Computational biology of regulation by small RNAs

小RNA调控的计算生物学

• 批准号: 7342135
• 负责人: CHRIS SANDER
• 金额: $ 36.34万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7342135
• 关键词: Algorithms; Area; Biological; Biological Process; Body of uterus; Cellular biology; Chromatin; Classification; Complement; Computational Biology; Computer software; Computing Methodologies; Data; Databases; Detection; Development; Disease; Foundations; Functional RNA; Gene Proteins; Gene Silencing; Gene Targeting; Genetic Transcription; Genetic Variation; Immune system; Information Networks; Information Resources; Investigation; Laboratories; Mammalian Cell; Mammals; Modeling; Modification; Molecular; Non-Insulin-Dependent Diabetes Mellitus; Numbers; Pathway interactions; Process; Production; Proteins; Public Domains; RNA Splicing; Rate; Reaction; Regulation; Research; Resources; Small RNA; Structure; Transcript; Transcriptional Regulation; Translational Repression; Translations; Validation; Work; base; clinical application; design; genome sequencing; novel; programs; research study; tool

Gene silencing and other regulatory processes guided by small RNAs are important additions to the known repertoire of biological control mechanisms. Both the total number and biological function of small RNA gene products are still largely unknown, especially in mammals. It is plausible, based on recent experiments and predictions, that there are many more non-coding RNAs than have been discovered to date and that these may be involved in regulating transcription, splicing, translation, and chromatin modification. Discovery of the complement of small RNAs, their biological functions and disease implications is therefore an important aim in molecular cell biology. Our overall aim is to help unravel the molecular details of regulatory control by small RNAs, with focus on mammals, and to develop tools for the prediction of the functional effects of this control. We will use computational means, including algorithms, software, databases and complete genome sequences, working closely with the experimental laboratories of our collaborators. We will start with the systematic and broad experimental capture of small RNA profiles and the detection and validation of target genes of small RNAs. We then plan to put small RNAs and their regulatory targets into the context of known pathways, providing a rich unified network information resource. Using this resource we will (i) analyze and predict the consequences of changes in small RNAs, their control regions and their targets, (ii) facilitate the design of focussed validation experiments and (iii) lay the foundations for the development of clinical applications. Specific areas of investigation will be the immune system and type 2 diabetes. During the course of this research, we will construct detailed regulatory networks of small RNAs and associated biological effects including: transcriptional control of small RNA production, gene silencing by translational inhibition or degradation of transcripts, and chromatin modification. We propose to organize and analyze this information in the context of the growing corpus of structured pathway data for genes, proteins, interactions and reactions in mammalian cells. For each of the specific aims we will facilitate dissemination and application of the results of the program project by making available in the public domain both software and information resources. Specific Aims: a) Profiles: Build a data annotation pipeline for small RNA profiling of mammalian cells, b) Targets: Develop computational methods for the identification and validation of the functional targets of small RNAs. c) Networks: Construct regulatory networks involving small RNAs, d) Function: Analyze the function of small RNAs and the consequences of genetic variation.

由小RNA引导的基因沉默和其他调控过程是对已知生物控制机制的重要补充。小RNA基因产物的总数和生物学功能在很大程度上仍然未知，特别是在哺乳动物中。根据最近的实验和预测，有可能存在比迄今为止发现的更多的非编码RNA，并且这些RNA可能参与调节细胞的生长。 转录、剪接、翻译和染色质修饰。因此，发现小RNA的补体、它们的生物学功能和疾病意义是分子细胞生物学的重要目标。我们的总体目标是帮助解开小RNA调控的分子细节，重点是哺乳动物，并开发预测这种控制的功能效应的工具。我们将使用计算手段，包括算法，软件，数据库和完整的基因组序列，与我们合作者的实验室密切合作。我们将从系统和广泛的小RNA谱的实验捕获以及小RNA靶基因的检测和验证开始。然后，我们计划将小RNA及其调控靶点置于已知通路的背景下，提供丰富的统一网络信息资源。利用这些资源，我们将（i）分析 并预测小RNA、其控制区和其靶点变化的后果，（ii）促进重点验证实验的设计，（iii）为临床应用的发展奠定基础。研究的具体领域将是免疫系统和2型糖尿病。在本研究的过程中，我们将构建详细的小RNA调控网络和相关的生物学效应，包括：转录控制的小RNA生产，基因沉默的翻译抑制或降解的转录本，和染色质修饰。我们建议组织和分析这些信息的背景下，不断增长的语料库的结构化途径数据的基因，蛋白质，在哺乳动物细胞中的相互作用和反应。对于每一个具体目标，我们将通过在公共领域提供软件和信息资源来促进计划项目成果的传播和应用。 具体目标： a）概况：构建用于哺乳动物细胞的小RNA谱分析的数据注释管道。B）靶标：开发用于鉴定和验证小RNA的功能靶标的计算方法。c）网络：构建涉及小RNA的调控网络，d）功能：分析小RNA的功能和遗传变异的后果。