Developing Software For Protein-Based Gene Finding

开发基于蛋白质的基因查找软件

• 批准号: 7122546
• 负责人: Morgan Corinne GIDDINGS
• 金额: $ 40.23万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-16 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7122546
• 关键词: bioengineering /biomedical engineering; bioinformatics; biotechnology; computational biology; computer program /software; computer system design /evaluation; functional /structural genomics; genetic mapping; human genetic material tag; mass spectrometry; proteomics

DESCRIPTION (provided by applicant): The first human genome sequencing efforts are complete, which has opened the door to many new and challenging questions. Among these are the quantity and location of genes in the genome, both of which have proven surprisingly difficult to pinpoint. Even further from a definitive answer is the question of how many distinct functional RNA and protein products are produced by each gene through mechanisms such as alternative splicing. These unanswered questions impede a full understanding of the genome and how it functions in relation to human disease. We are proposing innovative software technology that has the potential to help overcome this obstacle, using mass spectrometry measurements of proteins to reveal the location and structure of the genes encoding those proteins within the genome. This technology can be applied to help answer several critical questions. For example, where are all the genes located in the genome? What are their exon-intron structures? How many distinct products do they encode? We propose to modify and combine the already proven software programs TWINSCAN and GFS, that were developed by our labs for genomic and proteomic purposes, respectively, to address these new challenges in genome analysis. TWINSCAN is a highly accurate, automated gene finder, and GFS is a proteomics tool that matches mass spectrometry (MS) peptide data from enzymatically digested proteins direcdy to raw (even unfinished) genome sequence, identifying the coding loci for the proteins. Here, we propose a two-pronged approach to produce a novel, protein-based method for finding genes and determining their structure. Our aims comprise the following: a) extending GFS for automated use with multi-exon genes und very large genomes, to facilitate discovery of novel genes and gene structures; b) modifying TWINSCAN to use peptide data from GFS to enhance its rapid, automated gene finding capabilities; c) combining the two programs into an automated protein-based gene finder, and d) validating the approach for gene-finding using synthetic and experimental data sets.

描述（由申请人提供）：第一个人类基因组测序工作已经完成，这为许多新且具有挑战性的问题打开了大门。其中包括基因在基因组中的数量和位置，这两者都被证明很难确定。从确定的答案中，甚至还有一个问题，即每个基因通过替代剪接等机制产生了多少不同的功能性RNA和蛋白质产物。这些未解决的问题阻碍了人们对基因组及其与人类疾病有关的功能的全面理解。我们提出了创新的软件技术，该技术有可能帮助克服这一障碍，使用质谱测量蛋白质来揭示编码基因组中这些蛋白质的基因的位置和结构。该技术可用于帮助回答几个关键问题。例如，所有基因都位于基因组中的哪里？他们的外显子内结构是什么？它们编码多少个不同的产品？ 我们建议修改和组合已经经过验证的软件程序Twinscan和GFS，这些程序是由我们的实验室开发的，分别用于基因组和蛋白质组学目的，以应对基因组分析中的这些新挑战。 Twinscan是一种高度准确的自动基因发现器，GFS是一种蛋白质组学工具，可匹配质谱（MS）肽数据，从酶消化的蛋白质直接到原始（甚至未完成的）基因组序列，从而识别蛋白质的编码位点。在这里，我们提出了一种两种普通的方法，以产生一种基于蛋白质的新方法来查找基因并确定其结构。我们的目标包括以下内容：a）扩展GFS用于自动使用的多exon基因和非常大的基因组，以促进发现新型基因和基因结构； b）修改双胞胎以使用来自GFS的肽数据来增强其快速自动化的基因发现能力； c）将两个程序组合到基于蛋白质的基因发现器中，d）使用合成和实验数据集验证基因调查的方法。