This article is part of the supplement: Selected papers from the Seventh Asia-Pacific Bioinformatics Conference (APBC 2009) .

Research

REMAS: a new regression model to identify alternative splicing events from exon array data

Hao Zheng^{* 1} , Xingyi Hang^{* 2} , Ji Zhu³ , Minping Qian¹ , Wubin Qu² , Chenggang Zhang² and Minghua Deng¹

¹LMAM, School of Mathematical Sciences and Center for Theoretical Biology, Peking University, Beijing 100871, PR China

²Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Beijing 100850, PR China

³Department of Statistics, University of Michigan, Ann Arbor, MI 48109-1107, USA

author email corresponding author email* Contributed equally

BMC Bioinformatics 2009, 10(Suppl 1):S18doi:10.1186/1471-2105-10-S1-S18

Published:	30 January 2009

Abstract

Background

Alternative splicing (AS) is an important regulatory mechanism for gene expression and protein diversity in eukaryotes. Previous studies have demonstrated that it can be causative for, or specific to splicing-related diseases. Understanding the regulation of AS will be helpful for diagnostic efforts and drug discoveries on those splicing-related diseases. As a novel exon-centric microarray platform, exon array enables a comprehensive analysis of AS by investigating the expression of known and predicted exons. Identifying of AS events from exon array has raised much attention, however, new and powerful algorithms for exon array data analysis are still absent till now.

Results

Here, we considered identifying of AS events in the framework of variable selection and developed a regression method for AS detection (REMAS). Firstly, features of alternatively spliced exons were scaled by reasonably defined variables. Secondly, we designed a hierarchical model which can represent gene structure and transcriptional influence to exons, and the lasso type penalties were introduced in calculation because of huge variable size. Thirdly, an iterative two-step algorithm was developed to select alternatively spliced genes and exons. To avoid negative effects introduced by small sample size, we ranked genes as parameters indicating their AS capabilities in an iterative manner. After that, both simulation and real data evaluation showed that REMAS could efficiently identify potential AS events, some of which had been validated by RT-PCR or supported by literature evidence.

Conclusion

As a new lasso regression algorithm based on hierarchical model, REMAS has been demonstrated as a reliable and effective method to identify AS events from exon array data.