Machine learning driven biomarker discovery for the discrimination between allergic and irritant contact dermatitis
Ontology highlight
ABSTRACT: Allergic and irritant contact dermatitis induces different immunological cascades, involving a plethora of immune cells as well as keratinocytes. 96 patients were investigated using mRNA microarray experiments, of which 88 passed our QC criteria. Patients were topically exposed to allergens (nickel (Ni), epoxy resin (EP) and methylchloroisothiazolinone (CM)), irritants (sodium lauryl sulfate (SL) and nonanoic acid (NO)) for 48 hours or were left untreated.
Project description:Allergic and irritant contact dermatitis induces different immunological cascades, involving a plethora of immune cells as well as keratinocytes. This highly interwoven network is regulated by miRNAs. However, which miRNAs are involved during allergic- and irritant-induced contact dermatitis is not well investigated. Therefore, we analyzed miRNA and mRNA expression data of the same sample from positive patch test reactions from 27 patients topically exposed to allergens (nickel (Ni), epoxy resin (EP) and methylchloroisothiazolinone (CM); each n=5), irritants (sodium lauryl sulfate (SL, n=9) and nonanoic acid (NO, n=5)), as well as healthy skin (n=5). This is the mRNA dataset for these experiments.
Project description:We aimed to characterize transcriptomic changes over time (baseline, 2 hours, 48 hours and 96 hours) after nickel-induced contact dermatitis in 6 human probands. As a contrast, 7 patients with SLS-induced irritant contact dermatitis were included. Therefore, the patch tests were applied onto the back of the individuals and punch biopsies were taken at the respective time points. Only skin with clear reactions was further used for transcriptomic analysis. Using gene set enrichment analysis and leukocyte deconvolution algorithm, we were able to identify important immune cell subsets and related functions within the human skin.
Project description:Allergic and irritant contact dermatitis induces different immunological cascades, involving a plethora of immune cells as well as keratinocytes. This highly interwoven network is regulated by miRNAs. However, which miRNAs are involved during allergic- and irritant-induced contact dermatitis is not well investigated. Therefore, we analyzed miRNA and mRNA expression data of the same sample from positive patch test reactions from 27 patients topically exposed to allergens (nickel (Ni), epoxy resin (EP) and methylchloroisothiazolinone (CM); each n=5), irritants (sodium lauryl sulfate (SL, n=9) and nonanoic acid (NO, n=5)), as well as healthy skin (n=5).
Project description:Genes involved in the inflammatory response resulting in allergic contact dermatitis (ACD) are only partly known. In this study, we introduce the use of high density oligonucleotide arrays for gene expression profiling in human skin during the elicitation of ACD. Skin biopsies from normal and nickel-exposed skin were obtained from 7 nickel-allergic patients and 5 non-allergic controls at four different time points during elicitation of eczema: 0h, 7h, 48h and 96h. Each gene expression profile was analysed by hybridization to high density oligonucletide arrays. Cluster analysis of 74 genes found to be differentially expressed in the patients over time revealed that the patient samples may be categorised into two groups: An early time point group (0h and 7h) and a late time point group (48h and 96h). Compared to the early time points, late time point skin samples were characterised by the up-regulation of inflammatory molecules including genes involved in the class I antigen presenting pathway and genes involved in lymphocyte adhesion and motility ; Correspondence analysis including both patients and controls revealed three distinct groups: i) the control group, ii) the early time point patient group (0h and 7h) and iii) the late time point patient group (48h and 96h). Experiment Overall Design: For the microarray study, 7 nickel-allergic patients and 5 non-allergic controls were recruited. All subjects were female. The skin covering the upper nates was exposed to nickel delivered during a patch test. Skin biopsies were taken to generate a time-series. Skin was exposed to nickel for 0h, 7h, 48h and 96h. Experiment Overall Design: All nickel allergic patients reacted with visible eczama at the 48h and 96h time-points. No eczema was vissible at the 0h or 7h time-points. Control subjects did not show visible eczema at any time-point. Experiment Overall Design: RNA was extracted from the skin biopsies and 34 biopsies yielded RNA of sufficient quantity and quality for micro-array analysis.
