A network model for angiogenesis in ovarian cancer.
A network model for angiogenesis in ovarian cancer.
复制标题
DOI：
10.1186/s12859-015-0551-y
复制
发表时间：
2015-04-11
影响因子：
3
通讯作者：
Yuan GC
中科院分区：
文献类型：
--
作者：
Glass K;Quackenbush J;Spentzos D;Haibe-Kains B;Yuan GC
我们最近发现了两种强大的卵巢癌亚型，通过参与血管生成的基因表达来定义，在临床结果上有显着差异。为了确定区分亚型的潜在调控机制，我们应用了PANDA，这是一种使用综合方法来模拟基因调控网络中信息流的方法。我们发现在血管生成和非血管生成亚型中活跃的网络之间存在明显差异，主要由一组关键转录因子定义，尽管先前报道在血管生成中发挥作用，但在亚型之间没有强烈的差异表达。我们的网络分析表明，这些因子参与了两种亚型中不同基因的激活（或抑制），导致其网络靶标的差异表达。介导亚型之间差异的机制包括以前未被认识到的促进血管生成的作用，增加全基因组DNA甲基化和复杂的组合调控模式。我们开发的模型要求我们改变对生物网络中驱动因素的解释，从基因本身转向它们之间的相互作用。观察到的亚型之间的调节变化表明治疗干预可能有助于卵巢癌的治疗。本文的在线版本（doi：10.1186/s12859-015-0551-y）包含补充材料，可供授权用户使用。
We recently identified two robust ovarian cancer subtypes, defined by the expression of genes involved in angiogenesis, with significant differences in clinical outcome. To identify potential regulatory mechanisms that distinguish the subtypes we applied PANDA, a method that uses an integrative approach to model information flow in gene regulatory networks. We find distinct differences between networks that are active in the angiogenic and non-angiogenic subtypes, largely defined by a set of key transcription factors that, although previously reported to play a role in angiogenesis, are not strongly differentially-expressed between the subtypes. Our network analysis indicates that these factors are involved in the activation (or repression) of different genes in the two subtypes, resulting in differential expression of their network targets. Mechanisms mediating differences between subtypes include a previously unrecognized pro-angiogenic role for increased genome-wide DNA methylation and complex patterns of combinatorial regulation. The models we develop require a shift in our interpretation of the driving factors in biological networks away from the genes themselves and toward their interactions. The observed regulatory changes between subtypes suggest therapeutic interventions that may help in the treatment of ovarian cancer. The online version of this article (doi:10.1186/s12859-015-0551-y) contains supplementary material, which is available to authorized users.
登录
查看更多内容
DOI：
10.1158/1078-0432.ccr-13-0489
发表时间：
2013-09-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Collinson F;Hutchinson M;Craven RA;Cairns DA;Zougman A;Wind TC;Gahir N;Messenger MP;Jackson S;Thompson D;Adusei C;Ledermann JA;Hall G;Jayson GC;Selby PJ;Banks RE
通讯作者：
Banks RE
影响因子：
3.8
作者：
Carlson, Erik A.;McCulloch, Colin;Silkworth, Jay B.
通讯作者：
Silkworth, Jay B.
影响因子：
4.8
作者：
Carlos Roman, Angel;Carvajal-Gonzalez, Jose M.;Fernandez-Salguero, Pedro M.
通讯作者：
Fernandez-Salguero, Pedro M.
影响因子：
8
作者：
Cardoso, Rosa;Love, Robert;Brooun, Alexei
通讯作者：
Brooun, Alexei
影响因子：
20.3
作者：
Aurora, Aryn B.;Biyashev, Dauren;Volpert, Olga V.
通讯作者：
Volpert, Olga V.