Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Prioritization of genes involved in endothelial cell apoptosis by their implication in lymphedema using an analysis of associative gene networks with ANDSystem. / Saik, Olga V.; Nimaev, Vadim V.; Usmonov, Dilovarkhuja B. и др.
в: BMC Medical Genomics, Том 12, № Suppl 2, 47, 13.03.2019, стр. 47.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Prioritization of genes involved in endothelial cell apoptosis by their implication in lymphedema using an analysis of associative gene networks with ANDSystem
AU - Saik, Olga V.
AU - Nimaev, Vadim V.
AU - Usmonov, Dilovarkhuja B.
AU - Demenkov, Pavel S.
AU - Ivanisenko, Timofey V.
AU - Lavrik, Inna N.
AU - Ivanisenko, Vladimir A.
PY - 2019/3/13
Y1 - 2019/3/13
N2 - Background: Currently, more than 150 million people worldwide suffer from lymphedema. It is a chronic progressive disease characterized by high-protein edema of various parts of the body due to defects in lymphatic drainage. Molecular-genetic mechanisms of the disease are still poorly understood. Beginning of a clinical manifestation of primary lymphedema in middle age and the development of secondary lymphedema after treatment of breast cancer can be genetically determined. Disruption of endothelial cell apoptosis can be considered as one of the factors contributing to the development of lymphedema. However, a study of the relationship between genes associated with lymphedema and genes involved in endothelial apoptosis, in the associative gene network was not previously conducted. Methods: In the current work, we used well-known methods (ToppGene and Endeavour), as well as methods previously developed by us, to prioritize genes involved in endothelial apoptosis and to find potential participants of molecular-genetic mechanisms of lymphedema among them. Original methods of prioritization took into account the overrepresented Gene Ontology biological processes, the centrality of vertices in the associative gene network, describing the interactions of endothelial apoptosis genes with genes associated with lymphedema, and the association of the analyzed genes with diseases that are comorbid to lymphedema. Results: An assessment of the quality of prioritization was performed using criteria, which involved an analysis of the enrichment of the top-most priority genes by genes, which are known to have simultaneous interactions with lymphedema and endothelial cell apoptosis, as well as by genes differentially expressed in murine model of lymphedema. In particular, among genes involved in endothelial apoptosis, KDR, TNF, TEK, BMPR2, SERPINE1, IL10, CD40LG, CCL2, FASLG and ABL1 had the highest priority. The identified priority genes can be considered as candidates for genotyping in the studies involving the search for associations with lymphedema. Conclusions: Analysis of interactions of these genes in the associative gene network of lymphedema can improve understanding of mechanisms of interaction between endothelial apoptosis and lymphangiogenesis, and shed light on the role of disturbance of these processes in the development of edema, chronic inflammation and connective tissue transformation during the progression of the disease.
AB - Background: Currently, more than 150 million people worldwide suffer from lymphedema. It is a chronic progressive disease characterized by high-protein edema of various parts of the body due to defects in lymphatic drainage. Molecular-genetic mechanisms of the disease are still poorly understood. Beginning of a clinical manifestation of primary lymphedema in middle age and the development of secondary lymphedema after treatment of breast cancer can be genetically determined. Disruption of endothelial cell apoptosis can be considered as one of the factors contributing to the development of lymphedema. However, a study of the relationship between genes associated with lymphedema and genes involved in endothelial apoptosis, in the associative gene network was not previously conducted. Methods: In the current work, we used well-known methods (ToppGene and Endeavour), as well as methods previously developed by us, to prioritize genes involved in endothelial apoptosis and to find potential participants of molecular-genetic mechanisms of lymphedema among them. Original methods of prioritization took into account the overrepresented Gene Ontology biological processes, the centrality of vertices in the associative gene network, describing the interactions of endothelial apoptosis genes with genes associated with lymphedema, and the association of the analyzed genes with diseases that are comorbid to lymphedema. Results: An assessment of the quality of prioritization was performed using criteria, which involved an analysis of the enrichment of the top-most priority genes by genes, which are known to have simultaneous interactions with lymphedema and endothelial cell apoptosis, as well as by genes differentially expressed in murine model of lymphedema. In particular, among genes involved in endothelial apoptosis, KDR, TNF, TEK, BMPR2, SERPINE1, IL10, CD40LG, CCL2, FASLG and ABL1 had the highest priority. The identified priority genes can be considered as candidates for genotyping in the studies involving the search for associations with lymphedema. Conclusions: Analysis of interactions of these genes in the associative gene network of lymphedema can improve understanding of mechanisms of interaction between endothelial apoptosis and lymphangiogenesis, and shed light on the role of disturbance of these processes in the development of edema, chronic inflammation and connective tissue transformation during the progression of the disease.
KW - ANDSystem
KW - Associative gene networks
KW - Endothelial cell apoptosis
KW - Gene prioritization
KW - Lymphedema
KW - HEPATOCYTE GROWTH-FACTOR
KW - SECONDARY LYMPHEDEMA
KW - CD40 LIGAND
KW - RECEPTOR
KW - VEGF-C
KW - CYTOKINE
KW - CANCER
KW - INTERLEUKIN-10 EXPRESSION
KW - TNF-ALPHA
KW - INNATE IMMUNITY
UR - http://www.scopus.com/inward/record.url?scp=85063005050&partnerID=8YFLogxK
U2 - 10.1186/s12920-019-0492-9
DO - 10.1186/s12920-019-0492-9
M3 - Article
C2 - 30871556
AN - SCOPUS:85063005050
VL - 12
SP - 47
JO - BMC Medical Genomics
JF - BMC Medical Genomics
SN - 1755-8794
IS - Suppl 2
M1 - 47
ER -
ID: 18860354