{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:54:02Z","timestamp":1793321642025,"version":"4.5.0"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Sebaceous glands drive acne, however, their role in other inflammatory skin diseases remains unclear. To shed light on their potential contribution to disease development, we investigated the spatial transcriptome of sebaceous glands in psoriasis and atopic dermatitis patients across lesional and non-lesional human skin samples. Both atopic dermatitis and psoriasis sebaceous glands expressed genes encoding key proteins for lipid metabolism and transport such as <jats:italic>ALOX15B, APOC1, FABP7, FADS1\/2, FASN, PPARG<\/jats:italic>, and <jats:italic>RARRES1.<\/jats:italic> Also, inflammation-related <jats:italic>SAA1<\/jats:italic> was identified as a common spatially variable gene. In atopic dermatitis, genes mainly related to lipid metabolism (e.g. <jats:italic>ACAD8, FADS6<\/jats:italic>, or <jats:italic>EBP)<\/jats:italic> as well as disease-specific genes, i.e., Th2 inflammation-related lipid-regulating <jats:italic>HSD3B1<\/jats:italic> were differentially expressed. On the contrary, in psoriasis, more inflammation-related spatially variable genes (e.g. <jats:italic>SERPINF1<\/jats:italic>, <jats:italic>FKBP5<\/jats:italic>, <jats:italic>IFIT1\/3, DDX58<\/jats:italic>) were identified. Other psoriasis-specific enriched pathways included lipid metabolism (e.g. <jats:italic>ACOT4, S1PR3)<\/jats:italic>, keratinization (e.g. <jats:italic>LCE5A, KRT5\/7\/16<\/jats:italic>), neutrophil degranulation, and antimicrobial peptides (e.g. <jats:italic>LTF, DEFB4A, S100A7-9<\/jats:italic>). In conclusion, our results show that sebaceous glands contribute to skin homeostasis with a cell type-specific lipid metabolism, which is influenced by the inflammatory microenvironment. These findings further support that sebaceous glands are not bystanders in inflammatory skin diseases, but can actively and differentially modulate inflammation in a disease-specific manner.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1334844","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T04:56:04Z","timestamp":1708059364000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":46,"title":["Spatial transcriptomics reveals altered lipid metabolism and inflammation-related gene expression of sebaceous glands in psoriasis and atopic dermatitis"],"prefix":"10.3389","volume":"15","author":[{"given":"Peter","family":"Seiringer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Hillig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Sch\u00e4bitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manja","family":"Jargosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Caroline","family":"Pilz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Eyerich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Szegedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Sochorov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Gruber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos C.","family":"Zouboulis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilo","family":"Biedermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Menden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kilian","family":"Eyerich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"T\u00f6r\u0151csik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4161\/derm.1.3.8473","article-title":"Sebum analysis of individuals with and without acne","volume":"1","author":"Pappas","year":"2009","journal-title":"Dermato-endocrinology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.12298","article-title":"Acne is an inflammatory disease and alterations of sebum composition initiate acne les(Mann 1947)ions","volume":"28","author":"Zouboulis","year":"2014","journal-title":"J Eur Acad Dermatol Venereology JEADV"},{"key":"B3","doi-asserted-by":"publisher","first-page":"15029","DOI":"10.1038\/nrdp.2015.29","article-title":"Acne vulgaris","volume":"1","author":"Moradi Tuchayi","year":"2015","journal-title":"Nat Rev Dis Primers"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.08.006","article-title":"Acne: transient arrest in the homeostatic host-microbiota dialog","volume":"40","author":"Szegedi","year":"2019","journal-title":"Trends Immunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s00109-005-0715-8","article-title":"Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands","volume":"84","author":"Alestas","year":"2006","journal-title":"J Mol Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-016-9389-5","article-title":"Beyond acne: Current aspects of sebaceous gland biology and function","volume":"17","author":"Zouboulis","year":"2016","journal-title":"Rev Endocrine Metab Disord"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.8.4512-4521.2005","article-title":"A toll-like receptor 2-responsive lipid effector pathway protects mammals against skin infections with gram-positive bacteria","volume":"73","author":"Georgel","year":"2005","journal-title":"Infection Immun"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0198323","article-title":"Genome wide analysis of TLR1\/2- and TLR4-activated SZ95 sebocytes reveals a complex immune-competence and identifies serum amyloid A as a marker for activated sebaceous glands","volume":"13","author":"Torocsik","year":"2018","journal-title":"PloS