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Vol. 10, Issue 4, 529-538, April 2000

METHODS
Genie---Gene Finding in Drosophila melanogaster

Martin G. Reese,1,2,4 David Kulp,2 Hari Tammana,2 and David Haussler2,3

1 Berkeley Drosophila Genome Project, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200 USA; 2 Neomorphic, Inc., Berkeley, California 94710 USA; 3 Computer Science Department, University of California, Santa Cruz, California 95064 USA

A hidden Markov model-based gene-finding system called Genie was applied to the genomic Adh region in Drosophila melanogaster as a part of the Genome Annotation Assessment Project (GASP). Predictions from three versions of the Genie gene-finding system were submitted, one based on statistical properties of coding genes, a second included EST alignment information, and a third that integrated protein sequence homology information. All three programs were trained on the provided Drosophila training data. In addition, promoter assignments from an integrated neural network were submitted. The gene assignments overlapped >90% of the 222 annotated genes and 26 possibly novel genes were predicted, of which some might be overpredictions. The system correctly identified the exon boundaries of 70% of the exons in cDNA-confirmed genes and 77% of the exons with the addition of EST sequence alignments. The best of the three Genie submissions predicted 19 of the annotated 43 gene structures entirely correct (44%). In the promoter category, only 30% of the transcription start sites could be detected, but by integrating this program as a sensor into Genie the false-positive rate could be dropped to 1/16,786 (0.006%). The results of the experiment on the long contiguous genomic sequence revealed some problems concerning gene assembly in Genie. The results were used to improve the system. We show that Genie is a robust hidden Markov model system that allows for a generalized integration of information from different sources such as signal sensors (splice sites, start codon, etc.), content sensors (exons, introns, intergenic) and alignments of mRNA, EST, and peptide sequences. The assessment showed that Genie could effectively be used for the annotation of complete genomes from higher organisms.

4 Corresponding author.

10:529-538 ©2000 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/00 $5.00
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