Different effects of the probe summarization algorithms PLIER and RMA on high-level analysis of Affymetrix exon arrays

Background: Alternative splicing is an important mechanism that increases protein diversity and functionality in higher eukaryotes. Affymetrix exon arrays are a commercialized platform used to detect alternative splicing on a genome-wide scale. Two probe summarization algorithms, PLIER (Probe Logarithmic Intensity Error) and RMA (Robust Multichip Average), are commonly used to compute gene-level and exon-level expression values. However, a systematic comparison of these two algorithms on their effects on high-level analysis of the arrays has not yet been reported. Results: In this study, we showed that PLIER summarization led to over-estimation of gene-level expression changes, relative to exon-level expression changes, in two-group comparisons. Consequently, it led to detection of substantially more skipped exons on up-regulated genes, as well as substantially more included (i.e., non-skipped) exons on downregulated genes. In contrast, this bias was not observed for RMA-summarized da...

• Type: Journal
• Year: 2010
• Where: BMCBI
• Authors: Yi Qu, Fei He, Yuchen Chen
• Keywords: Affymetrix Exon, Alternative Splicing, BMCBI 2010, Exon-level Expression