Technical Note

Calculation of Splicing Potential from the Alternative Splicing Mutation Database

Jason M Bechtel¹ , Preeti Rajesh^2,3 , Irina Ilikchyan⁴ , Ying Deng⁵ , Pankaj K Mishra² , Qi Wang⁵ , Xiaochun Wu² , Kirill A Afonin⁴ , William E Grose² , Ye Wang⁴ , Sadik Khuder^1,6 and Alexei Fedorov^1,6

¹  Program in Bioinformatics and Proteomics/Genomics, University of Toledo Health Science Campus, Toledo, Ohio 43614, USA

²  Dept. of Medical Microbiology and Immunology, University of Toledo Health Science Campus, Toledo, Ohio 43614, USA

³  Dept. of Basic Pharmaceutical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, South Carolina 29208, USA

⁴  Department of Biological Sciences, Bowling Green State University, Bowling Green, Ohio 43403, USA

⁵  College of Engineering, University of Toledo, Toledo, Ohio 43606, USA

⁶  Dept. of Medicine, University of Toledo Health Science Campus, Toledo, Ohio 43614, USA

author email corresponding author email

BMC Research Notes 2008, 1:4doi:10.1186/1756-0500-1-4

Published:	26 February 2008

Abstract

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.

Conclusion

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.