Query large scale microarray compendium datasets using a model-based bayesian approach with variable selection.
In microarray gene expression data analysis, it is often of interest to identify genes that share similar expression profiles with a particular gene such as a key regulatory protein. Multiple studies have been conducted using various correlation measures to identify co-expressed genes. While working well for small datasets, the heterogeneity introduced from increased sample size inevitably reduces the sensitivity and specificity of these approaches. This is because most co-expression relationships do not extend to all experimental conditions. With the rapid increase in the size of microarray datasets, identifying functionally related genes from large and diverse microarray gene expression datasets is a key challenge. We develop a model-based gene expression query algorithm built under the Bayesian model selection framework. It is capable of detecting co-expression profiles under a subset of samples/experimental conditions. In addition, it allows linearly transformed expression patterns to be recognized and is robust against sporadic outliers in the data. Both features are critically important for increasing the power of identifying co-expressed genes in large scale gene expression datasets. Our simulation studies suggest that this method outperforms existing correlation coefficients or mutual information-based query tools. When we apply this new method to the Escherichia coli microarray compendium data, it identifies a majority of known regulons as well as novel potential target genes of numerous key transcription factors.
Hu
Ming
M
Department of Biostatistics, Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.
Qin
Zhaohui S
ZS
D000465:Algorithms; D001499:Bayes Theorem; D030541:Databases, Genetic; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012372:ROC Curve; D012680:Sensitivity and Specificity