Specialized Tools and Auto-updatable Scalable Interactive Databases to Study isomiRs, tRFs and rRFs in Human and Mouse

用于研究人类和小鼠 isomiR、tRF 和 rRF 的专用工具和可自动更新、可扩展的交互式数据库

基本信息

批准号：
10736401
负责人：
Isidore Rigoutsos
金额：
$ 55.31万
依托单位：
THOMAS JEFFERSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-02 至 2027-05-31
项目状态：
未结题

项目摘要

This project focuses on three categories of small RNAs: the isoforms of microRNAs (miRNAs) that are known as isomiRs; the fragments that are derived from transfer RNAs (tRNAs) and are known as tRFs; and, the frag- ments that are derived from ribosomal RNAs (rRNAs) and are known as rRFs. IsomiR, tRFs, and rRFs have several important properties that warrant their detailed study: (1) They account for ~80% of all small RNAs in a cell. (2) They regulate the abundance of messenger RNAs (mRNAs) and pro- teins. (3) Their expression patterns depend on cellular “context” (e.g., tissue type, disease type). (4) In hu- mans, their expression patterns additionally depend on “personal attributes” (e.g., sex, genetic ancestry, age). To correctly mine isomiRs, tRFs, and rRFs from RNA-seq data the ideal tools must address several compli- cating factors. First, the same short sequence (e.g., tRF) can arise from different parental RNAs. These parental RNAs can belong to the same sub-type (e.g., different tRNA isodecoders of the same tRNA isoacceptor) or different sub-types (e.g., isodecoders from different tRNA isoacceptors). Second, the sequences of many iso- miRs, tRFs, and rRFs can also be found in unrelated regions of the genome. Third, paralogues and/or incomplete copies of miRNAs, tRNAs, and rRNAs riddle the nuclear genomes of many organisms including human and mouse. The details of these complicating factors are specific to the RNA type and to the genome. Consequently, the ideal tools must be target-genome-specific. The complicating factors and the need for genome specificity appeared in the literature only recently. As a result, most available tools to date have been general-purpose and do not account for these complications. Not surprisingly, most available databases were built using general-purpose tools. Without realizing the underlying shortcomings, many researchers relied on the information provided by these tools and databases to design experiments and analyze their data. In turn, this has led to many published articles that unintentionally describe findings of unclear value about molecules that are not always isomiRs, tRFs, or rRFs. We will address these gaps as follows. In Aim 1, we will build specialized tools that address the peculiarities of each RNA type and accurately mine isomiRs, tRFs, and rRFs from human and mouse RNA-seq data. The tools will be robust, self-contained, and user-friendly. In Aim 2, we will build specialized databases to organize and provide easy access to information about isomiRs, tRFs, and rRFs that we have already compiled by mining 50,000 public datasets. In Aim 3, we will build a system that auto-identifies newly-added datasets to NIH’s SRA, profiles and annotates each dataset’s isomiRs, tRFs, and rRFs, and updates the databases with the new infor- mation each month. In Aim 4, we will create educational material describing best practices to help researchers benefit maximally from this framework, and build a system to allow them to interact with one another and submit their feedback. Lastly, we will validate experimentally select small RNAs implicated in breast cancer metastasis.

该项目重点关注三类小 RNA：已知的 microRNA (miRNA) 亚型作为 isomiR；源自转移 RNA (tRNA) 的片段，称为 tRF；衍生自核糖体 RNA (rRNA) 的物质被称为 rRF。 IsomiR、tRF 和 rRF 具有几个值得进行详细研究的重要特性：(1) 它们解释了细胞中约 80% 的小 RNA (2) 它们调节信使 RNA (mRNA) 和 pro- 的丰度。 (3) 它们的表达模式取决于细胞“环境”（例如组织类型、疾病类型）。 (4) 在人类中。对于男性来说，他们的表达模式还取决于“个人属性”（例如性别、遗传血统、年龄）。为了从 RNA-seq 数据中正确挖掘 isomiR、tRF 和 rRF，理想的工具必须解决几个复杂的问题：首先，相同的短序列（例如，tRF）可以来自不同的亲本RNA。 RNA 可以属于相同的亚型（例如，同一 tRNA 同工受体的不同 tRNA 同工解码器）或不同的亚型（例如，来自不同 tRNA 同工受体的同工编码器）其次，许多异工的序列。 miR、tRF 和 rRF 也可以在基因组的不相关区域中找到。第三，旁系同源物和/或不完整区域。 miRNA、tRNA 和 rRNA 的拷贝困扰着许多生物体的核基因组，包括人类和这些复杂因素的细节特定于 RNA 类型和测试的基因组。理想的工具必须是特定于目标基因组的。复杂的因素和对基因组特异性的需求最近才出现在文献中。结果，迄今为止大多数可用的工具都是通用的，并没有考虑到这些复杂性。令人惊讶的是，大多数可用的数据库都是使用通用工具构建的，而没有意识到底层的情况。缺点，许多研究人员依靠这些工具和数据库提供的信息来设计反过来，这导致了许多无意中描述的文章的发表。关于并不总是 isomiR、tRF 或 rRF 的分子价值不明确的发现。我们将按如下方式解决这些差距，在目标 1 中，我们将构建专门的工具来解决这些问题。每种 RNA 类型的数据，并从人类和小鼠 RNA-seq 数据中准确挖掘 isomiR、tRF 和 rRF。工具将是强大的、独立的、用户友好的。在目标 2 中，我们将建立专门的数据库来组织。并提供对我们已经通过挖掘编译的 isomiRs、tRFs 和 rRFs 的信息的轻松访问在目标 3 中，我们将构建一个自动识别 NIH SRA 新增数据集的系统，50,000 个公共数据集。配置文件并注释每个数据集的 isomiR、tRF 和 rRF，并使用新信息更新数据库在目标 4 中，我们将创建描述最佳实践的教育材料以帮助研究人员。最大限度地从这个框架中受益，并建立一个系统，让他们能够相互交互并提交最后，我们将通过实验验证选择的与乳腺癌转移有关的小RNA。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

MINRbase: a comprehensive database of nuclear- and mitochondrial-ribosomal-RNA-derived fragments (rRFs).

MINRbase：核和线粒体核糖体 RNA 衍生片段 (rRF) 的综合数据库。

DOI：
发表时间：
2024-01-05
期刊：
影响因子：
14.9
作者：
Pliatsika, Venetia;Cherlin, Tess;Loher, Phillipe;Vlantis, Panagiotis;Nagarkar, Parth;Nersisyan, Stepan;Rigoutsos, Isidore
通讯作者：
Rigoutsos, Isidore