Model-based comparative prediction of transcription-factor binding motifs in anabolic responses in bone.
Model-based comparative prediction of transcription-factor binding motifs in anabolic responses in bone.
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DOI：
10.1016/s1672-0229(08)60003-0
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发表时间：
2007-12
影响因子：
9.5
通讯作者：
Liu, Yunlong
中科院分区：
文献类型：
--
作者：
Chen, Andy B.;Hamamura, Kazunori;Wang, Guohua;Xing, Weirong;Mohan, Subburaman;Yokota, Hiroki;Liu, Yunlong
理解控制全局基因表达模式改变的调控机制仍然是计算生物学中的一项具有挑战性的任务。我们以前开发了一个蚂蚁算法，生物启发的计算技术的微阵列数据，并预测假定的转录因子结合基序（TFBM）通过模仿自然蚂蚁的互动行为。在这里，我们将该算法扩展到一套基于Web的软件，蚂蚁建模，并将其应用于研究骨形成的转录机制。机械负荷和骨形态发生蛋白（BMP）的管理是两个已知的治疗，以加强骨。我们提出了一个问题：是否有任何TFBM刺激“机械负荷的合成代谢反应”和“BMP介导的成骨信号”？虽然在这两种反应中的基因之间没有显著的重叠，但基于模型的比较分析表明，这两个独立的成骨过程采用共同的TFBM，如应激反应元件和过氧化物酶体增殖物激活受体（PPAR）的基序。使用小鼠成骨细胞的体外建模后分析支持预测的TFBM如PPAR、Ikaros 3和LMO 2参与对机械负荷的响应。两者合计，这些结果将是有用的，以获得一组可检验的假设，并检查在复杂的骨形成的转录控制的特定监管机构的作用。
Understanding the regulatory mechanism that controls the alteration of global gene expression patterns continues to be a challenging task in computational biology. We previously developed an ant algorithm, a biologically-inspired computational technique for microarray data, and predicted putative transcription-factor binding motifs (TFBMs) through mimicking interactive behaviors of natural ants. Here we extended the algorithm into a set of web-based software, Ant Modeler, and applied it to investigate the transcriptional mechanism underlying bone formation. Mechanical loading and administration of bone morphogenic proteins (BMPs) are two known treatments to strengthen bone. We addressed a question: Is there any TFBM that stimulates both “anabolic responses of mechanical loading” and “BMP-mediated osteogenic signaling”? Although there is no significant overlap among genes in the two responses, a comparative model-based analysis suggests that the two independent osteogenic processes employ common TFBMs, such as a stress responsive element and a motif for peroxisome proliferator-activated receptor (PPAR). The post-modeling in vitro analysis using mouse osteoblast cells supported involvements of the predicted TFBMs such as PPAR, Ikaros 3, and LMO2 in response to mechanical loading. Taken together, the results would be useful to derive a set of testable hypotheses and examine the role of specific regulators in complex transcriptional control of bone formation.
影响因子：
4.4
作者：
Liu, Yunlong;Yokota, Hiroki
通讯作者：
Yokota, Hiroki