One"},{"key":"B9","doi-asserted-by":"publisher","first-page":"21510","DOI":"10.1038\/s41598-021-00907-1","article-title":"miR-146a modulates TLR1\/2 and 4 induced inflammation and links it with proliferation and lipid production via the indirect regulation of GNG7 in human SZ95 sebocytes","volume":"11","author":"Dull","year":"2021","journal-title":"Sci Rep"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2006.04.001","article-title":"Propionibacterium acnes and lipopolysaccharide induce the expression of antimicrobial peptides and proinflammatory cytokines\/chemokines in human sebocytes","volume":"8","author":"Nagy","year":"2006","journal-title":"Microbes Infect"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5701235","article-title":"Sebocytes express functional cathelicidin antimicrobial peptides and can act to kill propionibacterium acnes","volume":"128","author":"Lee","year":"2008","journal-title":"J Invest Dermatol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2009.384","article-title":"Sebum free fatty acids enhance the innate immune defense of human sebocytes by upregulating beta-defensin-2 expression","volume":"130","author":"Nakatsuji","year":"2010","journal-title":"J Invest Dermatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2015.11.013","article-title":"Expression of dermcidin in sebocytes supports a role for sebum in the constitutive innate defense of human skin","volume":"81","author":"Dahlhoff","year":"2016","journal-title":"J Dermatol Sci"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1029818","article-title":"Sebaceous immunobiology - skin homeostasis, pathophysiology, coordination of innate immunity and inflammatory response and disease associations","volume":"13","author":"Zouboulis","year":"2022","journal-title":"Front Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700844","article-title":"Isolation and expression of a Malassezia globosa lipase gene, LIP1","volume":"127","author":"DeAngelis","year":"2007","journal-title":"J Invest Dermatol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1111\/exd.14006","article-title":"Seborrheic dermatitis-Looking beyond Malassezia","volume":"28","author":"Wikramanayake","year":"2019","journal-title":"Exp Dermatol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2011.10662.x","article-title":"The fatty acid profile of the skin surface lipid layer in papulopustular rosacea","volume":"166","author":"Ni Raghallaigh","year":"2012","journal-title":"Br J Dermatol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.12.025","article-title":"Sebaceous gland-rich skin is characterized by TSLP expression and distinct immune surveillance which is disturbed in rosacea","volume":"137","author":"Dajnoki","year":"2017","journal-title":"J Invest Dermatol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1016\/j.it.2015.10.006","article-title":"The multi-modal immune pathogenesis of atopic eczema","volume":"36","author":"Eyerich","year":"2015","journal-title":"Trends Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/BF00408228","article-title":"Sebaceous glands in uninvolved skin of patients suffering from atopic dermatitis","volume":"270","author":"Wirth","year":"1981","journal-title":"Arch Dermatol Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.2007.02364.x","article-title":"Comparison of hydration, sebum and pH values in clinically normal skin of patients with atopic dermatitis and healthy controls","volume":"32","author":"Firooz","year":"2007","journal-title":"Clin Exp Dermatol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1001\/jamadermatol.2021.0734","article-title":"Long-term outcomes and prognosis in new-onset psoriasis","volume":"157","author":"Svedbom","year":"2021","journal-title":"JAMA Dermatol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1159\/000445942","article-title":"Marked reduction of the number and individual volume of sebaceous glands in psoriatic lesions","volume":"232","author":"Liakou","year":"2016","journal-title":"Dermatology"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.05.113","article-title":"Sebaceous gland atrophy in psoriasis: an explanation for psoriatic alopecia","volume":"136","author":"Ritti\u00e9","year":"2016","journal-title":"J Invest Dermatol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1080\/19381980.2017.1375636","article-title":"Sebaceous-immunobiology is orchestrated by sebum lipids","volume":"9","author":"Lovaszi","year":"2017","journal-title":"Dermato-endocrinology"},{"key":"B26","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/joim.13235","article-title":"So close, and yet so far away: The dichotomy of the specific immune response and inflammation in psoriasis and atopic dermatitis","volume":"290","author":"Sch\u00e4bitz","year":"2021","journal-title":"J Internal Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4636","article-title":"SpatialDE: identification of spatially variable genes","volume":"15","author":"Svensson","year":"2018","journal-title":"Nat Methods"},{"key":"B28","doi-asserted-by":"publisher","first-page":"9991175","DOI":"10.1155\/2021\/9991175","article-title":"The lncRNA H19\/miR-766-3p\/S1PR3 Axis Contributes to the Hyperproliferation of Keratinocytes and Skin Inflammation in Psoriasis via the AKT\/mTOR Pathway","volume":"2021","author":"He","year":"2021","journal-title":"Mediators Inflammation"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105238","article-title":"IL-17\/Th17 