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Gene Expression Profiling of Scleroderma Skin


ABSTRACT: We have analyzed the genome-wide patterns of gene expression with DNA microarrays in skin biopsies from 34 subjects: 17 patients with SSc with diffuse scleroderma (dSSc), 7 patients with SSc with limited scleroderma (lSSc), 3 patients with morphea and 6 healthy controls. In total, 61 skin biopsies were analyzed. The addition of 14 technical replicates resulted in a total of 75 microarray hybridizations. The Intrinsic_scleroderma_genes.txt supplementary file lists the 995 genes with the most consistent expression between each forearm-back pair and technical replicates, but with the highest variance across all samples analyzed. An intrinsic gene identifier algorithm was used to select a set of intrinsic scleroderma genes. A total of 34 experimental groups were defined, each representing the 34 different subjects in our study. Replicate hybridizations for a given patient were assigned to the same experimental group. Each gene was analyzed and assigned a score that is inversely related to how intrinsic the gene's expression is across the samples analyzed. The analysis was repeated on randomized data in order to estimate a False Discovery Rate (FDR). An intrinsic score of 0.3 selected 995 genes with an FDR of 4% (39 ± 7 genes) while retaining reproducible clustering of technical replicates. Keywords: global gene expression profiling using Agilent Whole Human genome oligo arrays common reference design; we used Universal Human Reference RNA (Stratagene) as our reference for every array; For every hybridization sample RNA was always labeled with Cy3, and reference RNA was always labeled with Cy5; Microarray hybridizations were performed for 61 RNA samples from 34 subjects resulting 61 hybridizations. Fourteen replicate hybridizations were added, resulting in a total of 75 microarray hybridizations.

ORGANISM(S): Homo sapiens

SUBMITTER: Michael Whitfield 

PROVIDER: E-GEOD-9285 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Molecular subsets in the gene expression signatures of scleroderma skin.

Milano Ausra A   Pendergrass Sarah A SA   Sargent Jennifer L JL   George Lacy K LK   McCalmont Timothy H TH   Connolly M Kari MK   Whitfield Michael L ML  

PloS one 20080716 7


<h4>Background</h4>Scleroderma is a clinically heterogeneous disease with a complex phenotype. The disease is characterized by vascular dysfunction, tissue fibrosis, internal organ dysfunction, and immune dysfunction resulting in autoantibody production.<h4>Methodology and findings</h4>We analyzed the genome-wide patterns of gene expression with DNA microarrays in skin biopsies from distinct scleroderma subsets including 17 patients with systemic sclerosis (SSc) with diffuse scleroderma (dSSc),  ...[more]

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