Incorporating microRNA data and analyses into the leading cancer genomics portal

描述(申请人提供)：microRNAs(MiRNAs)是一种小的非编码RNA，通过调节信使(MRNA)翻译来控制基因表达。MiRNAs可以作为癌基因或抑癌基因，miRNAs的差异表达与癌症的诊断、分期和预后相关，并已被用于提名治疗靶点。关于癌症中miRNAs的大部分已知信息来自于基因组规模的miRNA表达谱。不幸的是，尽管已发表了数百项使用miRNA图谱数据的研究，但目前基础癌症生物学家缺乏工具来调查一个或多个miRNAs在特定癌症类型中或跨全球miRNA表达图谱研究集合的差异表达。障碍包括确定可用的数据、平台异构性、分析方法和有意义的结果呈现。因此，一个有效的解决方案必须解决一些挑战，包括越来越多的miRNAs，用于测量miRNA表达的多种技术和报告，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数据集集合中探索单个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可公开获得的与癌症相关的高通量miRNA数据，在三个水平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复制数据完全集成。在第一阶段，我们将1)建立和实施3个microRNA图谱数据集的样本元数据精选策略，以论证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microRNA图谱数据集的平台映射策略，以论证将不同的miRNA平台标准化为单一、统一的格式的可行性；3)对3个microRNA图谱数据集进行差异表达分析，以证明遵循AIMS 1和2中进行的整理和作图步骤自动创建标准化分析的可行性。在成功完成第一阶段后，我们提出了以下第二阶段的目标：1)开发和实施可扩展的过程来捕获和整理microRNA基因组数据，并通过开发软件支持可扩展的目录和miRNA样本数据的捕获，将其整合到Oncomine中；2)开发可扩展的Micro-RNA基因组学平台作图和数据仓库策略，并通过开发工具以适应Micro-RNA的动态命名约定和映射到公共识别符，将其整合到Oncomine中；以及3)开发用于分析Micro-RNA图谱数据集的自动化分析方法，并通过在miRNA数据库中开发自动差异表达、共表达、离群值和元分析能力，以及在已建立的Oncomine数据库中进行整合，将其整合到Oncomine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。这项建议旨在使癌症研究人员通过癌症基因组门户网站Oncomine轻松获取与癌症诊断、分期和预后明显相关的Micro-RNA数据。如果成功，这项努力将通过为研究人员提供更多的数据和工具来了解和治疗这种生物上复杂的疾病，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.