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Letter
Nature Genetics  37, 991 - 996 (2005)
Published online: 28 August 2005; | doi:10.1038/ng1630

Genome-wide analysis of mouse transcripts using exon microarrays and factor graphs

Brendan J Frey1, 2, 6, Naveed Mohammad2, 6, Quaid D Morris1, 2, 6, Wen Zhang2, 3, 6, Mark D Robinson1, 2, Sanie Mnaimneh2, Richard Chang2, Qun Pan2, Eric Sat4, Janet Rossant3, 4, Benoit G Bruneau3, 5, Jane E Aubin3, Benjamin J Blencowe2, 3 & Timothy R Hughes2, 3

1  Electrical and Computer Engineering, University of Toronto, 10 King's College Rd., Toronto, Ontario M5S 3G4, Canada.

2  Banting and Best Department of Medical Research, University of Toronto, 112 College St., Toronto, Ontario M5G 1L6, Canada.

3  Medical Genetics and Microbiology, University of Toronto, 1 King's College Ct., Toronto, Ontario M5S 3G4, Canada.

4  Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.

5  The Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada.

6  These authors contributed equally to this work.

Correspondence should be addressed to Timothy R Hughes t.hughes@utoronto.ca or Benjamin J Blencowe frey@psi.toronto.edu

Recent mammalian microarray experiments detected widespread transcription and indicated that there may be many undiscovered multiple-exon protein-coding genes. To explore this possibility, we labeled cDNA from unamplified, polyadenylation-selected RNA samples from 37 mouse tissues to microarrays encompassing 1.14 million exon probes. We analyzed these data using GenRate, a Bayesian algorithm that uses a genome-wide scoring function in a factor graph to infer genes. At a stringent exon false detection rate of 2.7%, GenRate detected 12,145 gene-length transcripts and confirmed 81% of the 10,000 most highly expressed known genes. Notably, our analysis showed that most of the 155,839 exons detected by GenRate were associated with known genes, providing microarray-based evidence that most multiple-exon genes have already been identified. GenRate also detected tens of thousands of potential new exons and reconciled discrepancies in current cDNA databases by 'stitching' new transcribed regions into previously annotated genes.


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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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