Incorporating microRNA data and analyses into the leading cancer genomics portal

描述（由申请人提供）：微rna （miRNAs）是一种小的非编码rna，通过调节信使（mRNA）的翻译来控制基因表达。miRNAs可以作为癌基因或肿瘤抑制因子，miRNAs的差异表达与癌症的诊断、分期和预后相关，并已被用于指定治疗靶点。我们对癌症中miRNA的了解大多来自基因组尺度的miRNA表达谱。不幸的是，尽管已经发表了数百篇使用miRNA分析数据的研究，但目前基础癌症生物学家缺乏工具来调查一种或多种miRNA在特定癌症类型或全球miRNA表达分析研究中的差异表达。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一系列挑战，包括不断增长的miRNA数量，用于测量miRNA表达的多种技术和报告器，不同的临床和实验事实，以及产生具有生物学意义的分析。在这里，我们建议为寻求在全球癌症miRNA数据集中探索单个miRNA或miRNA签名的生物学家开发一种解决方案。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与癌症相关的高通量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——并以一致的、可比较的格式呈现数据，该格式也与Oncomine中现有的mRNA和DNA拷贝数据完全集成。在第一阶段，我们将1)建立并实施3个微rna分析数据集的样本元数据管理策略，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)建立并实施3个微rna分析数据集的平台制图策略，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分析数据集进行差异表达分析，以证明按照目标1和目标2中进行的策展和制图步骤创建自动标准化分析的可行性。在成功完成第一阶段后，我们提出以下第二阶段目标：1)开发和实施可扩展的流程，用于捕获和管理微rna基因组学数据，并通过开发软件来支持可扩展的miRNA样本数据目录和捕获，将其集成到Oncomine中；2)开发可扩展的微rna基因组学平台映射和数据仓库策略，并集成到Oncomine中，通过开发工具来适应微rna的动态命名约定和映射到公共标识符。3)开发用于分析微rna分析数据集的自动化分析方法，并通过开发跨miRNA数据库的自动差异表达、共表达、异常值和元分析能力集成到Oncomine中。并在已建立的Oncomine数据库内进行整合。

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.