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 P₁, . . . , P_a and N₁, . . . , 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 s₁, . . . , s_a of P₁, . . . , P_a such that s₁, . . . ,s_a are similar to each other to some extent, and such that any substrings of N₁, . . . , N_b are not similar to s₁, . . . , 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.