Bachelor/master dissertation (Dissertations and theses)
Network-based Approach Enabling Drug Repositioning for the Treatment of Myocardial Infarction
Androsova, Ganna
2014
 

Files


Full Text
MS Thesis - Androsova Ganna.pdf
Author postprint (2.12 MB)
Download

All documents in ORBilu are protected by a user license.

Send to



Details



Keywords :
myocardial infarction; cryoinjury; zebrafish model; WGCNA; heart regeneration
Abstract :
[en] Despite a notable reduction in incidence of acute myocardial infarction (MI), patients who experience it remain at risk for premature death and cardiac malfunction. The human cardiomyocytes are not able to achieve extensive regeneration upon MI. Remarkably, the adult zebrafish is able to achieve complete heart regeneration following amputation, cryoinjury or genetic ablation. This raises new potential opportunities on how to boost the heart healing capacity in humans. The objective of our research is to characterize the transcriptional network of the zebrafish heart regeneration, to describe underlying regulatory mechanisms, and to identify potential drugs capable to boost heart regeneration capacity. Having identified the gene co-expression patterns in the data from a zebrafish cryoinjury model, we constructed a weighted gene co-expression network. To detect candidate functional sub-networks (modules), we used two different network clustering approaches: a density-based (ClusterONE) and a topological overlap-based (Dynamic Hybrid) algorithms. We identified eighteen distinct modules associated with heart recovery upon cryoinjury. Functional enrichment analysis displayed that the modules are involved in different cellular processes crucial for heart regeneration, including: cell fate specification (p-value < 0.006) and migration (p-value < 0.047), cardiac cell differentiation (p-value < 3E-04), and various signaling events (p-value < 0.037). The visualization of the modules’ expression profiles confirmed the relevance of these functional enrichments. Among the candidate hub genes detected in the network, there are genes relevant to atherosclerosis treatment and inflammation during cardiac arrest. Among the top candidate drugs, there were drugs already reported to play therapeutic roles in heart disease, though the majority of the drugs have not been considered yet for myocardial infarction treatment. In conclusion, our findings provide insights into the complex regulatory mechanisms involved during heart regeneration in the zebrafish. These data will be useful for modeling specific network-based responses to heart injury, and for finding sensitive network points that may trigger or boost heart regeneration in the zebrafish, and possibly in mammals.
Research center :
CRP SANTE - Centre de Recherche Public de la Santé
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Androsova, Ganna ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Language :
English
Title :
Network-based Approach Enabling Drug Repositioning for the Treatment of Myocardial Infarction
Defense date :
17 July 2014
Number of pages :
73
Institution :
Unilu - University of Luxembourg, Luxembourg, Luxembourg
Degree :
Master in Integrated Systems Biology (Académique)
Promotor :
Azuaje, Francisco
Schneider, Reinhard 
Jury member :
Nazarov, Petr
Krause, Roland  
Name of the research project :
INFUSED
Funders :
FNR - Fonds National de la Recherche [LU]
Available on ORBilu :
since 20 January 2015

Statistics


Number of views
196 (21 by Unilu)
Number of downloads
297 (15 by Unilu)

Bibliography


Similar publications



Contact ORBilu