Integrative systems biology investigation of Fabry disease

Fernandes, M. and Husi, H. (2016) Integrative systems biology investigation of Fabry disease. Diseases, 4(4), 35. (doi: 10.3390/diseases4040035)

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Abstract

Fabry disease (FD) is a rare X-linked recessive genetic disorder caused by a deficient activity of the lysosomal enzyme alpha-galactosidase A (GLA) and is characterised by intra-lysosomal accumulation of globotriaosylceramide (Gb3). We performed a meta-analysis of peer-reviewed publications including high-throughput omics technologies including naïve patients and those undergoing enzyme replacement therapy (ERT). This study describes FD on a systems level using a systems biology approach, in which molecular data sourced from multi-omics studies is extracted from the literature and integrated as a whole in order to reveal the biochemical processes and molecular pathways potentially affected by the dysregulation of differentially expressed molecules. In this way new insights are provided that describe the pathophysiology of this rare disease. Using gene ontology and pathway term clustering, FD displays the involvement of major biological processes such as the acute inflammatory response, regulation of wound healing, extracellular matrix (ECM) remodelling, regulation of peptidase activity, and cellular response to reactive oxygen species (ROS). Differential expression of acute-phase response proteins in the groups of naïve (up-regulation of ORM1, ORM2, ITIH4, SERPINA3 and FGA) and ERT (down-regulation of FGA, ORM1 and ORM2) patients could be potential hallmarks for distinction of these two patient groups.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Fernandes, Mr Marco and Husi, Dr Holger
Authors: Fernandes, M., and Husi, H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Diseases
Publisher:MDPI
ISSN:2079-9721
ISSN (Online):2079-9721
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Diseases 4(4): 35
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
637441IMODE-CKD: Clinical and system-omics for the identification of the Molecular Determinants of established Chronic Kidney DiseaseHolger HusiEuropean Commission (EC)608332RI CARDIOVASCULAR & MEDICAL SCIENCES