Latent rank change detection for analysis of splice-junction microarrays with nonlinear effects

DOI10.1214/10-AOAS389zbMATH Open1220.62134arXiv1104.3016OpenAlexW2012841853WikidataQ36538871 ScholiaQ36538871MaRDI QIDQ542489FDOQ542489

Authors: Lee Ann Zarzabal, Tarea Burton, Suzanne Burns, Mari Sogayar, Luiz O. F. Penalva, Jonathan A. Gelfond 

Publication date: 10 June 2011

Published in: The Annals of Applied Statistics (Search for Journal in Brave)

Abstract: Alternative splicing of gene transcripts greatly expands the functional capacity of the genome, and certain splice isoforms may indicate specific disease states such as cancer. Splice junction microarrays interrogate thousands of splice junctions, but data analysis is difficult and error prone because of the increased complexity compared to differential gene expression analysis. We present Rank Change Detection (RCD) as a method to identify differential splicing events based upon a straightforward probabilistic model comparing the over- or underrepresentation of two or more competing isoforms. RCD has advantages over commonly used methods because it is robust to false positive errors due to nonlinear trends in microarray measurements. Further, RCD does not depend on prior knowledge of splice isoforms, yet it takes advantage of the inherent structure of mutually exclusive junctions, and it is conceptually generalizable to other types of splicing arrays or RNA-Seq. RCD specifically identifies the biologically important cases when a splice junction becomes more or less prevalent compared to other mutually exclusive junctions. The example data is from different cell lines of glioblastoma tumors assayed with Agilent microarrays.

Full work available at URL: https://arxiv.org/abs/1104.3016

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zbMATH Keywords

microarrayalternative splicinggene expression analysis

Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10) Biochemistry, molecular biology (92C40)

Cites Work

• Statistical significance for genomewide studies
• Experimental design for gene expression microarrays

Cited In (2)

• Singular value decomposition-based alternative splicing detection
• Searching for alternative splicing with a joint model on probe measurability and expression intensities

Uses Software

• ANOSVA
• MADS

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