Project description:Donor-matched human skin biopsies were taken from non-lesional (NL) and lesional skin of positive patch-test reactions to nickel at 24h, 48h, and 120h post allergen application, respectively, and bulk RNA-seq was performed.
Project description:Atopic dermatitis is a multifactorial allergic skin disease in humans and dogs. Genetic predisposition, immunologic hyperreactivity, a defective skin barrier and environmental factors play a role in its pathogenesis. The aim of this study was to analyze gene expression in the skin of dogs sensitized to house dust mite antigens. Skin biopsies were collected from six sensitized and six non-sensitized Beagle dogs from normal, non-treated skin before and six and 24 hours after challenge using skin patches with allergen or saline as a negative control. Transcriptome analysis was performed by the use of DNA microarrays and expression of selected genes was validated by quantitative real-time RT-PCR. Expression data was compared between groups (unpaired design). After 24 hours 597 differentially expressed genes were detected, 361 with higher and 226 with lower mRNA concentration in allergen treated skin of sensitized dogs compared to their saline-treated skin and compared to the control specimens. Functional annotation clustering, pathway-and co-citation analysis showed, that the genes with increased expression were involved in inflammation, wound healing and immune response. In contrast, genes with decreased expression in sensitized dogs were associated with differentiation and barrier function of the skin. As the sensitized dogs did not show differences in the untreated skin compared to controls, inflammation after allergen patch test probably led to a decrease in the expression of genes important for barrier formation. Our results further confirm the similar pathophysiology of human and canine atopic dermatitis and revealed genes previously not known to be involved in canine atopic dermatitis. 60 canine (dog) skin tissue samples; six sensitized and six non-sensitized Beagle dogs; samples collected before (0h), 6h and 24h after challenge with allergen; samples collected from a skin area treated with saline and from an area treated with allergen
Project description:Background: Psoriasis is a chronic disease characterized by the development of scaly red skin lesions and possible co-morbid conditions. The psoriasis lesional skin transcriptome has been extensively investigated, but mRNA levels do not necessarily reflect protein abundance. Methods: Lesional (PP) and uninvolved (PN) skin samples from 14 patients were analyzed using high-throughput complementary DNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: We identified 4122 differentially expressed genes (DEGs) along with 748 differentially expressed proteins (DEPs). Global shifts in mRNA were modestly correlated with changes in protein abundance (r = 0.40). We identified similar numbers of increased and decreased DEGs, but 4-fold more increased than decreased DEPs. Ribosomal subunit and translation proteins were elevated within lesions, without a corresponding shift in mRNA expression (RPL3, RPS8, RPL11). We identified 209 differentially expressed genes/proteins (DEGPs) with corresponding trends at the transcriptome and proteomic levels. Most DEGPs were similarly altered in at least one other skin disease. Psoriasis-specific and non-specific DEGPs had distinct cytokine-response patterns, with only the former showing disproportionate induction by IL-17A in cultured keratinocytes. Conclusions: Our findings reveal global imbalance between the number of increased and decreased proteins in psoriasis lesions, consistent with heightened translation. This effect could not have been discerned from mRNA profiling data alone. We have also identified high-confidence DEGPs and shown that only those most specific to psoriasis are enriched with IL-17A targets. RNA-seq-based comparison between gene expression in psoriasis lesions and uninvolved skin from 14 patients
Project description:mRNA array analysis was carried out using total RNA of skin biopsies from lesional and non-lesional skin of three atopic dermatitits patients and four healthy individuals.
Project description:RNA expression profiling was carried out for systemic sclerosis (scleroderma) on skin biopsies obtained from both diffuse scleroderma (dcSSc) and limited scleroderma (lcSSc) subjects patients and compared to normal subjects. The patient group comprised of 4 dcSSc and 2 lcSSc subjects, all of whom were Caucasian and belonged to the age range of 42-73 (Mean age = 61.6). Patient sample set consisted of 3 females and 3 males. Race matched female volunteers from the same geographical area were recruited as controls (n = 4) and belonged to the age range of 41-62 (Mean age = 52).
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.