Searching for Regulatory Elements of Alternative Splicing Events Using Phylogenetic Footprinting
We consider the problem of finding candidates for regulatory elements of alternative splicing events from orthologous genes, using phylogenetic footprinting. The problem is formulated as follows: We are given orthologous sequences P 1,...,P a and N 1,...,N b from a + b different species, and a phylogenetic tree relating these species. Assume that for i=1,...,a, P i is known to have some alternative splicing events, although N j does not have any alternative splicing events. Our objective is to find all sets of substrings s 1,...,s a of P 1,...,P a such that s 1,...,s a are similar to each other to some extent, and such that any substrings of N 1,...,N b are not similar to s 1,...,s a . To this aim, we have modified the phylogenetic footprinting algorithm given by Blanchette et al. to solve our problem. We report the results of our preliminary computational experiments on several sets of orthologous genes of the five species, H.sapiens, M.musculus, D.melanogaster, C.elegans, and A.thaliana. It is interesting that many of the substrings selected by our algorithm from the coding sequences of H.sapiens are substrings in the intronic sequences flanking the alternatively spliced exons of the coding sequence. This result implies that regulatory elements of alternative splicing events would be located in intronic sequences flanking the alternatively spliced exons.
KeywordsAlternative Splice Regulatory Element Orthologous Gene Intronic Sequence Dynamic Programming Algorithm
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