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Genomics Inform > Volume 4(1); 2006 > Article
Deducing Isoform Abundance from Exon Junction Microarray.
Po Ra Kim, S June Oh, Sang Hyuk Lee
1Bioinformatics Team, IT-BT group, Electronics and Telecommunications Research Institute, Daejeon, Korea.
2Department of Pharmacology & Pharmacogenomics Research Center, College of Medicine, Inje University, Pusan, Korea.
3Division of Molecular Life Sciences, Ewha Womans University, Seoul, Korea.
Alternative splicing (AS) is an important mechanism of producing transcriptome diversity and microarray techniques are being used increasingly to monitor the splice variants. There exist three types of microarrays interrogating AS events-junction, exon, and tiling arrays. Junction probes have the advantage of monitoring the splice site directly. Johnson et al., performed a genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays (Science 302:2141-2144, 2003), which monitored splicing at every known exon-exon junctions for more than 10,000 multi-exon human genes in 52 tissues and cell lines. Here, we describe an algorithm to deduce the relative concentration of isoforms from the junction array data. Non-negative Matrix Factorization (NMF) is applied to obtain the transcript structure inferred from the expression data. Then we choose the transcript models consistent with the ECgene model of alternative splicing which is based on mRNA and EST alignment. The probe-transcript matrix is constructed using the NMF-consistent ECgene transcripts, and the isoform abundance is deduced from the non-negative least squares (NNLS) fitting of experimental data. Our method can be easily extended to other types of microarrays with exon or junction probes.
Keywords: Alternative Splicing; Junction Microarray; Nonnegative Matrix Factorization (NMF); Non-Negative Least Squares (NNLS)
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