Almughrbi Aya Hamad, Crovella Sergio
Biological Science Program, Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha, Qatar.
Exp Dermatol. 2022 Sep;31 Suppl 1:9-16. doi: 10.1111/exd.14581.
If we try to describe the search for molecular actors involved in inflammatory diseases, the picture best representing this task is a mission to unexplored worlds. However, researchers nowadays have powerful tools to support this journey to the complexity of the unknown: Next generation Sequencing technologies have provided a plethora of data describing the different OMICs possibly involved in the different inflammatory diseases. Here, we focused on autoinflammatory skin diseases showing the progress of OMICs-related findings in the understanding of Syndromic HS pathogenesis. We described the studies reporting possible genotype/phenotype correlation in PASH and PAPASH patients (both unrelated or familial cases), highlighting those just genetic variations associated with the diseases have been observed, but the information on common pathways shared by PASH and PAPASH patients were lacking, thus rendering difficult to decipher the common molecular basis of these autoinflammatory conditions. Aimed at filling this gap of knowledge, we proposed an integrated OMICs approach able to identify common pathways shared by subjects suffering from PASH and PAPASH: pathway-based whole sequencing analysis allowed the identification of 4 pathways, keratinization, formation of the cornified envelope steroid metabolism and Vitamin D metabolism, disrupted in PASH and PAPASH patients. Finally, we mentioned the novel bioinformatic platform, named PlatOMICs, capable of integrating OMICs experimental findings also with the ones already reported in public repositories supporting the efforts of the researchers and clinicians to discover molecular pathways shared by individuals suffering of a disease, confronting and integrating the bench findings with the in-silico ones.
如果我们试图描述对参与炎症性疾病的分子因素的探索，最能代表这项任务的图景就是一次对未知世界的探索之旅。然而，如今研究人员拥有强大的工具来支持这次通向未知复杂性的旅程：新一代测序技术提供了大量数据，描述了可能与不同炎症性疾病相关的各种组学。在这里，我们聚焦于自身炎症性皮肤病，展示了与组学相关的研究结果在理解综合征性化脓性汗腺炎发病机制方面的进展。我们描述了报告PASH和PAPASH患者（包括散发性或家族性病例）中可能的基因型/表型相关性的研究，强调虽然已经观察到与这些疾病相关的基因变异，但缺乏关于PASH和PAPASH患者共同通路的信息，因此难以解读这些自身炎症性疾病的共同分子基础。为了填补这一知识空白，我们提出了一种综合组学方法，能够识别PASH和PAPASH患者共有的共同通路：基于通路的全基因组测序分析确定了4条通路，即角质化、角质包膜形成、类固醇代谢和维生素D代谢，在PASH和PAPASH患者中这些通路受到破坏。最后，我们提到了一个名为PlatOMICs的新型生物信息学平台，它能够将组学实验结果与公共数据库中已报告的结果整合起来，支持研究人员和临床医生发现疾病患者共有的分子通路，将实验室研究结果与计算机模拟结果进行对比和整合。
