EGAGenomicsTobias Messemakerhttps://ega-archive.org/dacs/EGAC00001000788EGAEGA DAC EGAC00001000788EGAt.c.messemaker@vu.nlSystemic sclerosis is an autoimmune disease characterized by fibrosis of skin and multiple organs of which the pathogenesis is poorly understood. We studied differentially expressed coding and non-coding genes in relation to systemic sclerosis pathogenesis with a specific focus on antisense non-coding RNAs. Skin biopsy-derived RNAs from 14 early systemic sclerosis patients and six healthy individuals were sequenced with ion-torrent and analyzed using DEseq2. Overall, 4,901 genes with a fold change >1.5 and a false discovery rate <5% were detected in patients versus controls. Upregulated genes clustered in immunologic, cell adhesion, and keratin-related processes. Interestingly, 676 deregulated non-coding genes were detected, 257 of which were classified as antisense genes. Sense genes expressed opposite of these antisense genes were also deregulated in 42% of the observed sense-antisense gene pairs. The majority of the antisense genes had a similar effect sizes in an independent North American dataset with three genes (CTBP1-AS2, OTUD6B-AS1, and AGAP2-AS1) exceeding the study-wide Bonferroni-corrected P-value (PBonf < 0.0023, Pcombined = 1.1 × 10-9, 1.4 × 10-8, 1.7 × 10-6, respectively). In this study, we highlight that together with coding genes, (antisense) long non-coding RNAs are deregulated in skin tissue of systemic sclerosis patients suggesting a novel class of genes involved in pathogenesis of systemic sclerosis.Antisense Long Non-Coding RNAs Are Deregulated in Skin Tissue of Patients with Systemic Sclerosis.Messemaker Tobias C TC, Chadli Loubna L, Cai Guoshuai G, Goelela Varshna S VS, Boonstra Maaike M, Dorjée Annemarie L AL, Andersen Stefan N SN, Mikkers Harald M M HMM, van 't Hof Peter P, Mei Hailiang H, Distler Oliver O, Draisma Harmen H M HHM, Johnson Michael E ME, Orzechowski Nicole M NM, Simms Robert W RW, Toes Rene E M REM, Aarbiou Jamil J, Huizinga Tom W TW, Whitfield Michael L ML, DeGroot Jeroen J, de Vries-Bouwstra Jeska J, Kurreeman Fina Fdermis plus epidermis plus hypodermis, the integument, region of skin, Oct-11a, Systemic Sclerosis, pelt, Systemic, Otf-11, Skn-li, Sclerosis, skin zone, integumental organ, Client, epidermis, skin plus hypodermis, Oct11, skin region, BC033609, simple tissue, Skin-1a, Systemic sclerosis, tegument, Skin, integumentum commune, Skn-1a, skin benign neoplasm, skin, long, Tissue, vertebrate integument, dermoid system, entire skin, SKIN, Scleroderma, mKIAA0493, Epoc-1, Systemic Scleroderma., skin organ, portion of skin, vertebrate epidermis, integument, Patient, Clients, Fam91a1, Otf11, entire integument, AV220772, dermal system, skin and subcutaneous tissuefbwd4, dermis plus epidermis plus hypodermis, the integument, l(2)04454, DmelCG1772, region of skin, dac, Oct-11a, Systemic Sclerosis, pelt, CIB1, Systemic, Otf-11, Skn-li, Sclerosis, skin zone, p21[dacapo], integumental organ, dactylin, Client, epidermis, E130112M23Rik, cdi4, skin plus hypodermis, Oct11, skin region, dactylyn, p21, BC033609, CG1772, FBWD4, Cdi4, CDI4, p27, simple tissue, Skin-1a, Systemic sclerosis, Decapo, tegument, Skin, integumentum commune, Skn-1a, skin benign neoplasm, skin, shsf3, long, Tissue, shfm3, vertebrate integument, dermoid system, entire skin, E(Sev-CycE)2B, Fbw4, FBW4, SKIN, Scleroderma, mKIAA0493, Epoc-1, Systemic Scleroderma., Dach, CDKN2B, skin organ, portion of skin, SHFM3, vertebrate epidermis, Dac, DAC, p27[Dap], integument, Patient, dacapo/cyclin-dependent kinase interactor 