pathway is activated in acne lesions","volume":"9","author":"Kelhala","year":"2014","journal-title":"PloS One"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abo2787","article-title":"TREM2 macrophages induced by human lipids drive inflammation in acne lesions","volume":"7","author":"Do","year":"2022","journal-title":"Sci Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2003.12123.x","article-title":"Identification of the delta-6 desaturase of human sebaceous glands: expression and enzyme activity","volume":"120","author":"Ge","year":"2003","journal-title":"J Invest Dermatol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2011.10340.x","article-title":"Regulation of stearoyl-coenzyme A desaturase and fatty acid delta-6 desaturase-2 expression by linoleic acid and arachidonic acid in human sebocytes leads to enhancement of proinflammatory activity but does not affect lipogenesis","volume":"165","author":"Zouboulis","year":"2011","journal-title":"Br J Dermatol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/BF00406424","article-title":"Inhibitory effects of 13-cis-retinoic acid on human sebaceous glands","volume":"269","author":"Landthaler","year":"1980","journal-title":"Arch Dermatol Res"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.2001.3242","article-title":"Limited cooperation between peroxisome proliferator-activated receptors and retinoid X receptor agonists in sebocyte growth and development","volume":"74","author":"Kim","year":"2001","journal-title":"Mol Genet Metab"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2003.12411.x","article-title":"Expression of peroxisome proliferator-activated receptor and CCAAT\/enhancer binding protein transcription factors in cultured human sebocytes","volume":"121","author":"Chen","year":"2003","journal-title":"J Invest Dermatol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.mce.2015.08.001","article-title":"Insulin and insulin-like growth factor-1 can modulate the phosphoinositide-3-kinase\/Akt\/FoxO1 pathway in SZ95 sebocytes in vitro","volume":"415","author":"Mirdamadi","year":"2015","journal-title":"Mol Cell Endocrinol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700743","article-title":"Expression of lipogenic factors galectin-12, resistin, SREBP-1, and SCD in human sebaceous glands and cultured sebocytes","volume":"127","author":"Harrison","year":"2007","journal-title":"J Invest Dermatol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2006.07671.x","article-title":"Testosterone metabolism to 5alpha-dihydrotestosterone and synthesis of sebaceous lipids is regulated by the peroxisome proliferator-activated receptor ligand linoleic acid in human sebocytes","volume":"156","author":"Makrantonaki","year":"2007","journal-title":"Br J Dermatol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"3315","DOI":"10.3390\/nu15153315","article-title":"Linoleic acid induced changes in SZ95 sebocytes-comparison with palmitic acid and arachidonic acid","volume":"15","author":"Kovacs","year":"2023","journal-title":"Nutrients"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.01.042","article-title":"Single-cell transcriptome analysis of human skin identifies novel fibroblast subpopulation and enrichment of immune subsets in atopic dermatitis","volume":"145","author":"He","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2003.105","article-title":"Comparison of epidermal hydration and skin surface lipids in healthy individuals and in patients with atopic dermatitis","volume":"48","author":"Sator","year":"2003","journal-title":"J Am Acad Dermatol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-010-1076-x","article-title":"The usefulness of sebum check film for measuring the secretion of sebum","volume":"302","author":"Furuichi","year":"2010","journal-title":"Arch Dermatol Res"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1111\/all.15569","article-title":"Dysregulated lipidome of sebum in patients with atopic dermatitis","volume":"78","author":"Yin","year":"2023","journal-title":"Allergy"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2100749118","article-title":"Interleukins 4 and 13 drive lipid abnormalities in skin cells through regulation of sex steroid hormone synthesis","volume":"118","author":"Zhang","year":"2021","journal-title":"Proc Natl Acad Sci USA"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/exd.13867","article-title":"Transcriptomic and lipidomic profiling of eicosanoid\/docosanoid signalling in affected and non-affected skin of human atopic dermatitis patients","volume":"28","author":"Torocsik","year":"2019","journal-title":"Exp Dermatol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01906","article-title":"A novel function for 15-lipoxygenases in cholesterol homeostasis and CCL17 production in human macrophages","volume":"9","author":"Snodgrass","year":"2018","journal-title":"Front Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2001.113237","article-title":"Thymus and activation-regulated chemokine in atopic dermatitis: Serum thymus and activation-regulated chemokine level is closely related with disease activity","volume":"107","author":"Kakinuma","year":"2001","journal-title":"J Allergy Clin Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33869","article-title":"Neutrophil gelatinase-associated lipocalin mediates 13-cis retinoic acid-induced apoptosis of human sebaceous gland