BACKGROUND: Despite the continuous production of genome sequence for a number of 
organisms, reliable, comprehensive, and cost effective gene prediction remains 
problematic. This is particularly true for genomes for which there is not a 
large collection of known gene sequences, such as the recently published chicken 
genome. We used the chicken sequence to test comparative and homology-based 
gene-finding methods followed by experimental validation as an effective genome 
annotation method.
RESULTS: We performed experimental evaluation by RT-PCR of three different 
computational gene finders, Ensembl, SGP2 and TWINSCAN, applied to the chicken 
genome. A Venn diagram was computed and each component of it was evaluated. The 
results showed that de novo comparative methods can identify up to about 700 
chicken genes with no previous evidence of expression, and can correctly extend 
about 40% of homology-based predictions at the 5' end.
CONCLUSIONS: De novo comparative gene prediction followed by experimental 
verification is effective at enhancing the annotation of the newly sequenced 
genomes provided by standard homology-based methods.