PAXDBapplication/xmlhttp://pax-db.org/downloads/latest/datasets/bioprojects-abundance-files-v4.0.zipprimaryOK2000000ProteomicsChristian von Mering10090https://pax-db.org/dataset/10090/753102295mering@imls.uzh.chUniversity of ZurichPAXDBFor the rescaling, the datasets are first parsed or processed such that the data reflect proportional abundances of whole protein molecules (i.e. proportionality to counts of complete, individual protein molecules, not to molecular weights, protein volumes, or digested peptides). In the case of spectral counting data protein. The proportional abundances are rescaled linearly to add up to one million; this means the abundance of each protein of interest is finally expressed in (parts per million,) relative to all other proteins in a sample. For a given protein abundance dataset, we then compute the absolute log abundance ratios of all pairs of proteins annotated to be functionally linked. The median of these absolute log abundance ratios represents an indirect quality metric: the closer it is to zero, the better (i.e. the more there is consistency between abundance values and functional annotations such as protein complexes or pathways). We then compute a background expectation for this metric, by permuting the abundance values in a given dataset randomly, and recomputing the median log abundance ratios. The permutation is repeated several times, yielding a distribution of medians. The actually observed median is then expressed as a Z-score distance to the random distribution ofmedians—this distance is termed the interaction consistency score.Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)-a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin, we targeted TGF-β activity with losartan in a preclinical setting. Long-term treatment of RDEB mice efficiently reduced TGF-β signaling in chronically injured forepaws and halted fibrosis and subsequent fusion of the digits. In addition, proteomics analysis of losartan- vs. vehicle-treated RDEB skin uncovered changes in multiple proteins related to tissue inflammation. In line with this, losartan reduced inflammation and diminished TNF-α and IL-6 expression in injured forepaws. Collectively, the data argue that RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF-β-mediated inflammation, and matrix remodeling. Inhibition of TGF-β activity limits these unwanted outcomes and thereby substantially ameliorates long-term symptoms.Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms.Nyström Alexander A, Thriene Kerstin K, Mittapalli Venugopal V, Kern Johannes S JS, Kiritsi Dimitra D, Dengjel Jörn J, Bruckner-Tuderman Leena LAdd, DmelCG43443, ADD, ADD-87, Hts-RC, data, AU023367, Data Set, protein complex, supply, Proteins, Ovhts, Gene, HtsRC, CG9325, protein, neutral molecular compounds, protein-containing complex, Dmel_CG9325, Xt, Peptide, 1B1, add, Polypeptides, anon-EST:Posey9, protein polypeptide chains, native protein, peptido, htsRC, GLI3-190, natural protein, polypeptide chain, Add-hts, Protein, CG43443, Gene Products, l(2)k14523, Dmel_CG34197, l(2)00634, median, Ovhts-RC, background, supply and distribution, protein aggregate, all_pairs, molecule, Bph, molecula, Random selection by shearing, oligonucleotide random primer, proportion, HTS-R1, HTS, Hts, molecules, peptides, l(2)k06121, adducin, GLI3FL, distribution, AI854843, proportionality, add-like, HTS-RC, rate, proteins, Molekuel, Pdn, sample population, introduction, Protein Gene Products, Gene Proteins, Adducin, RANDOM, 10^[-6], ppm, sample, supply., quotient, Peptid, peptidos, Polypeptide, Attention Deficit Hyperactivity Disorder, l(2)01103, EST D, CG34197, HtsF, ratioMK 954, other disease, Autosomal Recessive, 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole, Dystrophic Epidermolysis Bullosa, Cockayne-Touraine Type Epidermolysis Bullosa, Cockayne Touraine Disease, Dystrophic, Epidermolysis Bullosa Dystrophica, Recessive, Cozaar, disorders, Losartan Monopotassium, Hallopeau-Siemens Type, Epidermolysis Bullosas, losartan, 2-Butyl-4-chloro-1-((2'-(1H-etrazol-5-yl) (1, 1'-biphenyl)-4-yl)methyl)-1H-imidazole-5-methanol, epidermolysis bullosa, Cockayne Touraine Type Epidermolysis Bullosa, diseases, Diseases, Hallopeau Siemens Disease, disease or disorder, condition, Dystrophic Epidermolysis, diseases and disorders, Cockayne-Touraine Type, Dystrophic Epidermolysis Bullosas, (2-butyl-4-chloro-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazol-5-yl)methanol, Epidermolysis Bullosa Dystrophicas, Hallopeau-Siemens Disease, human disease, DuP-753, Bullosa, Salt, Monopotassium Salt, Bullosa Dystrophica, Losartan, MK954, Dystrophica, Dominant, dermolytic, DEB, non-neoplastic, disease, Losartan Monopotassium Salt, Hallopeau Siemens Type, Cockayne Touraine Type, DuP753, Cockayne-Touraine Disease, Epidermolysis bullosa dystrophica, DuP 753, Bullosas, MK-954, disorder, Epidermolysis, Homo sapiens disease, medical condition., Dermolytic epidermolysis bullosa, Losartan Potassium, Dystrophicas, Potassium, Epidermolysis Bullosa, Bullosa Dystrophicasskin benign neoplasm, dermis plus epidermis plus hypodermis, the integument, region