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AuthorBrandão, Lucas André Cavalcanti
AuthorMoura, Ronald Rodrigues de
AuthorMarzano, Angelo Valerio
AuthorMoltrasio, Chiara
AuthorTricarico, Paola Maura
AuthorCrovella, Sergio
Available date2022-03-07T08:54:12Z
Publication Date2022-02-18
Publication NameInternational Journal of Molecular Sciences
Identifierhttp://dx.doi.org/10.3390/ijms23042278
CitationBrandao, Lucas A.C., Ronald R.d. Moura, Angelo V. Marzano, Chiara Moltrasio, Paola M. Tricarico, and Sergio Crovella. 2022. "Variant Enrichment Analysis to Explore Pathways Functionality in Complex Autoinflammatory Skin Disorders through Whole Exome Sequencing Analysis" International Journal of Molecular Sciences 23, no. 4: 2278. https://doi.org/10.3390/ijms23042278
URIhttp://hdl.handle.net/10576/27721
AbstractThe challenge of unravelling the molecular basis of multifactorial disorders nowadays cannot rely just on association studies searching for potential causative variants shared by groups of patients and not present in healthy individuals; indeed, association studies have as a main limitation the lack of information on the interactions between the disease-causing variants. Thus, new genomic analysis tools focusing on disrupted pathways rather than associated gene variants are required to better understand the complexity of a disease. Therefore, we developed the Variant Enrichment Analysis (VEA) workflow, a tool applicable for whole exome sequencing data, able to find differences between the numbers of genetic variants in a given pathway in comparison with a reference dataset. In this study, we applied VEA to discover novel pathways altered in patients with complex autoinflammatory skin disorders, namely PASH ( = 9), 3 of whom are overlapping with SAPHO) and PAPASH ( = 3). With this approach we have been able to identify pathways related to neutrophil and endothelial cells homeostasis/activations, as disrupted in our patients. We hypothesized that unregulated neutrophil transendothelial migration could elicit increased neutrophil infiltration and tissue damage. Based on our findings, VEA, in our experimental dataset, allowed us to predict novel pathways impaired in subjects with autoinflammatory skin disorders.
Languageen
PublisherMDPI
SubjectOMICs
PAPASH
PASH
SAPHO
hidradenitis suppurativa
whole exome sequencing
TitleVariant Enrichment Analysis to Explore Pathways Functionality in Complex Autoinflammatory Skin Disorders through Whole Exome Sequencing Analysis.
TypeArticle
Issue Number4
Volume Number23
dc.accessType Open Access


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