The functional landscape of mouse gene expression.
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.
Zhang
Wen
W
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.
Morris
Quaid D
QD
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.
Chang
Richard
R
Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Shai
Ofer
O
Department of Electrical and Computer Engineering, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Bakowski
Malina A
MA
Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Mitsakakis
Nicholas
N
Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Mohammad
Naveed
N
Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Robinson
Mark D
MD
Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Zirngibl
Ralph
R
Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Somogyi
Eszter
E
Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Laurin
Nancy
N
Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Eftekharpour
Eftekhar
E
Department of Surgery, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Sat
Eric
E
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
Grigull
Jörg
J
Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Pan
Qun
Q
Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Peng
Wen-Tao
WT
Banting and Best Department of Medical Research, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Krogan
Nevan
N
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.
Greenblatt
Jack
J
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.
Fehlings
Michael
M
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.
van der Kooy
Derek
D
Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Aubin
Jane
J
Department of Medical Genetics and Microbiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Bruneau
Benoit G
BG
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.
Rossant
Janet
J
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.
Blencowe
Benjamin J
BJ
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.
Frey
Brendan J
BJ
Department of Electrical and Computer Engineering, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Hughes
Timothy R
TR
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.
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
D012333:RNA, Messenger