Integrative Systems Biology Investigation of Fabry Disease
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 includin...
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doaj-b4dd247968a54bf0897518792da2fdab2020-11-24T22:28:10ZengMDPI AGDiseases2079-97212016-11-01443510.3390/diseases4040035diseases4040035Integrative Systems Biology Investigation of Fabry DiseaseMarco Fernandes0Holger Husi1Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UKInstitute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UKFabry 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.http://www.mdpi.com/2079-9721/4/4/35Anderson-Fabry Diseaseomicsdata integrationdisease modelling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marco Fernandes Holger Husi |
spellingShingle |
Marco Fernandes Holger Husi Integrative Systems Biology Investigation of Fabry Disease Diseases Anderson-Fabry Disease omics data integration disease modelling |
author_facet |
Marco Fernandes Holger Husi |
author_sort |
Marco Fernandes |
title |
Integrative Systems Biology Investigation of Fabry Disease |
title_short |
Integrative Systems Biology Investigation of Fabry Disease |
title_full |
Integrative Systems Biology Investigation of Fabry Disease |
title_fullStr |
Integrative Systems Biology Investigation of Fabry Disease |
title_full_unstemmed |
Integrative Systems Biology Investigation of Fabry Disease |
title_sort |
integrative systems biology investigation of fabry disease |
publisher |
MDPI AG |
series |
Diseases |
issn |
2079-9721 |
publishDate |
2016-11-01 |
description |
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. |
topic |
Anderson-Fabry Disease omics data integration disease modelling |
url |
http://www.mdpi.com/2079-9721/4/4/35 |
work_keys_str_mv |
AT marcofernandes integrativesystemsbiologyinvestigationoffabrydisease AT holgerhusi integrativesystemsbiologyinvestigationoffabrydisease |
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