Project description:To increase our understanding of psoriasis, we utilized RNA-seq to assay the transcriptomes of lesional psoriatic and normal skin. We sequenced polyadenylated RNA-derived cDNAs from 92 psoriatic and 82 normal punch biopsies, generating an average of ~38 million single-end 80-bp reads per sample. Comparison of 42 samples* examined by both RNA-seq and microarray [GSE13355] revealed marked differences in sensitivity, with transcripts identified only by RNA-seq having much lower expression than those also identified by microarray. RNA-seq identified many more differentially expressed transcripts enriched in immune system processes. Weighted gene co-expression network analysis (WGCNA) revealed multiple modules of coordinately expressed epidermal differentiation genes, overlapping significantly with genes regulated by the long non-coding RNA TINCR, its target gene, staufen-1 (STAU1), the p63 target gene ZNF750, and its target KLF4. Other coordinately expressed modules were enriched for lymphoid and/or myeloid signature transcripts and genes induced by IL-17 in keratinocytes. Dermally-expressed genes were significantly down-regulated in psoriatic biopsies, most likely due to expansion of the epidermal compartment. These results demonstrate the power of WGCNA to elucidate gene regulatory circuits in psoriasis, and emphasize the influence of tissue architecture in both differential expression and co-expression analysis. *The list of 42 samples examined by both RNA-seq and microarray is provided in the 'MAoverlappedsamples.txt'. 92 psoriatic and 82 normal skin samples
Project description:Vitamin D insufficiency may exacerbate non-specific inflammation observed in older adults. Here, we tested the hypothesis that an inflammatory gene signature present in old skin following saline injection (as model for non-specific needle injury) normalizes after oral vitamin D3 supplementation. To define the saline-induced signature, we compared gene expression in skin biopsies taken six hours after saline injection in old adults (≥65 years) to biopsies from unmanipulated skin. We then assessed signature expression in saline-injected skin of old and young adults (<40 years), and in paired samples of old adults before and after oral vitamin D3 supplementation (6400 IU/day for 14 weeks), where median serum 25-hydroxyvitamin D increased from 43 nmol/L (interquartile range 36-53 nmol/L) to 131 nmol/L (interquartile range 115-147 nmol/L). This submission comprises 112 samples from 57 individuals.
Project description:Transcriptome at the site of a 48 hour tuberculin skin test (TST) and saline injection from patients with active TB disease and latent TB infection
Project description:Purpose: To clinically and proteomically profile a fine-needle aspirate biopsy (FNAB) from a single in situ cold thyroid nodule (CTN). Experimental Design: The FNAB lysate was digested with trypsin, and analysed by LC-MSMS on an LTQ Orbitrap Velos. Remaining peptides were separated by reversed-phase chromatography and fractions analysed as technical duplicates. Identified proteins were analysed by Gene Ontology and protein abundance were calculated using the Top3 label-free method. The proteomic data was complemented with ultrasonography and scintigraphy of the thyroid gland; and cytology of the CTN FNAB. Results: Sixty seven and 2,595 non-redundant protein groups (2 unique peptides) were identified from unfractionated and fractionated CTN FNAB, respectively. Label-free protein abundance ranged over 6 orders of magnitude from the most abundant proteins, haemoglobin and thyroglobulin; to the low-abundance protein SON. Many previously-reported markers of thyroid cancer were in the top 23% of the identified proteins. GO analysis revealed high-enrichment for extracellular vesicular exosome and vesicle (cellular component); regulation of biological quality (biological processes); and structural molecule activity (molecular function). Conclusions and Clinical Significance: The CTN was clinically-classified as benign. Proteomic data from FNAB can provide additional diagnostic candidates indicative of benign or cancerous CTN without the need for invasive surgical intervention.
Project description:Biopsies from uninvolved and from lesional skin of 13 patients with plaque-type psoriasis. Based on paired samples, 179 genes were more than 2-fold differentially expressed in lesional skin. Experiment Overall Design: Comparative RNA expression profiles from uninvolved and lesional skin of 13 patients with mild to severe plaque-type psoriasis.
Project description:Gene expression has been proposed as an intermediate phenotype that can increase power in complex trait gene-mapping studies. Psoriasis, an immune-mediated, inflammatory and hyperproliferative disease of the skin and joints, provides an ideal model system to evaluate this paradigm, as conclusive evidence demonstrates that psoriasis has a genetic basis and the disease tissue is readily accessible. To better understand the complex nature of processes in psoriasis, we characterize gene expression profiles in uninvolved and involved skin from affected individuals as well as normal skin from control individuals. Experiment Overall Design: We extracted total RNA from punch biopsies taken from 58 psoriatic patients and 64 normal healthy controls. Two biopsies were taken from each patient; one 6mm punch biopsy was obtained from lesional skin of each patient (involved sample) and the other from non-lesional skin (uninvolved sample), taken at least 10 cm away from any active plaque. One biopsy was obtained from each healty control. Totally 180 samples were run on Affymetrix HU133 Plus 2.0 microarrays containing >54,000 gene probes. Experiment Overall Design: The raw data from 180 microarrays were processed using the Robust Multichip Average (RMA) method. The expression values in the table were after adjustment of RMA expression values (on the log scale) to account for batch and sex effects. Experiment Overall Design: Definition of abbreviations used in Sample records: NN = normal skin from controls; PN = uninvolved skin from cases; PP = involved skin from cases.
Project description:To determine whether murine GVHD associated tissue-specific signatures of donor CD8+ effector T cells are conserved at the same locations in humans developing GVHD, we compared the transcriptional profile of CD8+ T cells obtained simultaneously from the blood and skin of 5 patients developing acute pattern skin GVHD.
Project description:Sensitive skin is a hyperactive skin condtion, characterized by prickling, burning, itching, stinging, pain, or tingling sensation, which develops in response to various internal and external stimulants that can be tolerated by most people. The pathophysiology involved in the development of sensitive skin remains largely elusive. To characterize differential gene expression profiles in sensitive skin, we investigated the genome-wide patterns of gene expression from skin samples from subjects with sensitive or non-sensitive skin, following lactic acid challenge or normal saline application using cDNA microarrays. We recruited eighteen healthy volunteers with sensitive skin (n=9) or non-sensitive skin (n=9). From each subject, two skin samples were obtained following lactic acid or normal saline application.(18 samples/group) Based on the existence of sensitive skin and lactic acid challenge, samples were pooled into sets of three individuals each. Global transcriptome profiling was conducted using Affymetrix Human Genome U133 Plus 2.0 array.
Project description:Seborrheic keratosis is benign cutaneous neoplasm, the etiology of which is not well-known. To characterize differential gene expression profiles in seborrheic keratosis, we investigated the genome-wide patterns of gene expression from skin with seborrhic keratosis and uninvolved normal skin using cDNA microarrays. Comparative RNA expression profiles from non-lesional and lesional skin of 4 patients with seborrheic keratosis
Project description:the proteome of skin lesions from HHD patients was assembled and used for iTRAQ to analyze changes in skin lesions compared with unaffected individuals.