With the availability of a nearly complete sequence of the human genome, 
aligning expressed sequence tags (EST) to the genomic sequence has become a 
practical and powerful strategy for gene prediction. Elucidating gene structure 
is a complex problem requiring the identification of splice junctions, gene 
boundaries, and alternative splicing variants. We have developed a software 
tool, Transcript Assembly Program (TAP), to delineate gene structures using 
genomically aligned EST sequences. TAP assembles the joint gene structure of the 
entire genomic region from individual splice junction pairs, using a novel 
algorithm that uses the EST-encoded connectivity and redundancy information to 
sort out the complex alternative splicing patterns. A method called 
polyadenylation site scan (PASS) has been developed to detect poly-A sites in 
the genome. TAP uses these predictions to identify gene boundaries by segmenting 
the joint gene structure at polyadenylated terminal exons. Reconstructing 1007 
known transcripts, TAP scored a sensitivity (Sn) of 60% and a specificity (Sp) 
of 92% at the exon level. The gene boundary identification process was found to 
be accurate 78% of the time. also reports alternative splicing patterns in EST 
alignments. An analysis of alternative splicing in 1124 genic regions suggested 
that more than half of human genes undergo alternative splicing. Surprisingly, 
we saw an absolute majority of the detected alternative splicing events affect 
the coding region. Furthermore, the evolutionary conservation of alternative 
splicing between human and mouse was analyzed using an EST-based approach. (See 
http://stl.wustl.edu/~zkan/TAP/)