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Gene expression signatures in scleroderma.
4,149 probes that changed at least 2-fold from their median value on at least two microarrays were selected from 75 microarray hybridizations representing 61 biopsies. Probes and microarrays were ordered by 2-dimensional average linkage hierarchical clustering. This clustering shows that the dSSc, lSSc, morphea samples form distinct groups largely stratified by their clinical diagnosis. A. The unsupervised hierarchical clustering dendrogram shows the relationship among the samples using this list of 4,149 probes. Samples names have been color-coded by their clinical diagnosis: dSSc in red, lSSc in orange, morphea and EF in black, and healthy controls (Nor) in green. Forearm (FA) and Back (B) are indicated for each sample. Solid arrows indicate the 14 of 22 forearm-back pairs that cluster next to one another; dashed arrows indicate the additional 3 forearm-back pairs that cluster with only a single sample between them. Technical replicates are indicated by the labels (a), (b) or (c). 9 out of 14 technical replicates cluster immediately beside one another. B. Overview of the gene expression profiles for the 4,149 probes. Each probe has been centered on its median expression value across all samples analyzed. Measurements that are above the median are colored red and those below the median are colored green. The intensity of the color is directly proportional to the fold change. Groups of genes on the right hand side indicated with colored bars are shown in greater detail in panels C–H. C. Immunoglobulin genes expressed highly in a subset of patients with dSSc and in patients with morphea, D. proliferation signature, E. collagen and extracelluar matrix components, F. genes typically associated with the presence of T-lymphocyes and macrophages, G. Genes showing low expression in dSSc, H. Heterogeneous expression cluster that is high in lSSc and a subset of dSSc. In each case only a subset of the genes in each cluster are shown. The precise location of each gene in the cluster can be viewed in Supplemental Figure S1.