{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:28:21Z","timestamp":1790627301051,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T00:00:00Z","timestamp":1612310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013276","name":"Interreg","doi-asserted-by":"publisher","award":["Interreg Italia-Slovenia, ISE-EMH 07\/2019"],"award-info":[{"award-number":["Interreg Italia-Slovenia, ISE-EMH 07\/2019"]}],"id":[{"id":"10.13039\/100013276","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The high volume of information produced in the age of omics was and still is an important step to understanding several pathological processes, providing the enlightenment of complex molecular networks and the identification of molecular targets associated with many diseases. Despite these remarkable scientific advances, the majority of the results are disconnected and divergent, making their use limited. Skin diseases with alterations in the Notch signaling pathway were extensively studied during the omics era. In the GWAS Catalog, considering only studies on genomics association (GWAS), several works were deposited, some of which with divergent results. In addition, there are thousands of scientific articles available about these skin diseases. In our study, we focused our attention on skin diseases characterized by the impairment of Notch signaling, this pathway being of pivotal importance in the context of epithelial disorders. We considered the pathologies of five human skin diseases, Hidradenitis Suppurativa, Dowling Degos Disease, Adams\u2013Oliver Syndrome, Psoriasis, and Atopic Dermatitis, in which the molecular alterations in the Notch signaling pathway have been reported. To this end, we started developing a new multiomics platform, PlatOMICs, to integrate and re-analyze omics information, searching for the molecular interactions involved in the pathogenesis of skin diseases with alterations in the Notch signaling pathway.<\/jats:p>","DOI":"10.3390\/ijms22041523","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T20:31:51Z","timestamp":1612384311000},"page":"1523","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Multiomics Integration in Skin Diseases with Alterations in Notch Signaling Pathway: PlatOMICs Phase 1 Deployment"],"prefix":"10.3390","volume":"22","author":[{"given":"Lucas Andr\u00e9 Cavalcanti","family":"Brand\u00e3o","sequence":"first","affiliation":[{"name":"Department of Advanced Diagnostics, Institute for Maternal and Child Health IRCCS Burlo Garofolo, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1954-4126","authenticated-orcid":false,"given":"Paola Maura","family":"Tricarico","sequence":"additional","affiliation":[{"name":"Department of Advanced Diagnostics, Institute for Maternal and Child Health IRCCS Burlo Garofolo, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7592-2443","authenticated-orcid":false,"given":"Rossella","family":"Gratton","sequence":"additional","affiliation":[{"name":"Department of Advanced Diagnostics, Institute for Maternal and Child Health IRCCS Burlo Garofolo, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almerinda","family":"Agrelli","sequence":"additional","affiliation":[{"name":"Department of Pathology, Federal University of Pernambuco (UFPE), Recife 1235, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5886-9129","authenticated-orcid":false,"given":"Luisa","family":"Zupin","sequence":"additional","affiliation":[{"name":"Department of Advanced Diagnostics, Institute for Maternal and Child Health IRCCS Burlo Garofolo, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3460-1413","authenticated-orcid":false,"given":"Haissam","family":"Abou-Saleh","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences, College of Arts and Sciences, University of Qatar, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Moura","sequence":"additional","affiliation":[{"name":"Department of Advanced Diagnostics, Institute for Maternal and Child Health IRCCS Burlo Garofolo, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8493-1168","authenticated-orcid":false,"given":"Sergio","family":"Crovella","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences, College of Arts and Sciences, University of Qatar, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-642-19683-6_1","article-title":"Sensing the Environment: Regulation of Local and Global Homeostasis by the Skin\u2019s Neuroendocrine System","volume":"212","author":"Slominski","year":"2012","journal-title":"Adv. Anat. Embryol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s00005-017-0477-3","article-title":"Skin Immunity","volume":"66","author":"Matejuk","year":"2018","journal-title":"Arch. Immunol. Exp."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"108537","DOI":"10.1016\/j.clim.2020.108537","article-title":"The cutaneous and intestinal microbiome in psoriatic disease","volume":"218","author":"Le","year":"2020","journal-title":"Clin. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1111\/exd.14158","article-title":"Dialog between skin and its microbiota: Emergence of \u201cCutaneous Bacterial Endocrinology","volume":"29","author":"Racine","year":"2020","journal-title":"Exp. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/nature05662","article-title":"Mechanisms of sensory transduction in the skin","volume":"445","author":"Lumpkin","year":"2007","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2018.02727","article-title":"Leveraging multilayered \u201comics\u201d data for atopic dermatitis: A road map to precision medicine","volume":"9","author":"Ghosh","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Olbrich, M., K\u00fcnstner, A., Witte, M., Busch, H., and F\u00e4hnrich, A. (2019). Genetics and Omics Analysis of Autoimmune Skin Blistering Diseases. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02327"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/978-1-4614-0899-4_10","article-title":"Notch Signaling and the Developing Skin Epidermis","volume":"Volume 727","author":"Reichrath","year":"2012","journal-title":"Notch Signaling in Embryology and Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1152\/physrev.00005.2017","article-title":"Notch Signaling in Development, Tissue Homeostasis, and Disease","volume":"97","author":"Siebel","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Gratton, R., Tricarico, P.M., Moltrasio, C., Lima Estev\u00e3o de Oliveira, A.S., Brand\u00e3o, L., Marzano, A.V., Zupin, L., and Crovella, S. (2020). Pleiotropic Role of Notch Signaling in Human Skin Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124214"},{"key":"ref_11","unstructured":"(2020, November 18). Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=%28Hidradenitis+Suppurativa+OR+Dowling+Degos+Disease+OR+Adams-Oliver+Syndrome+OR+Psoriasis+OR+Atopic+Dermatitis%29+AND+%28genome+OR+transcriptome+OR+proteome+OR+microbiome%29&filter=pubt.classicalarticle&filter=pubt.clinicalstudy&filter=pubt.clinicaltrial&filter=pubt.comment&filter=pubt.dataset&filter=pubt.journalarticle&filter=pubt.letter&filter=pubt.observationalstudy&filter=pubt.technicalreport&filter=years.2016-2020."},{"key":"ref_12","unstructured":"(2020, November 17). Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=%28+Hidradenitis+Suppurativa+OR+Dowling+Degos+Disease+OR+Adams%E2%80%93Oliver+Syndrome+OR+Psoriasis+OR+Atopic+Dermatitis%29+AND+%28%22multi+omics%22+or+%22multi-omics%22+or+%22multiomics%22%29&filter=pubt.classicalarticle&filter=pubt.clinicalstudy&filter=pubt.clinicaltrial&filter=pubt.comment&filter=pubt.dataset&filter=pubt.journalarticle&filter=pubt.letter&filter=pubt.observationalstudy&filter=pubt.technicalreport."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"108470","DOI":"10.1016\/j.clim.2020.108470","article-title":"Not your average joint: Towards precision medicine in psoriatic arthritis","volume":"217","author":"Castillo","year":"2020","journal-title":"Clin. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s11302-019-09676-z","article-title":"Role of purines in regulation of metabolic reprogramming","volume":"15","author":"Tang","year":"2019","journal-title":"Purinergic Signal."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1159\/000500402","article-title":"Genetics of Atopic Dermatitis: From DNA Sequence to Clinical Relevance","volume":"235","author":"Brown","year":"2019","journal-title":"Dermatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e16527","DOI":"10.1097\/MD.0000000000016527","article-title":"Association of atopic dermatitis with obesity via a multi-omics approach: A protocol for a case\u2013control study","volume":"98","author":"Son","year":"2019","journal-title":"Medicine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.jid.2016.10.034","article-title":"As in Atopic Dermatitis, Nonlesional Skin in Allergic Contact Dermatitis Displays Abnormalities in Barrier Function and Ceramide Content","volume":"137","author":"Kim","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"eaav2685","DOI":"10.1126\/scitranslmed.aav2685","article-title":"The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype","volume":"11","author":"Leung","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Jhamb, D., Shu, L., Arneson, D., Rajpal, D.K., and Yang, X. (2019). Multi-omics integration reveals molecular networks and regulators of psoriasis. Bmc Syst. Biol., 13.","DOI":"10.1186\/s12918-018-0671-x"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"102349","DOI":"10.1016\/j.jaut.2019.102349","article-title":"Multi-omics study in monozygotic twins confirm the contribution of de novo mutation to psoriasis","volume":"106","author":"Li","year":"2020","journal-title":"J. Autoimmun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/19490976.2020.1801964","article-title":"A compromised developmental trajectory of the infant gut microbiome and metabolome in atopic eczema","volume":"12","author":"Ta","year":"2020","journal-title":"Gut Microbes"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1016\/j.jaci.2019.10.030","article-title":"Protein-coding variants contribute to the risk of atopic dermatitis and skin-specific gene expression","volume":"145","author":"Mucha","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1080\/21556660.2019.1619570","article-title":"Epidemiology of atopic dermatitis in Europe","volume":"8","author":"Czarnecka","year":"2019","journal-title":"J. Drug Assess."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.jaci.2011.01.054","article-title":"Contrasting pathogenesis of atopic dermatitis and psoriasis\u2014Part II: Immune cell subsets and therapeutic concepts","volume":"127","author":"Nograles","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.clindermatol.2011.08.019","article-title":"Abnormal epidermal barrier in the pathogenesis of contact dermatitis","volume":"30","author":"Proksch","year":"2012","journal-title":"Clin. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Huerta, C., Rivero, E., and Rodr\u00edguez, L.A.G. (2007). Incidence and Risk Factors for Psoriasis in the General Population. Arch. Dermatol., 143.","DOI":"10.1001\/archderm.143.12.1559"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chang, H.-W., Yan, D., Singh, R., Liu, J., Lu, X., Ucmak, D., Lee, K., Afifi, L., Fadrosh, D., and Leech, J. (2018). Alteration of the cutaneous microbiome in psoriasis and potential role in Th17 polarization. Microbiome, 6.","DOI":"10.1186\/s40168-018-0533-1"},{"key":"ref_28","unstructured":"Calonje, J.E., Brenn, T., Lazar, A.J., and McKee, P.H. (2011). Pathology of the Skin, Elsevier Health Sciences."},{"key":"ref_29","unstructured":"(2020, November 17). Available online: https:\/\/www.mdpi.com\/journal\/ijms\/special_issues\/omics_data_integration."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Graff, M., Scott, R.A., Justice, A.E., Young, K.L., Feitosa, M.F., Barata, L., Winkler, T.W., Chu, A.Y., Mahajan, A., and Hadley, D. (2017). Genome-wide physical activity interactions in adiposity\u2014A meta-analysis of 200,452 adults. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006528"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/4\/1523\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:19:36Z","timestamp":1760159976000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/4\/1523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,3]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["ijms22041523"],"URL":"https:\/\/doi.org\/10.3390\/ijms22041523","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,3]]}}}