TY - JOUR
T1 - Computational gene network analysis reveals TNF-induced angiogenesis
AU - Ogami, Kentaro
AU - Yamaguchi, Rui
AU - Imoto, Seiya
AU - Tamada, Yoshinori
AU - Araki, Hiromitsu
AU - Print, Cristin
AU - Miyano, Satoru
N1 - Funding Information:
Computation time was provided by the Super Computer System, Human Genome Center, The Institute of Medical Science, The University of Tokyo. This work was partially supported by Systems Cancer (Project No 4201), a Grant-in-Aid for Scientific Research on Innovative Areas, by MEXT, Japan. This article has been published as part of BMC Systems Biology Volume 6 Supplement 2, 2012: Proceedings of the 23rd International Conference on Genome Informatics (GIW 2012). The full contents of the supplement are available online at http://www.biomedcentral.com/bmcsystbiol/supplements/ 6/S2.
PY - 2012/12/12
Y1 - 2012/12/12
N2 - Background: TNF (Tumor Necrosis Factor-α) induces HUVEC (Human Umbilical Vein Endothelial Cells) to proliferate and form new blood vessels. This TNF-induced angiogenesis plays a key role in cancer and rheumatic disease. However, the molecular system that underlies TNF-induced angiogenesis is largely unknown.Methods: We analyzed the gene expression changes stimulated by TNF in HUVEC over a time course using microarrays to reveal the molecular system underlying TNF-induced angiogenesis. Traditional k-means clustering analysis was performed to identify informative temporal gene expression patterns buried in the time course data. Functional enrichment analysis using DAVID was then performed for each cluster. The genes that belonged to informative clusters were then used as the input for gene network analysis using a Bayesian network and nonparametric regression method. Based on this TNF-induced gene network, we searched for sub-networks related to angiogenesis by integrating existing biological knowledge.Results: k-means clustering of the TNF stimulated time course microarray gene expression data, followed by functional enrichment analysis identified three biologically informative clusters related to apoptosis, cellular proliferation and angiogenesis. These three clusters included 648 genes in total, which were used to estimate dynamic Bayesian networks. Based on the estimated TNF-induced gene networks, we hypothesized that a sub-network including IL6 and IL8 inhibits apoptosis and promotes TNF-induced angiogenesis. More particularly, IL6 promotes TNF-induced angiogenesis by inducing NF-κB and IL8, which are strong cell growth factors.Conclusions: Computational gene network analysis revealed a novel molecular system that may play an important role in the TNF-induced angiogenesis seen in cancer and rheumatic disease. This analysis suggests that Bayesian network analysis linked to functional annotation may be a powerful tool to provide insight into disease.
AB - Background: TNF (Tumor Necrosis Factor-α) induces HUVEC (Human Umbilical Vein Endothelial Cells) to proliferate and form new blood vessels. This TNF-induced angiogenesis plays a key role in cancer and rheumatic disease. However, the molecular system that underlies TNF-induced angiogenesis is largely unknown.Methods: We analyzed the gene expression changes stimulated by TNF in HUVEC over a time course using microarrays to reveal the molecular system underlying TNF-induced angiogenesis. Traditional k-means clustering analysis was performed to identify informative temporal gene expression patterns buried in the time course data. Functional enrichment analysis using DAVID was then performed for each cluster. The genes that belonged to informative clusters were then used as the input for gene network analysis using a Bayesian network and nonparametric regression method. Based on this TNF-induced gene network, we searched for sub-networks related to angiogenesis by integrating existing biological knowledge.Results: k-means clustering of the TNF stimulated time course microarray gene expression data, followed by functional enrichment analysis identified three biologically informative clusters related to apoptosis, cellular proliferation and angiogenesis. These three clusters included 648 genes in total, which were used to estimate dynamic Bayesian networks. Based on the estimated TNF-induced gene networks, we hypothesized that a sub-network including IL6 and IL8 inhibits apoptosis and promotes TNF-induced angiogenesis. More particularly, IL6 promotes TNF-induced angiogenesis by inducing NF-κB and IL8, which are strong cell growth factors.Conclusions: Computational gene network analysis revealed a novel molecular system that may play an important role in the TNF-induced angiogenesis seen in cancer and rheumatic disease. This analysis suggests that Bayesian network analysis linked to functional annotation may be a powerful tool to provide insight into disease.
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U2 - 10.1186/1752-0509-6-S2-S12
DO - 10.1186/1752-0509-6-S2-S12
M3 - Article
C2 - 23281897
AN - SCOPUS:84878640877
SN - 1752-0509
VL - 6
JO - BMC systems biology
JF - BMC systems biology
IS - SUPPL.2
M1 - S12
ER -
