title: Comprehensive exon array data processing method for quantitative analysis of alternative spliced variants.
abstract: Alternative splicing of pre-mRNA generates protein diversity. Dysfunction of splicing machinery and expression of specific transcripts has been linked to cancer progression and drug response. Exon microarray technology enables genome-wide quantification of expression levels of the majority of exons and facilitates the discovery of alternative splicing events. Analysis of exon array data is more challenging than the analysis of gene expression data and there is a need for reliable quantification of exons and alternatively spliced variants. We introduce a novel, computationally efficient methodology, Multiple Exon Array Preprocessing (MEAP), for exon array data pre-processing, analysis and visualization. We compared MEAP with existing pre-processing methods, and validation of six exons and two alternatively spliced variants with qPCR corroborated MEAP expression estimates. Analysis of exon array data from head and neck squamous cell carcinoma (HNSCC) cell lines revealed several transcripts associated with 11q13 amplification, which is related with decreased survival and metastasis in HNSCC patients. Our results demonstrate that MEAP produces reliable expression values at exon, alternatively spliced variant and gene levels, which allows generating novel experimentally testable predictions.
authors: Research Programs Unit, Genome-Scale Biology and Institute of Biomedicine, Biochemistry and Developmental Biology, 00014 University of Helsinki, Finland.
authors: Ping
authors: P
authors: Chen
authors: Tatiana
authors: T
authors: Lepikhova
authors: Yizhou
authors: Y
authors: Hu
authors: Outi
authors: O
authors: Monni
authors: Sampsa
authors: S
authors: Hautaniemi
mesh_terms: D017398:Alternative Splicing; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D005091:Exons; D020869:Gene Expression Profiling / Q000379:methods*; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020033:Protein Isoforms / Q000032:analysis* / Q000235:genetics / Q000378:metabolism
chemical_list: D020033:Protein Isoforms