ASmodeler is
a novel web-based utility to find gene models of alternative splicing (AS)
events from genomic alignment of mRNA and ESTs. Alternative splicing is an
important mechanism of modulating gene function, and it is directly related to
many diseases. We provide a fast and versatile web program for AS modeling.
Input
sequences are aligned against the genome map using BLAT program developed by J.
Kent at UCSC. Suspicious alignments with noncanonical introns and with tiny
exons are corrected using dynamic programming (Sim4). BLAT-Sim4 combination
gives fast and reliable genomic alignments. Aligned exons are analyzed in a
graph theoretic fashion. Paths along the compatible exons are constructed from
the directed acyclic graph (DAG) of exons. Standard depth-first search (DFS)
algorithm produces all possible gene models of AS events. mRNA and ESTs are
grouped for each gene model as a supporting evidence. ASmodeler is essentially
a transcript assembly program as well as an EST clustering utility.
Web-implementation
of ASmodeler supports various user options. Many alignment criteria, such as
alignment program, method of dealing with multiple hits, percent identity and
alignment coverage filtering, are under user control. One can select the best
alignment in whole genome or in one chromosome. Input sequences can be aligned
against a specific genomic region in various ways. Furthermore, well-known gene
predictions (ex. Ensembl, Fgenesh++, Acembly, Genscan and etc) can be included
before generating gene models. Three genome maps – human, mouse, and rat – are
currently being supported at http://genome.ewha.ac.kr/ASmodeler/.
ASmodeler can
be applied as a method of comparative gene modeling. For example, homologous
sequences from other species can be included to search for putative AS variants
in the human genome.
50-word
Abstract: