title: Comprehensive curation and analysis of global interaction networks in Saccharomyces cerevisiae.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto ON M5G 1X5, Canada.
authors.forename: Teresa
authors.initials: T
authors.lastname: Reguly
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto ON M5G 1X5, Canada.
authors.forename: Ashton
authors.initials: A
authors.lastname: Breitkreutz
authors.affiliation: 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.
authors.forename: Lorrie
authors.initials: L
authors.lastname: Boucher
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto ON M5G 1X5, Canada.
authors.forename: Bobby-Joe
authors.initials: BJ
authors.lastname: Breitkreutz
authors.affiliation: Department of Bioengineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA.
authors.forename: Gary C
authors.initials: GC
authors.lastname: Hon
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Washington Road, Princeton, NJ 08544, USA.|Department of Computer Science, Princeton University, NJ 08544, USA.
authors.forename: Chad L
authors.initials: CL
authors.lastname: Myers
authors.affiliation: 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.
authors.forename: Ainslie
authors.initials: A
authors.lastname: Parsons
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, Toronto ON M5G 1L6, Canada.
authors.forename: Helena
authors.initials: H
authors.lastname: Friesen
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Washington Road, Princeton, NJ 08544, USA.
authors.forename: Rose
authors.initials: R
authors.lastname: Oughtred
authors.affiliation: 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.
authors.forename: Amy
authors.initials: A
authors.lastname: Tong
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto ON M5G 1X5, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Stark
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, Toronto ON M5G 1L6, Canada.
authors.forename: Yuen
authors.initials: Y
authors.lastname: Ho
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Washington Road, Princeton, NJ 08544, USA.
authors.forename: David
authors.initials: D
authors.lastname: Botstein
authors.affiliation: 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.
authors.forename: Brenda
authors.initials: B
authors.lastname: Andrews
authors.affiliation: 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.
authors.forename: Charles
authors.initials: C
authors.lastname: Boone
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Washington Road, Princeton, NJ 08544, USA.|Department of Computer Science, Princeton University, NJ 08544, USA.
authors.forename: Olga G
authors.initials: OG
authors.lastname: Troyanskya
authors.affiliation: Department of Bioengineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA.
authors.forename: Trey
authors.initials: T
authors.lastname: Ideker
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Washington Road, Princeton, NJ 08544, USA.
authors.forename: Kara
authors.initials: K
authors.lastname: Dolinski
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto ON M5G 1X5, Canada.
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Batada
authors.affiliation: 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.
authors.forename: Mike
authors.initials: M
authors.lastname: Tyers
mesh_terms: D019295:Computational Biology; D025941:Protein Interaction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins