Open Access Highly Accessed Research article

A chemokine gene expression signature derived from meta-analysis predicts the pathogenicity of viral respiratory infections

Stewart T Chang1, Nicolas Tchitchek2, Debashis Ghosh3, Arndt Benecke2 and Michael G Katze14*

Author Affiliations

1 Department of Microbiology, University of Washington, Seattle WA, USA

2 Institut des Hautes Etudes Scientifiques, Bures-sur-Yvette, France

3 Department of Statistics, Pennsylvania State University, University Park PA, USA

4 Washington National Primate Research Center, Seattle WA, USA

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BMC Systems Biology 2011, 5:202  doi:10.1186/1752-0509-5-202

Published: 22 December 2011

Additional files

Additional file 1:

Figure S1. Hierarchical clustering identifying gene clusters oppositely regulated across various conditions in the compendium. Shown are log2-ratios of intensities in infected to mock-infected samples for genes whose ratios were non-zero across all the measurements in the compendium. The two clusters of interest are boxed in yellow and enumerated to the right of the heat map. Heat maps were generated using the heatmap2 function from the gplots package in R statistical environment with clustering by Euclidean distance and the complete linkage method.

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Additional file 2:

Figure S2. Derivation of digital gene signatures. (A) The 74-gene signature comprised 44 and 30 genes derived from the intersection of four parent gene sets: those up-regulated in HPI ∩ down-regulated in LPI and those down-regulated in HPI ∩ up-regulated in LPI. Each parent gene set was derived using Fisher's summary statistic following one-tailed t-tests on each biological condition in the compendium. Each intersection was found to represent a significantly larger proportion of its two parent gene sets than expected by chance (as determined by hypergeometric test, p < 0.05). (B) Module map resulting from applying Genomica to the log-ratio compendium. Module up-regulation in a given condition is indicated in red, and module down-regulation in green. (C) Expression of Module 5 comprising 265 genes. HPI-associated arrays are indicated in purple, LPI-associated arrays in blue. Values shown are consistent with the overall pattern of module expression in those arrays in which the module is significantly expressed. Module 5 completely subsumed Module 6 and was used in subsequent analysis.

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Additional file 3:

Table S1. Digital signature genes by Fisher's summary-statistic.

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Table S2. Digital signature genes by module-mapping.

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Table S3. Analog signature genes by fold change-based z-test.

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Additional file 6:

Figure S3. Characterization of the 74-gene digital signature of pathogenicity by networks of known interactions. Genes present in the signature are indicated in gray shapes. (A) For the 44-gene subset up-regulated in HPIs and down-regulated in LPIs. (B) For the 30-gene subset down-regulated in HPIs and up-regulated in LPIs.

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Additional file 7:

Figure S4. Expression levels of select analog signature genes in HPI, MPI, and LPI conditions. These genes met the criterion of being expressed from greatest to least or from least to greatest (inset) by pathogenicity. Error bars represent standard errors of the means across all HPI, MPI, or LPI conditions in the compendium.

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