SST versus EST in gene recognition.

The expressed sequence tag (EST) data provide a powerful tool for identification of transcribed DNA sequences. However, as EST are relatively short, many exons are poorly covered by EST, thus reducing the utility of EST data. Recently, signature sequence tag (SST) fingerprints were proposed as an alternative to EST fingerprints. Given a fingerprint set of probes, SST of a clone is a subset of probes from the fingerprint set that hybridize with the clone. We demonstrate that besides being a powerful technique for screening cDNA libraries, SST technology provides for very accurate gene predictions. Even with a small fingerprint set (600-800 probes), SST-based gene recognition outperforms many conventional and EST-based methods. The increase in the size of the fingerprint set to 1500 probes provides almost perfect gene recognition. Even more importantly, SST-based gene predictions miss very few exons and, therefore, provide an opportunity to bypass the cDNA sequencing step on the way from finished genomic sequence to mutation detection in gene-hunting projects. Because SST data can be obtained in a highly parallel and inexpensive way, SST technology has a potential of complementing EST technology for gene hunting.