{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301106/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301106"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Integrating phenomics and transcriptomics to identify clinically meaningful endotypes of non-communicable inflammatory skin diseases","description":"Background: Precision medicine remains underutilized in the treatment of non-communicable inflammatory skin diseases (ncISD), largely due to the symptom-based clinical classifications, the intricate nature of relapsing-recurring inflammatory diseases and their significant heterogeneity, often involving clinically overlapping entities. Methods: We established a cohort of 390 patients with 22 ncISD. Integrating comprehensive clinical metadata with bulk skin transcriptome data (n = 727), we aimed to define clinically relevant endotypes independent of disease labels. A novel feature selection approach was applied to identify key gene signatures per endotype. Validation was performed in three independent, psoriasis gene expression datasets. Results: Thirteen molecular endotypes were characterized across ncISD that transcended conventional diagnostic categories. Prevalent diseases such as psoriasis and eczema distributed across multiple endotypes, underscoring their heterogeneity. An inferred ancestry tree clustered vendotypes based on distinct biological pathways. Six endotypes i were primarily associated with metabolic and skin structural processes, and seven with immune response pathways. Notably, endotype 12 showed significant enrichment for IL-23 signaling and corresponded to patients who (super)responded to anti-IL-23 therapy. Supervised feature selection enabled patient classification across all endotypes with 73% accuracy. External validation in independent psoriasis cohorts (n1 = 22, n2= 67, n3= 46) demonstrated consistent mapping to endotypes. Enrichment of anti-IL-23 responders in endotype 12 was observed in all cohorts confirming the generalizability of the endotype framework. Conclusion: Molecular endotyping is a robust strategy to stratify ncISD with the potential to replace subjective clinical classifications by mechanistically informed, objective diagnostics, which ultimately results in more precise and effective therapeutic decision-making.","dates":{"publication":"2026/09/30"},"accession":"GSE301106","cross_references":{"GSM":["GSM9075480","GSM9075481","GSM9075464","GSM9075486","GSM9075487","GSM9075465","GSM9075488","GSM9075466","GSM9075489","GSM9075467","GSM9075500","GSM9075482","GSM9075460","GSM9075461","GSM9075483","GSM9075462","GSM9075484","GSM9075485","GSM9075463","GSM9075479","GSM9075458","GSM9075459","GSM9075490","GSM9075491","GSM9075492","GSM9075470","GSM9075475","GSM9075497","GSM9075498","GSM9075476","GSM9075499","GSM9075477","GSM9075478","GSM9075493","GSM9075471","GSM9075472","GSM9075494","GSM9075495","GSM9075473","GSM9075496","GSM9075474","GSM9075501","GSM9075468","GSM9075469"],"GPL":["24676"],"GSE":["301106"],"taxon":["Homo sapiens"]}}