Predicting internal exons by oligonucleotide composition and discriminant analysis of spliceable open reading frames

Abstract

A new method which predicts internal exon sequences in human DNA has been developed. The method is based on a splice site prediction algorithm that uses the linear discriminant function to combine information about significant triplet frequencies of various functional parts of splice site regions and preferences of oligonucleotides in protein coding and intron regions. The accuracy of our splice site recognition function is 97% for donor splice sites and 96% for acceptor splice sites. For exon prediction, we combine in a discriminant function the characteristics describing the 5'-intron region, donor splice site, coding region, acceptor splice site and 3'-intron region for each open reading frame flanked by GT and AG base pairs. The accuracy of precise internal exon recognition on a test set of 451 exon and 246693 pseudoexon sequences is 77% with a specificity of 79%. The recognition quality computed at the level of individual nucleotides is 89% for exon sequences and 98% for intron sequences. This corresponds to a correlation coefficient for exon prediction of 0.87. The precision of this approach is better than other methods and has been tested on a larger data set. We have also developed a means for predicting exon-exon junctions in cDNA sequences, which can be useful for selecting optimal PCR primers.