Probe Level Analysis of Affymetrix Microarray Data

The analysis of Affymetrix GeneChip® data is a complex, multistep process. Most often, methodscondense the multiple probe level intensities into single probeset level measures (such as RobustMulti-chip Average (RMA), dChip and Microarray Suite version 5.0 (MAS5)), which are thenfollowed by application of statistical tests to determine which genes are differentially expressed. An alternative approach is a probe-level analysis, which tests for differential expression directly using the probe-level data. Probe-level models offer the potential advantage of more accurately capturing sources of variation in microarray experiments. However, this has not been thoroughly investigated, since current research efforts have largely focused on the development of improved expression summary methods. This research project will review current approaches to analysis of probe-level data and discuss extensions of two examples, the S-Score and the Random Variance Model (RVM). The S-Score is a probe-level algorithm based on an error model in which the detected signal is proportional to the probe pair signal for highly expressed genes, but approaches a background level (rather than 0) for genes with low levels of expression. Initial results with the S-Score have been promising, but the method has been limited to two-chip comparisons. This project presents extensions to the S-Score that permit comparisons of multiple chips and "borrowing" of information across probes to increase statistical power. The RVM is a probeset-level algorithm that models the variance of the probeset intensities as a random sample from a common distribution to "borrow" information across genes. This project presents extensions to the RVM for probe-level data, using multivariate statistical theory to model the covariance among probes in a probeset. Both of these methods show the advantages of probe-level, rather than probeset-level, analysis in detecting differential gene expression for Afymetrix GeneChip data. Future research will focus on refining the probe-level models of both the S-Score and RVM algorithms to increase the sensitivity and specificity of microarray experiments.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biostatistics

Year dc:date.available

2008

Author dc:creator

• Kennedy, Richard Ellis

Contributors dc:contributor

• Dr. Kellie J. Archer

• covariance
• probe
• Affymetrix
• microarray
• Biostatistics
• Physical Sciences and Mathematics
• Statistics and Probability

Statement dc:rights

• © The Author

Identifier

https://scholarscompass.vcu.edu/etd/978

OAI identifier oai:identifier

oai:scholarscompass.vcu.edu:etd-1977