Large-scale functional inference for skin-expressing lncRNAs using expression and sequence information.

Autor:	Patrick MT; Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA., Sreeskandarajan S; Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA.; Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA., Shefler A; Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA., Wasikowski R; Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA., Sarkar MK; Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA., Chen J; Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA.; College of Sciences, North Carolina State University, Raleigh, North Carolina, USA., Qin T; Department of Computational Medicine & Bioinformatics and., Billi AC; Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA., Kahlenberg JM; Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA.; Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA., Prens E; Department of Dermatology, Erasmus University Medical Center, Rotterdam, Netherlands., Hovnanian A; Laboratory of Genetic Skin Diseases, Imagine Institute, Paris, France., Weidinger S; Department of Dermatology and Allergy, University Medical Center Schleswig-Holstein, Kiel, Germany., Elder JT; Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA.; Ann Arbor Veterans Affairs Hospital, Ann Arbor, Michigan, USA., Kuo CC; Institute for Computational Genomics, Joint Research Center for Computational Biomedicine, RWTH Aachen University, Aachen, Germany., Gudjonsson JE; Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA., Tsoi LC; Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA.; Department of Computational Medicine & Bioinformatics and.; Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2023 Dec 22; Vol. 8 (24). Date of Electronic Publication: 2023 Dec 22.
DOI:	10.1172/jci.insight.172956
Abstrakt:	Long noncoding RNAs (lncRNAs) regulate the expression of protein-coding genes and have been shown to play important roles in inflammatory skin diseases. However, we still have limited understanding of the functional impact of lncRNAs in skin, partly due to their tissue specificity and lower expression levels compared with protein-coding genes. We compiled a comprehensive list of 18,517 lncRNAs from different sources and studied their expression profiles in 834 RNA-Seq samples from multiple inflammatory skin conditions and cytokine-stimulated keratinocytes. Applying a balanced random forest to predict involvement in biological functions, we achieved a median AUROC of 0.79 in 10-fold cross-validation, identifying significant DNA binding domains (DBDs) for 39 lncRNAs. G18244, a skin-expressing lncRNA predicted for IL-4/IL-13 signaling in keratinocytes, was highly correlated in expression with F13A1, a protein-coding gene involved in macrophage regulation, and we further identified a significant DBD in F13A1 for G18244. Reflecting clinical implications, AC090198.1 (predicted for IL-17 pathway) and AC005332.6 (predicted for IFN-γ pathway) had significant negative correlation with the SCORAD metric for atopic dermatitis. We also utilized single-cell RNA and spatial sequencing data to validate cell type specificity. Our research demonstrates lncRNAs have important immunological roles and can help prioritize their impact on inflammatory skin diseases.
Databáze:	MEDLINE
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