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

Lucas André Cavalcanti Brandão,Almerinda Agrelli,Luisa Zupin,Paola Maura Tricarico,Sergio Crovella,Ronald Moura,Haissam Abou-Saleh,Rossella Gratton

doi:10.3390/ijms22041523

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.

Highlights

The skin covers the entire human body’s surface and is considered the largest human organ, with an extension of over two square meters in adult individuals, reaching a weight of 4 kg [1]
We developed an omics platform (PlatOMICs) for skin studies that compiles a set of tools and bioinformatics applications that can allow the retrieval of scientific literature data together with the analysis, deciphering, interpretation, and integration of all these sets of information automatically, building networks of molecular interactions and omics meta-analysis
We considered the pivotal role of environmental interactions in the skin, mainly driven by microbiota, as another critical aspect to be examined while dealing with skin diseases

Summary

Introduction

The skin covers the entire human body’s surface and is considered the largest human organ, with an extension of over two square meters in adult individuals, reaching a weight of 4 kg [1]. In order to obtain a general and more complete understanding of the major cellular processes, networks, and genes principally implied in the onset, progression, and risk of PS, Zhao Yuqi and collaborators performed a study that provides the integration of multiple multiomics datasets, such as epigenome-wide association studies (EWAS), genome-wide association studies (GWAS), expression quantitative trait loci, tissue-specific transcriptomics, gene networks, and biological pathway analysis to determine potential targets that are epigenetically and genetically associated with PS risk The output of these results provided a reconfirmation of some of the major pathways already known to correlate with the PS phenotype, including the IL-17 pathway, natural killer T cell function, NO2-dependent, IL-12 pathway, Th1/Th2 axis, JAK/STAT signaling, and cytokine and chemokine signaling, all of which were confirmed in this work to have high enrichment values in terms of associated epigenetic and genetic variants. Phase 1 of PlatOMICs for Skin Diseases with Alterations in the Notch Signaling Pathway

Analysis from the Literature

Analysis from Databases

Findings

Conclusions