Technical Note

Calculation of Splicing Potential from the Alternative Splicing Mutation Database

Jason M Bechtel , Preeti Rajesh , Irina Ilikchyan , Ying Deng , Pankaj K Mishra , Wang Qi , Xiaochun Wu , Kirill A Afonin , William E Grose , Wang Ye , Sadik Khuder and Alexei Fedorov

BMC Research Notes 2008, 1:4

Published:	26 February 2008

Abstract (provisional)

Background

The Alternative Splicing Mutation Database (ASMD) presents a collection of all known mutations inside human exons which affect splicing enhancers and silencers and cause changes in the alternative splicing pattern of the corresponding genes.

Findings

An algorithm was developed to derive a Splicing Potential (SP) table from the ASMD information. This table characterizes the influence of each oligonucleotide on the splicing effectiveness of the exon containing it. If the SP value for an oligonucleotide is positive, it promotes exon retention, while negative SP values mean the sequence favors exon skipping. The merit of the SP approach is the ability to separate splicing signals from a wide range of sequence motifs enriched in exonic sequences that are attributed to protein-coding properties and/or translation efficiency. Due to its direct derivation from observed splice site selection, SP has an advantage over other computational approaches for predicting alternative splicing.

Conclusions

We show that a vast majority of known exonic splicing enhancers have highly positive cumulative SP values, while known splicing silencers have core motifs with strongly negative cumulative SP values. Our approach allows for computation of the cumulative SP value of any sequence segment and, thus, gives researchers the ability to measure the possible contribution of any sequence to the pattern of splicing.