cells","volume":"118","author":"Nelson","year":"2008","journal-title":"J Clin Invest"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.18562","article-title":"Isotretinoin is indirectly effective in sebocytes","volume":"182","author":"Kovacs","year":"2020","journal-title":"Br J Dermatol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/jid.1955.106","article-title":"Histology and cytochemistry of human skin. VIII. Mitochondria in the sebaceous glands","volume":"25","author":"Montagna","year":"1955","journal-title":"J Invest Dermatol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.5021\/ad.2021.33.5.425","article-title":"Azidothymidine downregulates insulin-like growth factor-1 induced lipogenesis by suppressing mitochondrial biogenesis and mitophagy in immortalized human sebocytes","volume":"33","author":"Yoo","year":"2021","journal-title":"Ann Dermatol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/s41419-022-05045-8","article-title":"SerpinB7 deficiency contributes to development of psoriasis via calcium-mediated keratinocyte differentiation dysfunction","volume":"13","author":"Zheng","year":"2022","journal-title":"Cell Death Dis"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1816847116","article-title":"Epigenetic upregulation of FKBP5 by aging and stress contributes to NF-kappaB-driven inflammation and cardiovascular risk","volume":"116","author":"Zannas","year":"2019","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B54","doi-asserted-by":"publisher","first-page":"e12464","DOI":"10.1111\/appy.12464","article-title":"Association of FKBP5 gene variants with depression susceptibility: A comprehensive meta-analysis","volume":"13","author":"Fan","year":"2021","journal-title":"Asia Pac Psychiatry"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jpsychires.2021.08.014","article-title":"Regulatory functions of FKBP5 intronic regions associated with psychiatric disorders","volume":"143","author":"Mendon\u00e7a","year":"2021","journal-title":"J Psychiatr Res"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00579","article-title":"Systemic inflammation and cardiovascular comorbidity in psoriasis patients: causes and consequences","volume":"9","author":"Boehncke","year":"2018","journal-title":"Front Immunol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.2340\/actadv.v101.565","article-title":"Common fundamentals of psoriasis and depression","volume":"101","author":"Holsken","year":"2021","journal-title":"Acta Derm Venereol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"7729","DOI":"10.1038\/s41467-022-35319-w","article-title":"Spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases","volume":"13","author":"Sch\u00e4bitz","year":"2022","journal-title":"Nat Commun"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13059-017-1382-0","article-title":"SCANPY: large-scale single-cell gene expression data analysis","volume":"19","author":"Wolf","year":"2018","journal-title":"Genome Biol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"2122","DOI":"10.12688\/f1000research.9501.2","article-title":"\"A step-by-step workflow for low-level analysis of single-cell RNA-seq data with Bioconductor.\"","volume":"5","author":"Lun","year":"2016","journal-title":"F1000Research"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0113-3","article-title":"\"Efficient integration of heterogeneous single-cell transcriptomes using Scanorama.\"","volume":"37","author":"Hie","year":"2019","journal-title":"Nat Biotechnol"},{"key":"B62","article-title":"Umap: Uniform manifold approximation and projection for dimension reduction","author":"McInnes","year":"2018","journal-title":"arXiv preprint"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa1009","article-title":"glmGamPoi: fitting Gamma-Poisson generalized linear models on single cell count data","volume":"36","author":"Ahlmann-Eltze","year":"2021","journal-title":"Bioinformatics"},{"key":"B64","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Society: Ser B (Methodological)"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1039\/C5MB00663E","article-title":"ReactomePA: an R\/Bioconductor package for reactome pathway analysis and visualization","volume":"12","author":"Yu","year":"2016","journal-title":"Mol Biosyst"},{"key":"B66","volume-title":"org.Hs.eg.db: Genome Wide Annotation for Human. R package version 3.13.0","author":"Carlson","year":"2021"},{"key":"B67","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1214\/aoms\/1177730491","article-title":"On a test of whether one of two random variables is stochastically larger than the other","volume":"18","author":"Mann","year":"1947","journal-title":"Ann Math Stat"},{"key":"B68","article-title":"trevismd\/statannotations: v0.5","author":"Charlier","year":"2022","journal-title":"Zenodo"},{"key":"B69","first-page":"3","volume-title":"Teoria statistica delle classi e calcolo delle probabilita","author":"Bonferroni","year":"1936"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1334844\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T04:56:11Z","timestamp":1708059371000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1334844\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,16]]},"references-count":69,"alternative-id":["10.3389\/fimmu.2024.1334844"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1334844","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,16]]},"article-number":"1334844"}}