SeeSite: Efficiently Finding Co-occurring Splice Sites and Exon Splicing Enhancers

The problem of identifying splice sites consists of two sub-problems: finding their boundaries, and characterizing their sequence markers. Other splicing elements—including, enhancers and silencers—that occur in the intronic and exonic regions play an important role in splicing activity. Existing methods for detecting splicing elements are limited to finding either splice sites or enhancers and silencers, even though these elements are well-known to co-occur. We introduce SeeSite, an efficient and accurate tool for detecting splice sites and their complementary exon splicing enhancers (ESEs). SeeSite has three stages: graph construction, finding dense subgraphs, and recovering splice sites and ESEs along with their consensus. The third step involves solving Consensus Sequence with Outliers, an NP-complete string clustering problem. We prove that our algorithm for this problem outputs near-optimal solutions in polynomial time. Using SeeSite we demonstrate that ESEs are preferentially associated with weaker splice sites, and splice sites of a certain canonical form co-occur with specific ESEs.