title: The functional landscape of mouse gene expression.
abstract: BACKGROUND
  Large-scale quantitative analysis of transcriptional co-expression has been used to dissect regulatory networks and to predict the functions of new genes discovered by genome sequencing in model organisms such as yeast. Although the idea that tissue-specific expression is indicative of gene function in mammals is widely accepted, it has not been objectively tested nor compared with the related but distinct strategy of correlating gene co-expression as a means to predict gene function.
  
  
  RESULTS
  We generated microarray expression data for nearly 40,000 known and predicted mRNAs in 55 mouse tissues, using custom-built oligonucleotide arrays. We show that quantitative transcriptional co-expression is a powerful predictor of gene function. Hundreds of functional categories, as defined by Gene Ontology 'Biological Processes', are associated with characteristic expression patterns across all tissues, including categories that bear no overt relationship to the tissue of origin. In contrast, simple tissue-specific restriction of expression is a poor predictor of which genes are in which functional categories. As an example, the highly conserved mouse gene PWP1 is widely expressed across different tissues but is co-expressed with many RNA-processing genes; we show that the uncharacterized yeast homolog of PWP1 is required for rRNA biogenesis.
  
  
  CONCLUSIONS
  We conclude that 'functional genomics' strategies based on quantitative transcriptional co-expression will be as fruitful in mammals as they have been in simpler organisms, and that transcriptional control of mammalian physiology is more modular than is generally appreciated. Our data and analyses provide a public resource for mammalian functional genomics.
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.|Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.|Department of Electrical and Computer Engineering, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Quaid D
authors.initials: QD
authors.lastname: Morris
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Chang
authors.affiliation: Department of Electrical and Computer Engineering, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Ofer
authors.initials: O
authors.lastname: Shai
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Malina A
authors.initials: MA
authors.lastname: Bakowski
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Mitsakakis
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Naveed
authors.initials: N
authors.lastname: Mohammad
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Robinson
authors.affiliation: Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Ralph
authors.initials: R
authors.lastname: Zirngibl
authors.affiliation: Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Eszter
authors.initials: E
authors.lastname: Somogyi
authors.affiliation: Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: Laurin
authors.affiliation: Department of Surgery, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Eftekhar
authors.initials: E
authors.lastname: Eftekharpour
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Sat
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Jörg
authors.initials: J
authors.lastname: Grigull
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Qun
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Peng
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.|Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Nevan
authors.initials: N
authors.lastname: Krogan
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.|Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Jack
authors.initials: J
authors.lastname: Greenblatt
authors.affiliation: Department of Surgery, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.|Division of Cell and Molecular Biology, Toronto Western Research Institute and Krembil Neuroscience Center, 399 Bathurst St., Toronto, ON M5T 2S8, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Fehlings
authors.affiliation: Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Derek
authors.initials: D
authors.lastname: van der Kooy
authors.affiliation: Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Jane
authors.initials: J
authors.lastname: Aubin
authors.affiliation: Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.|The Hospital for Sick Children, 555 University Ave., Toronto, ON M5G 1X8, Canada.
authors.forename: Benoit G
authors.initials: BG
authors.lastname: Bruneau
authors.affiliation: Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.|Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
authors.forename: Janet
authors.initials: J
authors.lastname: Rossant
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.|Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Blencowe
authors.affiliation: Department of Electrical and Computer Engineering, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Frey
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.|Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Hughes
mesh_terms: D000818:Animals; D019295:Computational Biology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023281:Genomics; D051379:Mice / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D015203:Reproducibility of Results; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D012333:RNA, Messenger