Non-invasive epidermal proteomics and machine learning permits molecular subclassification of psoriasis and eczematous dermatitis
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Abstract
Current approaches to selecting molecularly targeted therapies (biologics and oral small molecules) for immune-mediated skin diseases largely overlook interindividual immunologic heterogeneity, in part due to challenges of sample collection and the lack of broadly accepted biomarkers of therapeutic response. We sought to develop a rapid, minimally invasive method for obtaining and measuring biomarkers from skin and to generate predictive models of therapy response in two common inflammatory skin diseases, psoriasis and eczema. Here we present Detergent-based Immune Profiling System (DIPS), which enables painless and non-scarring collection of full thickness epidermal protein from skin and is suitable for downstream 45-plex immune protein biomarker analysis. We first developed machine learning models with the goal of accurately distinguishing between eczema (n=55) and psoriasis (n=74). Subsequently, models that correlate biomarker patterns with treatment response or nonresponse to commonly used biologic therapies were developed. We subsequently developed DIPS-Derm, a web-based platform that provides automated diagnostic and treatment predictions from data generated with DIPS. These results support the promise of artificial intelligence (AI)-driven precision dermatology and highlight the clinical potential of DIPS for personalized medicine in inflammatory skin disease.
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Skin was swabbed using a microfiber cosmetic applicator and approximately 40µL of surfactant. Swabbing was performed by rubbing the surfactant-coated applicator tip in a back-and-forth motion for 45 seconds, applying light pressure, over a 2mm-by-1mm rectangular area on lesional psoriasis or eczema skin.
What an interesting study, especially the findings relating to patient biomarkers and predicted therapeutic responsiveness.
A few questions arose for me: 1) for the swabbing procedure, how were the affected areas chosen? Were they on similar body parts/skin types? Did this differ for psoriatic or eczematic skin? This information in the Methods section could be informative for readers. 2) Did you test for intra-patient proteomic consistency by sampling more than once per patient? I'm interested in how intra- and inter-patient …
Skin was swabbed using a microfiber cosmetic applicator and approximately 40µL of surfactant. Swabbing was performed by rubbing the surfactant-coated applicator tip in a back-and-forth motion for 45 seconds, applying light pressure, over a 2mm-by-1mm rectangular area on lesional psoriasis or eczema skin.
What an interesting study, especially the findings relating to patient biomarkers and predicted therapeutic responsiveness.
A few questions arose for me: 1) for the swabbing procedure, how were the affected areas chosen? Were they on similar body parts/skin types? Did this differ for psoriatic or eczematic skin? This information in the Methods section could be informative for readers. 2) Did you test for intra-patient proteomic consistency by sampling more than once per patient? I'm interested in how intra- and inter-patient heterogeneity might differ from each other, affect clustering, or inform overall conclusions. 3) Similarly, could you compare to swabs/proteomics from non-affected skin areas from the same patients? 4) How do you think disease progression dynamics might also introduce noise in proteomics, i.e. could some of the differences in results be explained by sampling from different timepoints?
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