Reconstructing Regulation Networks of Meiosis in Silico

描述(申请人提供)：在后基因组时代，将基因和蛋白质组织成功能生物网络是至关重要的。我们的长期目标是剖析调控细胞中每个生物过程的转录调控网络，了解调控机制，并发现支配这些网络进化的基本原理。这一建议的重点是开发新的生物信息学方法，通过整合来自不同来源的基因组数据来重建调控酵母孢子形成的转录网络，该网络包括减数分裂和孢子形态发生。这些方法特别适合于识别转录因子的组合调控，特别是那些瞬时转录因子，从而揭示潜在网络的动态实现。这项拟议的研究将有助于我们对酵母产孢子的理解，并可能有助于理解高等生物的减数分裂。在拟议的研究中开发和验证的生物信息学方法也可以作为开发适用于高等生物的同等工具的一个很好的起点。 这项拟议的研究背后的具体假设是，并不是所有酵母孢子形成的重要转录调控因子都被确定，而且许多决定调控逻辑的网络联系仍然缺失。其具体目标是：1.发展一种新的生物信息学方法，利用基因表达、转录因子结合和序列基序信息准确构建转录模块(由一个转铁蛋白、其结合部位及其靶基因组成)；2.利用上述算法构建芽殖酵母产孢量的转录模块，通过组装这些模块发现组合调控并确定酵母产孢量的转录网络；3.根据芽孢酵母基因组的网络预测新测序的6个酵母基因组中产孢量的转录模块和网络拓扑。

DESCRIPTION (provided by applicant): In the post-genome era, it is critical to organize genes and proteins into functional biological networks. Our long-term goal is to dissect the transcriptional regulatory networks that regulate every biological process in the cell, understand the regulatory mechanisms, and discover fundamental principles that govern the evolution of these networks. The focus of this proposal is to develop new bioinformatics methods for reconstructing the transcriptional network regulating yeast sporulation, which consists of meiosis and spore morphogenesis, by integrating genomic data from different sources. These methods are uniquely appropriate for identifying combinatorial regulation of transcription factors particularly those transient ones and thus revealing the dynamic realization of the underlying network. The proposed research will contribute significantly to our understanding of yeast sporulation and may shed light on understanding meiosis in higher organisms. The bioinformatics methods developed and validated in the proposed study can also serve as a good starting point to develop equivalent tools for higher organisms. The specific hypothesis behind the proposed research is that not all important transcriptional regulators of yeast sporulation have been identified, and many network links that determine regulatory logic are still missing. The specific aims are: 1. develop a new bioinformatics method to accurately construct transcription modules (defined to consist of a TF, its binding site and its target genes) using gene expression, transcription factor binding and sequence motif information; 2. construct transcription modules of budding yeast sporulation using the above algorithm, discover combinatorial regulation and determine transcriptional network of yeast sporulation by assembling these modules; 3. predict transcription modules and network topologies of sporulation in the 6 newly sequenced yeast genomes based on the network of budding yeast.