Whole transcriptome analysis for neurobiology

神经生物学的全转录组分析

• 批准号: 8515535
• 负责人: Jonathan Buckley
• 金额: $ 43.35万
• 依托单位: EPICENTER SOFTWARE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8515535
• 关键词: Analysis of Variance; Atlases; Attention; Base Sequence; Bioinformatics; Biological; Biological Neural Networks; Brain; Cell physiology; Clinical; Clinical Research; Complex; Computer software; CpG Islands; DNA Methylation; Data; Data Analyses; Data Set; Databases; Development; Discipline; Disease; Elements; Ensure; Evaluation; Exons; Factor Analysis; Functional RNA; Gene Expression Profile; Genes; Genome; Genomics; Glioblastoma; Human; Imagery; Individual; Informatics; Internet; Introns; Junk DNA; Link; Location; Measurement; Measures; Methods; Methylation; MicroRNAs; Modeling; Names; Nervous system structure; Neurobiology; Neuroblastoma; Neurologic; Non-linear Models; Organ; Pattern; Phase; Principal Component Analysis; Process; Proteins; RNA; RNA Editing; RNA Splicing; Regression Analysis; Regulation; Research; Sampling; Schizophrenia; Scientist; Signaling Protein; Site; Software Tools; Technology; Time; Tissues; Trans-Splicing; Transcript; Transcriptional Regulation; Variant; base; biological research; data management; data reduction; design; digital; empowered; epigenomics; histone modification; new technology; next generation; programs; relating to nervous system; screening; software development; tool; transcription factor

DESCRIPTION (provided by applicant): Development of an organ as complex as the brain depends on an intricate interplay of thousands of signaling proteins, orchestrated by an interacting web of regulatory factors. Recent ENCODE data reveal that the large tracts of so-called 'junk' DNA in introns and between genes is, in fact, actively transcribed. The functions of these non-coding transcripts, which number in the millions, are virtually unknown, although one small sib-class - the microRNAs - is receiving close attention as regulatory RNAs. One process that may be controlled by the non-coding transcripts is alternate exon use - a mechanism that adds significantly to the diversity of cellular proteins (particularly in the CNS), the regulation of which is little understood at this time. Recent advances that generate whole-transcriptome data have provided the means to systematically explore both these factors. However, the bioinformatic challenges are substantial, and the lack of comprehensive, well designed, and easily used software to manage, visualize, analyze and interpret the data will likely be the limiting factor in this field of research. We propose to develop a bioinformatics toolkit specifically to integrate whole-transcriptome data from two different technologies, the Affymetrix All Exon microarray which 1.4 million distinct transcript measurements, and RNASeq, which provides for 'digital' expression analysis of the whole transcriptome. The toolkit will also integrate epigenomic data that will be essential in the understanding of regulation of transcription. The design and development of the software will be guided by prominent scientists engaged in the study of the brain, and will be applied to sample datasets derived from neurological tissues, to ensure that the program incorporates functions and annotations relevant to this field.

描述(申请人提供)：像大脑一样复杂的器官的发展依赖于数千种信号蛋白质的复杂相互作用，这些蛋白质由一个相互作用的调节因子网络协调。最近的ENCODE数据显示，事实上，内含子内和基因之间的大片所谓的“垃圾”DNA被活跃地转录。这些数以百万计的非编码转录本的功能几乎是未知的，尽管有一个小的同胞类-microRNAs-作为调节RNAs正受到密切关注。一个可能由非编码转录本控制的过程是交替外显子使用--这是一种显著增加细胞蛋白质多样性的机制(特别是在中枢神经系统中)，目前对其调控尚不清楚。产生完整转录组数据的最新进展为系统地探索这两个因素提供了手段。然而，生物信息学的挑战是巨大的，缺乏全面的、精心设计的、易于使用的软件来管理、可视化、分析和解释数据，这可能是这一研究领域的限制因素。我们建议开发一个生物信息学工具包，专门用于集成来自两种不同技术的整个转录组数据，Affymetrix All Exon微阵列包括140万个不同的转录组测量，以及RNAseq，它提供对整个转录组的‘数字’表达分析。该工具包还将整合对理解转录调控至关重要的表观基因组数据。该软件的设计和开发将由从事大脑研究的知名科学家指导，并将应用于来自神经组织的样本数据集，以确保该程序包含与该领域相关的功能和注释。