Expression profiles of switch-like genes accurately classify tissue and infectious disease phenotypes in model-based classification

Michael Gormley,Aydin Tozeren

doi:10.1186/1471-2105-9-486

Abstract

BackgroundLarge-scale compilation of gene expression microarray datasets across diverse biological phenotypes provided a means of gathering a priori knowledge in the form of identification and annotation of bimodal genes in the human and mouse genomes. These switch-like genes consist of 15% of known human genes, and are enriched with genes coding for extracellular and membrane proteins. It is of interest to determine the prediction potential of bimodal genes for class discovery in large-scale datasets.ResultsUse of a model-based clustering algorithm accurately classified more than 400 microarray samples into 19 different tissue types on the basis of bimodal gene expression. Bimodal expression patterns were also highly effective in differentiating between infectious diseases in model-based clustering of microarray data. Supervised classification with feature selection restricted to switch-like genes also recognized tissue specific and infectious disease specific signatures in independent test datasets reserved for validation. Determination of "on" and "off" states of switch-like genes in various tissues and diseases allowed for the identification of activated/deactivated pathways. Activated switch-like genes in neural, skeletal muscle and cardiac muscle tissue tend to have tissue-specific roles. A majority of activated genes in infectious disease are involved in processes related to the immune response.ConclusionSwitch-like bimodal gene sets capture genome-wide signatures from microarray data in health and infectious disease. A subset of bimodal genes coding for extracellular and membrane proteins are associated with tissue specificity, indicating a potential role for them as biomarkers provided that expression is altered in the onset of disease. Furthermore, we provide evidence that bimodal genes are involved in temporally and spatially active mechanisms including tissue-specific functions and response of the immune system to invading pathogens.

Highlights

Large-scale compilation of gene expression microarray datasets across diverse biological phenotypes provided a means of gathering a priori knowledge in the form of identification and annotation of bimodal genes in the human and mouse genomes
Classification was based either on the expression of the complete list of 1265 human switch-like genes (Figure 1 Column 1) or a subset of this list containing 300 bimodal genes translated into extracellular matrix or plasma membrane proteins (Figure 1 Column 2)
Right column: classification with 300 bimodal genes translated into extracellular matrix or plasma membrane proteins

Summary

Introduction

Large-scale compilation of gene expression microarray datasets across diverse biological phenotypes provided a means of gathering a priori knowledge in the form of identification and annotation of bimodal genes in the human and mouse genomes. These switch-like genes consist of 15% of known human genes, and are enriched with genes coding for extracellular and membrane proteins. Genome-wide screening of expression profiles has provided an expansive perspective on gene regulation in health and disease. We have identified and annotated genes with switch-like expression profiles in the mouse and human, using large (page number not for citation purposes). Given the variable expression of switch-like genes, they may provide a viable candidate gene set for the detection of clinically relevant expression signatures in a feature space with reduced dimensionality

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Discussion

Conclusion