4, Clients, AI182278, Fam91a1, Otf11, Dap, CES5A1, P15, fbw4, entire integument, SHSF3, AV220772, dermal system, skin and subcutaneous tissuethe integument, Materials, Systemic Sclerosis, pelt, ion, Systemic, Skn-li, F5I14.15, FON1, positive regulation by symbiont of host non-apoptotic programmed cell death, duba5, Keratin-Associated Proteins, 2600013N14Rik, FLORAL ORGAN NUMBER 1, F5I14_15, As2, SUB, D5H4S115, DmelCG12298, SUP, Keratin Associated, pathogenesis, SCRAMBLED, autoimmunity, cytopathology, CENTG1, BARS-50, Fs(3)Hor, Autoimmune, notch, KIF20A, Autoimmune condition, integumentum commune, DUBA5, ASYMMETRIC LEAVES 1, DmelCG2684, Autoimmune disease, stimulation by symbiont of host programmed cell death, Biopsies, ASYMMETRIC LEAVES 2, 50 kDa BFA-dependent ADP-ribosylation substrate, long, ASA, Bdr, Tissue, dermoid system, entire skin, ctbp1-A, Ax, NTef2, Super protein, Keratin Associated Proteins, sp, alpha-Keratin, SNAP-25, Adhesions, Centg1, TISP73, co, Adhesion, Fam91a1, Otf11, 50-kDaBFA-inducedADP-ribosylatedsubstrate, xctbp1, AV220772, skin and subcutaneous tissue, CtBP3|BARS, NECD, EG:140G11.1, l(1)N, swb, anatomical protrusion, wide/broad, Data Set, Chp, Co, Keratin, CtBP3, STRUBBELIG, integumental organ, CtBP1, Fs(3)Sz11, AU015433, ARABIDOPSIS PHANTASTICA-LIKE 1, Ionen, BC033609, shd, Diseases, modulation by symbiont of host system process, Cirrhosis, Genetic Materials, GENA70, simple tissue, mKIAA0167, fa, Genetic Material, cnt-g1, CtBP, histopathology, C-terminal-binding protein 3, INSDC_feature:gene, mKIAA0493, early, alpha Keratin, BARS, wide, vertebrate epidermis, Patient, clone 1.12, Material, spine, Horka, activation by symbiont of host programmed cell death, DUBA-5, CG2684, Fs(3)Horka, Cistron, entire integument, dermal system, n[fah], Bars, FLORAL DEFECTIVE 10, Cytokeratin, AT1G11140, dermis plus epidermis plus hypodermis, region of skin, GGAP2, Otf-11, Sclerosis, regulation by symbiont of host system process, Autoimmune Disease, EG:163A10.2, Gene, Coding, Pike, SUPERMAN, broad, autoimmune hypersensitivity disease, epidermis, CG12298, protrusion, induction by organism of non-apoptotic programmed cell death in other organism during symbiotic interaction, 1.1.1.-, hypersensitivity reaction type II disease, Fibroses, DmF2, single organism cell adhesion, PIKE, l(1)3Cb, Keratin Associated Protein, Medical, l(1)Ax, Skn-1a, lod, CtBP1-S, study, FOCUS, skin, Clinical, Genetic, CtBP1-L, Medical Coding, iones, cell adhesion molecule activity, mei-1794, DmelCG3936, clumped, causes, D5H4S115E, dNotch, ions, SKIN, Systemic Scleroderma., skin organ, Mif1, clustered, As-2, ATPHAN, ATMYB91, Clients, causality, SRF9, Associated Protein, AS-A, NICD, AW212749, CT13012, Systemic Scleroderma, Autoimmunity, 16-178, Autoimmune disorder, 16-55, Disease, MYB DOMAIN PROTEIN 91, Oct-11a, activation by organism of non-apoptotic programmed cell death in other organism, hemolysin activity, CtBP3/BARS, skin zone, anon-EST:Liang-1.12, Synaptosomal-associated 25 kDa protein, Cistrons, Client, Cell, F13M22.13, STRUBBELIG-RECEPTOR FAMILY 9, skin plus hypodermis, Oct11, skin region, Protein, spl, 1.1, Systemic sclerosis, Skin-1a, nd, tegument, Skin, skin benign neoplasm, MYB91, AGAP-2, Dub, vertebrate integument, Cell Adhesions, FLO10, F13M22_13, Lds, D4S115h, HERP, Scleroderma, Epoc-1, portion of skin, integument, Ion, SNAP, biopsy, CG3936, T19D16.8, SCMfalseDAC: Antisense long non-coding RNAs are deregulated in skin tissue of patients with systemic sclerosisData Access Committee EGAC000010007882025-1-9EGAC00001000788960629179949EGAS00001002751EGAD00001003832