白血病多层次转录调控组学数据的信息整合与可视化挖掘

项目名称： 白血病多层次转录调控组学数据的信息整合与可视化挖掘

项目编号： No.31301041

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 方海

作者单位： 上海交通大学

项目金额： 20万元

中文摘要： 白血病的发生发展不仅涉及基因突变、染色体易位形成的融合蛋白等遗传学改变，而且还涉及DNA甲基化、组蛋白修饰等表观遗传学机制。高通量组学技术为研究白血病提供技术保障与多层次转录调控组学数据，但同时也给相应的信息整合与挖掘带来了巨大的挑战，如数据本身假阳性与假阴性、转录调控与表观修饰关系难以界定等。本项目拟在前期自主开发并在解析多个生物学模型的机制方面展现出多种优势的基础上，利用自组织图（Self-organizing map）在规律性模式识别、去除干扰信号与多维可视化展示的特色，结合各种信息注解、调控元件等数据库，建立一套较完备的多层次组学信息整合与可视化挖掘框架，重点解析项目组已积累的白血病关键转录因子结合位点、各种组蛋白表观修饰、转录表达水平之间内在的关系。同时，应用该系统进一步挖掘若干组蛋白修饰与基因表达的联合标识，分析并实验验证其在白血病病人样本中的潜在临床价值。

中文关键词： 白血病；转录调控组学；大数据分析；自组织展示；

英文摘要： The initiation and progression of leukemia is not only driven by the genetic changes such as gene mutations and chromosomal translocations, but is also under the control of epigenetic regulations that involve DNA methylation and chemical markers on core histone tails. The advances of the high-throughput technologies revolutionize the studies on leukemogenesis, allowing for various biological data produced in parallel and on a genome scale (omics). However, it still remains a great challenge to make sense of these multi-layer omics data. Such challenge is largely due to the noisy nature of data and the difficulty in clearly defining causative relationships between histone modifications and regulatory outcome. In this regard, the self-organizing map (SOM) is particularly useful, as we have shown previously, for topology-preserving characterization of multi-dimensional omics data. As proposed here, we aim to establish a SOM-centric analytical pipeline and web server for maximizing its beneficial potentials in visualizing, clustering and integrating omics data of various types. Using the proposed pipeline together with databases of ontologies and regulatory elements, we also aim to decode the inherent relationships among multi-layer regulatory omics data in leukemia, including but not limited to key transcription fa

英文关键词： Leukemia；Regulatory genomics；Big data analytics；Self-organised representation；