of skin, Oct-11a, skin, pelt, Otf-11, Skn-li, vertebrate integument, dermoid system, entire skin, skin zone, muscle, integumental organ, Skn-1a., SKIN, muscle element, mKIAA0493, Epoc-1, epidermis, skin organ, portion of skin, skin plus hypodermis, vertebrate epidermis, Oct11, skin region, integument, musculus, BC033609, Fam91a1, Otf11, Skin-1a, entire integument, tegument, AV220772, Skin, dermal system, skin and subcutaneous tissue, integumentum communeDifferentiation-Inducing Protein, Myeloid Differentiation-Inducing Protein, the integument, B-Cell Stimulatory Factor-2, CDF, 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole, Collagens, Inflammations, short stature, Activity, pelt, determination, Laboratory, Myeloid, SOFT, Skn-li, Il-6, Mus domesticus, Hepatocyte-Stimulating Factor, Losartan Monopotassium, CASP-14, Progress Reports, losartan, House Mouse, soft, MAGE-E1 antigen, ter, B-cell stimulatory factor 2, 1'-biphenyl)-4-yl)methyl)-1H-imidazole-5-methanol, B Cell, B Cell Stimulatory Factor 2, diseases, Summary Report, IL-6, symptoms, Interferon beta-2, pathogenesis, Hybridoma growth factor, diseases and disorders, pale/ple, Zyderm, xtnf-alpha, Summary Reports, integumentum commune, treatment, portion of tissue, human disease, inflammatory response, Progress Report, regg1, CG12919, Microfibril Collagen Hemostat, Tissue, Salt, dermoid system, hypoplasia, entire skin, Swiss Mice, proteins, MK954, genetic, DIF, B Cell Differentiation Factor 2, Progress, interleukin-6 receptor ligand, Field Reports, collagen, DuP753, HCA1, Bsg75C, Collagen Fleece, signaling process, Fam91a1, Otf11, disease management, Therapies, TNFSF2, DuP 753, onychodysplasia, MK-954, Homo sapiens disease, TH, Collagen, AV220772, skin and subcutaneous tissue, Losartan Potassium, FACE, single organism signaling, dif, Therapy, screening, MK 954, tnfa, Cozaar, familial, mouse, TNFA, DmelCG10118, Th, B Cell Stimulatory Factor-2, beta-2, integumental organ, HSF, BSF2, severe generalised RDEB, Interferon beta 2, Investigative Report, Term, Regg1, BC033609, Mini-ICE, DAMAGE, Hepatocellular carcinoma-associated protein 1, tnf-alpha, tissue portion, Cirrhosis, simple tissue, Skin fragility, PIX2, Differentiation Factor-2, Mus musculus, Differentiation Factor 2, Caspase-14 subunit p10, mice, Field, Swiss Mouse, signs, Losartan, Caspase-14 subunit p19, TNFalpha, BcDNA:RH51659, MICE, severe generalised recessive dystrophic epidermolysis bullosa, Plasmacytoma, Treatments, mKIAA0493, domesticus, disease, IFNB2, Report, vertebrate epidermis, FAE, Plasmacytoma Growth Factor, facial dysmorphism, Collagen Felt, Tnfa, inherited genetic, Mouse, entire integument, dermal system, Innate, Interferon, mMage-e1, dermis plus epidermis plus hypodermis, 3.4.22.-, other disease, Inflammatory Response, biological signaling, TNF-alpha, region of skin, Peptidomics, Otf-11, TNF, B-cell hybridoma growth factor, alpha-Collagen, Gene, B-Cell, mini-ICE, B-Cell Differentiation Factor, epidermis, and hypotrichosis, TNF-a, HGF, Microfibril, Investigative, reduced, House, Dermodress, Collastat, Hepatocyte Stimulating Factor, Gene Products, disease or disorder, Mus musculus domesticus, Fibroses, Growth Factor, tiny, CTL differentiation factor, Mice, Skn-1a, severe generalized recessive dystrophic epidermolysis bullosa, (2-butyl-4-chloro-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazol-5-yl)methanol, skin, Differentiation Factor, findings., DuP-753, Swiss, Hybridoma Growth Factor, RATTNF, complementation group E, Interleukin 6, Avitene, inflammation, causes, AI847422, SKIN, DmelCG12919, Ect1, alpha Collagen, non-neoplastic, skin organ, Losartan Monopotassium Salt, DmelCG4216, darth, Innate Inflammatory Response, Pale, causality, disorder, IL6, dTH1, Investigative Reports, constitutitional genetic, Collagenfleece, Potassium, DH65B, small, Fanconi anemia, data, visage, CG10118, findings, Oct-11a, MGI-2, facia/facies, xtnf, Proteins, Alpha-dystrobrevin-associated MAGE Protein, disorders, ggr, skin zone, medical condition, Myeloid Differentiation Inducing Protein, 2-Butyl-4-chloro-1-((2'-(1H-etrazol-5-yl) (1, Faces, dt1, tnfsf2, skin plus hypodermis, Oct11, skin region, native protein, Mus, IFN-beta-2, Research Reports, chemical analysis, Protein, LCE, Collagen Hemostat, condition, BSF-2, Skin-1a, DTH, WDR51A, tegument, Skin, Pangen, skin benign neoplasm, B-Cell Differentiation Factor-2, IFN-beta 2, Ple, underdeveloped, RGD1560259, other collagen, vertebrate integument, CG4216, Interleukin HP-1, Avicon, Monopotassium Salt, House Mice, Fragile skin, signalling, Epoc-1, Laboratory Mice, Protein Gene Products, Gene Proteins, portion of skin, B Cell Differentiation Factor, signalling process, Hybridoma, Therapeutic, Reports, integument, Innate Inflammatory Responses, dTH65B, B-Cell Stimulatory Factor 2, Egr, severe generalized RDEB, Treatment, assay, VII, Summary, hereditary, General activity, Laboratory Mouse, Severe, Tnfsf1a, Field Report0falseM.musculus - Skin, SC (Nystroemetal.,embomolmed,2015)abundance based on Spectral counting, Interaction consistency score: 8.5, Coverage: 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