MiRNA and RNA-binding proteins as integral part of cell communication:context-based target prediction and validation

miRNA的调节活性受到其他miRNA和RNA结合蛋白的存在的显著影响。目前正在开发考虑miRNA和RBP之间的确切位置和关系类型（合作或拮抗）的定量方法。目前大多数用于miRNA靶预测的方法仅利用靶区域附近的信息。缺点是缺乏不同实验来源的整合，以及对问题的局部看法，这些问题没有考虑到完整mRNA分子的全面代表性。由于这些原因，我们将开发技术，1。通过迭代计算改进产生实验数据，其提供amiRNA介导的靶RNA切割和mRNA-RNA结合蛋白相互作用位点的参数，2.以连贯和有原则的方式整合不同的实验数据源，这些数据源专注于mRNA分子和miRNA-mRNA或RBP-mRNA相互作用的各个方面，例如：来自dsRNA-seq实验的mRNA二级结构、来自CLIP-seq实验的RBP结合、来自PAR-CL实验的占用曲线，3.从mRNA分子的全局角度进行研究。这将使我们能够深入了解基因表达的不同调控机制（RBP，miRNA）的相关作用，指导mRNA分子全局视角的信息编码设计。

The regulatory activity of miRNAs is significantly affected by the presence of other miRNAs and RNA binding proteins. Quantitative methods that take the exact location and the type of relation (cooperative or antagonist) between miRNAs and RBPs into account are currently being developed. Most current approaches for miRNA target prediction exploit only information in the vicinity of target regions. Shortcomings are the lack of integration of diverse experimental sources, and local views of problems which do not take into account a comprehensive representation of the full mRNA molecule. For these reasons we will develop techniques that 1. generate experimental data by iterative computational improvement that provide parameters for amiRNA mediated target RNA cleavage and mRNA-RNA binding protein interaction sites, 2. integrate in a coherent and principled way the different experimental data sources that focus on various aspects of mRNA molecules and miRNA-mRNA or RBP-mRNA interactions, such as: secondary structure of mRNA from dsRNA-seq experiments, RBP binding from CLIP-seq experiments, occupancy profile from PAR-CL experiments, 3. work using a global perspective on the mRNA molecule. This will allow us to gain insight into the correlated action of different regulatory mechanisms (RBPs, miRNAs) of gene expression guiding the design of the information encoding for the global perspective on the mRNA molecule.