Incorporating microRNA data and analyses into the leading cancer genomics portal

描述（由申请人提供）：微小RNA（miRNA）是通过调节信使（mRNA）翻译来控制基因表达的小的非编码RNA。miRNA可以作为癌基因或肿瘤抑制因子，并且miRNA的差异表达与癌症诊断、分期和预后相关，并且已经用于提名治疗靶点。关于癌症中miRNA的大部分已知信息来自基因组规模的miRNA表达谱。不幸的是，尽管有数百项已发表的使用miRNA谱数据的研究，但目前基本的癌症生物学家缺乏工具来调查特定癌症类型中一种或多种miRNA的差异表达或miRNA表达谱研究的全球集合。障碍包括确定可用数据、平台异质性、分析方法和有意义的结果呈现。因此，一个有用的解决方案必须解决许多挑战，包括越来越多的miRNA，用于测量miRNA表达的多种技术和报告基因，不同的临床和实验事实，以及产生生物学意义的分析。在这里，我们建议为生物学家开发一种解决方案，寻求在全球癌症miRNA数据集的集合中探索单个miRNA或miRNA签名。为了实现这一目标，我们的总体目标是收集所有公开可用的癌症相关高通量miRNA数据，在三个层面上标准化不同的数据-样本数据，表达数据和统计分析-并以一致，可比的格式呈现数据，该格式也与Oncomine中现有的mRNA和DNA拷贝数据完全整合。在第一阶段，我们将1）为3个micro-RNA谱数据集建立并实施样本元数据策展策略，以证明将受控词汇和本体应用于miRNA样本元数据的可行性; 2）为3个micro-RNA谱数据集建立并实施平台映射策略，以证明将不同的miRNA平台标准化为单一、统一格式的可行性; 3）对3个微RNA谱数据集进行差异表达分析，以证明在目标1和2中进行的策展和作图步骤之后创建自动标准化分析的可行性。在第一阶段成功完成后，我们提出了以下第二阶段目标：1）开发和实施一个可扩展的过程，用于捕获和管理micro-RNA基因组学数据，并通过开发软件集成到Oncomine中，以支持miRNA样本数据的可扩展目录和捕获; 2）开发可扩展的micro-RNA基因组学平台映射和数据仓库策略，并集成到Oncomine中，通过开发工具以适应微RNAS的动态命名约定并映射到共同标识符，以及3）开发用于分析微RNA谱数据集的自动化分析方法并通过开发跨miRNA数据库的自动化差异表达、共表达、离群值和Meta分析能力整合到Oncomine中，并整合到已建立的Oncomine数据库中。 公共卫生相关性：尽管科学家为了解癌症的分子基础做出了巨大努力，但这些研究成果很难转化为临床实践，癌症仍然是美国死亡的主要原因。该提案旨在通过癌症基因组门户Oncomine使癌症研究人员可以轻松访问与癌症诊断，分期和预后明显相关的micro-RNA数据。如果成功，这项工作将通过为研究人员提供额外的数据和工具来了解和治疗这种生物学上复杂的疾病，从而改善公共卫生。

DESCRIPTION (provided by applicant): Micro-RNAs (miRNAs) are small non-coding RNAs that control gene expression by regulating messenger (mRNA) translation. miRNAs can act as oncogenes or tumor suppressors, and the differential expression of miRNAs has been correlated with cancer diagnosis, staging, and prognosis, and has been used to nominate therapeutic targets. Much of what is known about miRNAs in cancer comes from genome-scale miRNA expression profiling. Unfortunately, despite hundreds of published studies using miRNA profiling data, at present a basic cancer biologist lacks tools to survey the differential expression of one or more miRNAs in a specific cancer type or across the global collection of miRNA expression profiling studies. Barriers include identifying available data, platform heterogeneity, analysis methods and meaningful presentation of results. Thus, a useful solution must address a number of challenges, including the growing number of miRNAs, multiple technologies and reporters used to measure miRNA expression, disparate clinical and experimental facts, and producing biologically meaningful analyses. Here we propose to develop a solution for a biologist seeking to explore a single miRNA or a miRNA signature across the global collection of cancer miRNA data sets. To accomplish this, our overall goal is to collect all publicly available cancer-related high throughput miRNA data, to standardize the disparate data at three levels - sample data, expression data, and statistical analyses - and to present the data in a consistent, comparable format that is also fully integrated with existing, mRNA and DNA copy data in Oncomine. In Phase I we will 1) Establish and implement sample metadata curation strategy for 3 micro-RNA profiling datasets to demonstrate feasibility of applying a controlled vocabulary and ontology to miRNA sample metadata; 2) Establish and implement platform mapping strategy for 3 micro-RNA profiling datasets to demonstrate feasibility of standardizing disparate miRNA platforms into a single, unified format; 3) Perform differential expression analysis on 3 micro-RNA profiling datasets to demonstrate feasibility of creating automatically standardized analyses following the curation and mapping steps conducted in Aims 1 and 2. Upon successful completion of Phase I, we propose the following Phase II aims: 1) Development and Implementation of a scalable process for capturing and curating micro-RNA genomics data and integration into Oncomine by developing software to support the scalable catalog and capture of miRNA sample data; 2) Development of a scalable micro-RNA genomics platform mapping and data warehouse strategy and integration into Oncomine, by developing tools to accommodate dynamic naming conventions for micro-RNAS and mapping to common identifiers, and 3) Development of automated analysis methods for analyzing micro-RNA profiling datasets and integration into Oncomine by developing automated differential expression, co-expression, outlier, and meta- analysis capability across the miRNA database, and integration within the established Oncomine database. PUBLIC HEALTH RELEVANCE: Despite the substantial efforts of scientist to understand the molecular basis of cancer, these research gains have been difficult to translate into clinical practice, and cancer remains a leading cause of mortality in the United States. This proposal seeks to make micro-RNA data - which is clearly correlated with cancer diagnosis, staging, and prognosis - easily accessible to cancer researchers via the cancer genomic portal Oncomine. If successful, this effort will improve public health by providing researchers with additional data and tools to understand and treat this biologically complex disease.