Multiomics Integration in Skin Diseases with Alterations in Notch Signaling Pathway: PlatOMICs Phase 1 Deployment

Abstract

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–Oliver 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.

Transcriptome Meta-Analysis Confirms the Hidradenitis Suppurativa Pathogenic Triad: Upregulated Inflammation, Altered Epithelial Organization, and Dysregulated Metabolic Signaling

“…We searched Sequence Read Archive (SRA) [ 18 ] and Gene Expression Omnibus (GEO) [ 19 ] datasets on 11 July 2022, to find studies involving RNA-Seq of HS tissue samples. The search keywords were: ((Hidradenitis Suppurativa) OR (Acne Inversa)) AND ((RNA-Seq) OR (Transcriptome)) [ 20 ]. After removing duplicates, we included studies that met the criteria of: experiments carried out in HS patients’ skin ( Homo sapiens organism filter); had matching healthy skin controls; and had raw data (fastq files) available for each sample.…”

The Genomic Architecture of Hidradenitis Suppurativa—A Systematic Review

“…The significance of GSC variants and the disruption in Notch signaling pathways and its targets in HS, is still evolving. Further functional and multiomic studies are required to determine the definitive role of the Notch signaling pathway in skin disease, including HS ( Brandão et al, 2021 ). A working model of HS pathophysiology suggests that underlying genetic variants lead to lower protein expression which becomes functionally relevant under cellular stress mediated by friction (obesity), temperature and dysbiosis ( Pink et al, 2016 ).…”

Variant Enrichment Analysis to Explore Pathways Functionality in Complex Autoinflammatory Skin Disorders through Whole Exome Sequencing Analysis

“…Recently, we launched a multi-omics platform (PlatOMICs), an integrative web platform for analyzing omics (or multi-omics) data, to unravel the molecular pathogenesis of human disorders [28]. Unfortunately, since no skin biopsy from our patients was available, we could not apply this integrative analysis.…”