Reconstructing Regulation Networks of Meiosis in Silico

描述（由申请人提供）：在后基因组时代，将基因和蛋白质组织成功能性生物网络至关重要。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，并发现控制这些网络进化的基本原则。该提案的重点是开发新的生物信息学方法，通过整合不同来源的基因组数据，重建调控酵母孢子形成的转录网络，包括减数分裂和孢子形态发生。这些方法是唯一适合于识别转录因子的组合调控，特别是那些短暂的，从而揭示了动态实现的基础网络。这项研究将有助于我们对酵母孢子形成的理解，并可能有助于了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一个很好的起点，为高等生物开发等效的工具。 拟议研究背后的具体假设是，并非所有重要的酵母孢子形成转录调控因子都已确定，许多决定调控逻辑的网络链接仍然缺失。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（定义为由TF、其结合位点和其靶基因组成）; 2.利用上述算法构建芽殖酵母产孢的转录模块，通过组装这些模块发现组合调控，确定酵母产孢的转录网络; 3.基于芽殖酵母网络预测6个新测序的酵母基因组中孢子形成的转录模块和网络拓扑结构。

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.