Integrative Analysis of Public RNA-seq Repositories

描述（申请人提供）：最近，RNA-seq技术越来越多地取代微阵列进行表达谱分析。在本提案中，我们将及时应对快速积累的RNA-seq数据带来的新挑战和机遇。我们将设计新的方法来对许多RNA-seq数据集进行整合分析，以研究选择性剪接的功能和调控。具体而言，我们有以下具体目标：(1)我们将开发一种新的基于图的模式挖掘方法来重建拼接模块的图谱，并确定人类，小鼠，苍蝇和酵母的相关实验条件。(2)我们将利用RNA-seq数据提供的表达和剪接信息，研究转录和剪接这两个重要调控过程之间的耦合。我们将设计一种新的多层网络挖掘方法来系统地识别偶联转录剪接模块。(3)我们将预测交替拼接的函数

DESCRIPTION (provided by applicant): Recently, the RNA-seq technology is increasingly replacing microarray for expression profiling. In this proposal, we will timely address the emerging challenges and opportunities brought by the rapidly accumulating RNA-seq data. We will design novel methods to perform integrative analysis of many RNA-seq datasets to study the functions and regulations of alternative splicing. In particular, we have the following specifi aims: (1) We will develop a novel graph- based pattern mining method to reconstruct an atlas of splicing modules and identify the associated experimental conditions in human, mouse, fly, and yeast. (2) We will study the coupling between transcription and splicing, the two important regulatory processes, by exploiting both expression and splicing information provided by RNA-seq data. We will design a novel multi-layer network mining approach to systematically identify coupled transcription- splicing modules. (3) We will predict the functions of alternatively spliced transcripts to establish a high-resolution function annotation of human genome. The predicted functions will be incorporated into the GeneOntology and the Ensembl databases to benefit the biological community. (4) We will perform experimental validation on a subset of computational predictions made in Aims 1, 2, 3. (5) We will develop web databases and software to directly benefit the scientific community. Our methods and software will significantly facilitate the re-use of the vast amount of existing RNA-seq data, reduce the necessity to generate new data, and improve our understanding of gene regulations under a variety of perturbations.