3 PMID: 11805837
  66. DNA helicase gene interaction network defined using synthetic lethality analyzed by microarray.
    Nat Genet. 2003 Nov;35(3):277-86 PMID: 14566339
  67. The Yeast Protein Database (YPD): a curated proteome database for Saccharomyces cerevisiae.
    Nucleic Acids Res. 1998 Jan 1;26(1):68-72 PMID: 9399803
  68. IntAct: an open source molecular interaction database.
    Nucleic Acids Res. 2004 Jan 1;32(Database issue):D452-5 PMID: 14681455
  69. Functional genomics and proteomics: charting a multidimensional map of the yeast cell.
    Trends Cell Biol. 2003 Jul;13(7):344-56 PMID: 12837605
  70. PreBIND and Textomy--mining the biomedical literature for protein-protein interactions using a support vector machine.
    BMC Bioinformatics. 2003 Mar 27;4:11 PMID: 12689350
  71. Saccharomyces Genome Database (SGD) provides tools to identify and analyze sequences from Saccharomyces cerevisiae and related sequences from other organisms.
    Nucleic Acids Res. 2004 Jan 1;32(Database issue):D311-4 PMID: 14681421
  72. DIP, the Database of Interacting Proteins: a research tool for studying cellular networks of protein interactions.
    Nucleic Acids Res. 2002 Jan 1;30(1):303-5 PMID: 11752321
  73. Proteome survey reveals modularity of the yeast cell machinery.
    Nature. 2006 Mar 30;440(7084):631-6 PMID: 16429126
  74. Protein complexes and functional modules in molecular networks.
    Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12123-8 PMID: 14517352
  75. Functional profiling of the Saccharomyces cerevisiae genome.
    Nature. 2002 Jul 25;418(6896):387-91 PMID: 12140549
  76. A new approach to decoding life: systems biology.
    Annu Rev Genomics Hum Genet. 2001;2:343-72 PMID: 11701654
  77. Inparanoid: a comprehensive database of eukaryotic orthologs.
    Nucleic Acids Res. 2005 Jan 1;33(Database issue):D476-80 PMID: 15608241
  78. The GRID: the General Repository for Interaction Datasets.
    Genome Biol. 2003;4(3):R23 PMID: 12620108
  79. Osprey: a network visualization system.
    Genome Biol. 2003;4(3):R22 PMID: 12620107
  80. Schizosaccharomyces pombe essential genes: a pilot study.
    Genome Res. 2003 Mar;13(3):399-406 PMID: 12618370
  81. Reactome: a knowledgebase of biological pathways.
    Nucleic Acids Res. 2005 Jan 1;33(Database issue):D428-32 PMID: 15608231
  82. No simple dependence between protein evolution rate and the number of protein-protein interactions: only the most prolific interactors tend to evolve slowly.
    BMC Evol Biol. 2003 Jan 6;3:1 PMID: 12515583
  83. Stochastic model of protein-protein interaction: why signaling proteins need to be colocalized.
    Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6445-9 PMID: 15096590
  84. Transcriptional networks: reverse-engineering gene regulation on a global scale.
    Curr Opin Microbiol. 2004 Dec;7(6):638-46 PMID: 15556037
  85. A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae.
    Nature. 2000 Feb 10;403(6770):623-7 PMID: 10688190
  86. Integrated genomic and proteomic analyses of a systematically perturbed metabolic network.
    Science. 2001 May 4;292(5518):929-34 PMID: 11340206
  87. Gaining confidence in high-throughput protein interaction networks.
    Nat Biotechnol. 2004 Jan;22(1):78-85 PMID: 14704708
  88. Transcriptional remodeling in response to iron deprivation in Saccharomyces cerevisiae.
    Mol Biol Cell. 2004 Mar;15(3):1233-43 PMID: 14668481
  89. Exploring the metabolic and genetic control of gene expression on a genomic scale.
    Science. 1997 Oct 24;278(5338):680-6 PMID: 9381177
  90. Sequencing and comparison of yeast species to identify genes and regulatory elements.
    Nature. 2003 May 15;423(6937):241-54 PMID: 12748633
  91. Comparative assessment of large-scale data sets of protein-protein interactions.
    Nature. 2002 May 23;417(6887):399-403 PMID: 12000970
  92. Analyzing yeast protein-protein interaction data obtained from different sources.
    Nat Biotechnol. 2002 Oct;20(10):991-7 PMID: 12355115
  93. A human protein-protein interaction network: a resource for annotating the proteome.
    Cell. 2005 Sep 23;122(6):957-68 PMID: 16169070
  94. Genome-wide analysis of gene expression regulated by the calcineurin/Crz1p signaling pathway in Saccharomyces cerevisiae.
    J Biol Chem. 2002 Aug 23;277(34):31079-88 PMID: 12058033
  95. Error and attack tolerance of complex networks
    Nature. 2000 Jul 27;406(6794):378-82 PMID: 10935628
  96. Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile.
    Cell. 2005 Nov 4;123(3):507-19 PMID: 16269340
  97. The transcriptional program of sporulation in budding yeast.
    Science. 1998 Oct 23;282(5389):699-705 PMID: 9784122
  98. Discovery of biological networks from diverse functional genomic data.
    Genome Biol. 2005;6(13):R114 PMID: 16420673
  99. 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 U S A. 2000 Feb 1;97(3):1143-7 PMID: 10655498
  100. An exponential core in the heart of the yeast protein interaction network.
    Mol Biol Evol. 2005 Mar;22(3):421-5 PMID: 15496552
  101. Collective dynamics of 'small-world' networks.
    Nature. 1998 Jun 4;393(6684):440-2 PMID: 9623998
  102. Modeling interactome: scale-free or geometric?
    Bioinformatics. 2004 Dec 12;20(18):3508-15 PMID: 15284103
  103. The yeast protein interaction network evolves rapidly and contains few redundant duplicate genes.
    Mol Biol Evol. 2001 Jul;18(7):1283-92 PMID: 11420367
  104. Systematic interpretation of genetic interactions using protein networks.
    Nat Biotechnol. 2005 May;23(5):561-6 PMID: 15877074
  105. Essential genes are more evolutionarily conserved than are nonessential genes in bacteria.
    Genome Res. 2002 Jun;12(6):962-8 PMID: 12045149
  106. The synthetic genetic interaction spectrum of essential genes.
    Nat Genet. 2005 Oct;37(10):1147-52 PMID: 16155567
Article Info
Journal
Journal of biology
Abbr.
J Biol
ISSN
1475-4924
Published
2006-00-00
Epub
2006-00-08
Pages
11
Language
English
Region
England
NLM ID
101147570
PMCID
PMC1561585
Subset
IM
Corrections
CommentIn
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