دورية أكاديمية
أعرض في EDS

Exploring pathway interactions to detect molecular mechanisms of disease: 22q11.2 deletion syndrome.

التفاصيل البيبلوغرافية
العنوان: Exploring pathway interactions to detect molecular mechanisms of disease: 22q11.2 deletion syndrome.
المؤلفون: Shin W; Department of Bioinformatics - BiGCaT, NUTRIM, Maastricht University, Maastricht, 6229 ER, The Netherlands., Kutmon M; Department of Bioinformatics - BiGCaT, NUTRIM, Maastricht University, Maastricht, 6229 ER, The Netherlands.; Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands., Mina E; Leiden University, Leiden, The Netherlands., van Amelsvoort T; Psychiatry & Neuropsychology, MHeNs, Maastricht University, Maastricht, The Netherlands., Evelo CT; Department of Bioinformatics - BiGCaT, NUTRIM, Maastricht University, Maastricht, 6229 ER, The Netherlands.; Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands., Ehrhart F; Department of Bioinformatics - BiGCaT, NUTRIM, Maastricht University, Maastricht, 6229 ER, The Netherlands. friederike.ehrhart@maastrichtuniversity.nl.; Psychiatry & Neuropsychology, MHeNs, Maastricht University, Maastricht, The Netherlands. friederike.ehrhart@maastrichtuniversity.nl.
المصدر: Orphanet journal of rare diseases [Orphanet J Rare Dis] 2023 Oct 24; Vol. 18 (1), pp. 335. Date of Electronic Publication: 2023 Oct 24.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101266602 Publication Model: Electronic Cited Medium: Internet ISSN: 1750-1172 (Electronic) Linking ISSN: 17501172 NLM ISO Abbreviation: Orphanet J Rare Dis Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central, 2006-
مواضيع طبية MeSH: DiGeorge Syndrome*/genetics , Heart Defects, Congenital*, Humans ; Phosphatidylinositol 3-Kinases ; Phenotype ; Gene Expression Profiling
مستخلص: Background: 22q11.2 Deletion Syndrome (22q11DS) is a genetic disorder characterized by the deletion of adjacent genes at a location specified as q11.2 of chromosome 22, resulting in an array of clinical phenotypes including autistic spectrum disorder, schizophrenia, congenital heart defects, and immune deficiency. Many characteristics of the disorder are known, such as the phenotypic variability of the disease and the biological processes associated with it; however, the exact and systemic molecular mechanisms between the deleted area and its resulting clinical phenotypic expression, for example that of neuropsychiatric diseases, are not yet fully understood.
Results: Using previously published transcriptomics data (GEO:GSE59216), we constructed two datasets: one set compares 22q11DS patients experiencing neuropsychiatric diseases versus healthy controls, and the other set 22q11DS patients without neuropsychiatric diseases versus healthy controls. We modified and applied the pathway interaction method, originally proposed by Kelder et al. (2011), on a network created using the WikiPathways pathway repository and the STRING protein-protein interaction database. We identified genes and biological processes that were exclusively associated with the development of neuropsychiatric diseases among the 22q11DS patients. Compared with the 22q11DS patients without neuropsychiatric diseases, patients experiencing neuropsychiatric diseases showed significant overrepresentation of regulated genes involving the natural killer cell function and the PI3K/Akt signalling pathway, with affected genes being closely associated with downregulation of CRK like proto-oncogene adaptor protein. Both the pathway interaction and the pathway overrepresentation analysis observed the disruption of the same biological processes, even though the exact lists of genes collected by the two methods were different.
Conclusions: Using the pathway interaction method, we were able to detect a molecular network that could possibly explain the development of neuropsychiatric diseases among the 22q11DS patients. This way, our method was able to complement the pathway overrepresentation analysis, by filling the knowledge gaps on how the affected pathways are linked to the original deletion on chromosome 22. We expect our pathway interaction method could be used for problems with similar contexts, where complex genetic mechanisms need to be identified to explain the resulting phenotypic plasticity.
(© 2023. Institut National de la Santé et de la Recherche Médicale (INSERM).)
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معلومات مُعتمدة: U01 MH119740 United States MH NIMH NIH HHS
فهرسة مساهمة: Keywords: 22q11.2 deletion syndrome; Copy number variation syndromes; Network analysis; Pathway analysis
المشرفين على المادة: EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
تواريخ الأحداث: Date Created: 20231023 Date Completed: 20231027 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC10594698
DOI: 10.1186/s13023-023-02953-6
PMID: 37872602
قاعدة البيانات: MEDLINE
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