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

DOI10.1214/10-AOAS389MaRDI QIDQ542489zbMATH OpenOpenAlexWikidataFDO

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)

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

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)

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.

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Cites work

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

Cited in

(2)

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

Describes a project that uses

Uses Software

• MADS
• ANOSVA

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