Statistical & Computational Methods For Gene Expression

统计

• 批准号: 6988060
• 负责人: peter j munson
• 金额: --
• 依托单位: CENTER FOR INFORMATION TECHNOLOGY
• 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/6988060
• 关键词: bioinformatics; computer program /software; computer system design /evaluation; gene expression; human subject; microarray technology; molecular biology information system; oligonucleotides; proteomics; statistics /biometry

Gene expression measurement using cDNA and oligo arrays is exploding in popularity, yet many technical problems remain. In parallel, high throughput methods for measuring protein concentrations are being developed. One of the more challenging problems results from the large volume of data generated in these experiments. Image capture, processing, interpretation and quantification remain as important fundamental issues. Quality control and experimental design must be carefully addressed. Numerous statistical, image processing and bioinformatics issues remain problematic. Accordingly, these projects seek to address such problems. In a major NIH-wide project, we maintain a database for storage, retrieval and analysis of Affymetrix oligo-based microarrays, NIHLIMS. As part of this collaboration, we are creating a data analysis pipeline and bioinformatics toolset, including both commercial and freely available software. The database currently stores information from over 2000 microarrays. Our web-based analysis (A-SCAN) and downloadable tool set (MSCL Analyst's Toolbox) are now mature, widely tested and applied in numerous studies. Working with laboratories in NCI, CC, NHLBI, NINDS, NIAID, NHGRI, NICHD, NIA, NIDDK, NIDA we have developed, customized and applied software for the analysis of microarray based studies. In one of several major studies with the Critical Care Medicine Department, CC, we have designed and analyzed a study of the genomics of recovery and subsequent rejection of heart transplants in a novel animal model. The goal is to identify markers of rejection which could eventually be used in monitoring recovery from transplant in humans. We have developed a novel statistical tool, GO-SCAN for analysis of gene annotations associated with differentially expressed genes. The tool provides several compact visualizations of annotation space, and has been successfully applied in the analysis of an endotoxin response study in which over 1,000 differentially expressed genes were identified. A web-version of the tool is now also available. In an ongoing study of pineal function with investigators of NICHD, we identified several hundred genes which manifest circadien variation in rats, and for which measurement of homologs in human and monkey were feasible. Interestingly, pineal function in primates appears to be controlled in a very different way from rodents. In one of two proteomics initiatives, we collaborated with investigators in CCMD to apply mass-spectroscopy for identification of novel entities as possible markers of infection in BAL (bronchial alveolar lavage) fluid. A time course study of normal volunteers exposed to endotoxin demonstrated a significant number of varying spectroscopic peaks, which were subsequently identified molecularly. A study of samples from ARDS (acute respiratory distress syndrome) patients confirmed most of these results. Methods previously developed by this lab for reverse-phase proteomic arrays were applied in studies undertaken by investigators of Laboratory of Molecular Pharmacology, NCI. MSCL staff participated in a nationwide collaboration to advance sepsis research, a topic of high interest to critical care medicine. A major invited lecture was presented at the 2nd Symposium on Functional Genomics of Critical Illness and Injury. The MSCL staff frequently provides advice and guidance to several Institutes and Laboratories as they apply new microarray , proteomic and bioinformatics techniques. In particular, NHLBI, NICHD, NINDS, NIDA and NIDDK have requested and received extensive consultations in this area. MSCL staff also participate in the NIH-wide Biomedical Information Science and Technology Initiative (BISTI) Consortium serve as the focus of biomedical computing issues at the NIH

使用cDNA和寡核苷酸阵列的基因表达测量正在普及，但仍存在许多技术问题。与此同时，正在开发用于测量蛋白质浓度的高通量方法。其中一个更具挑战性的问题来自这些实验中产生的大量数据。图像采集、处理、解释和量化仍然是重要的基本问题。质量控制和实验设计必须仔细处理。许多统计、图像处理和生物信息学问题仍然存在。因此，这些项目力求解决这些问题。 在NIH范围内的一个主要项目中，我们维护了一个数据库，用于存储、检索和分析基于Affyphyrin寡核苷酸的微阵列，NIHLIMS。作为合作的一部分，我们正在创建一个数据分析管道和生物信息学工具集，包括商业和免费软件。该数据库目前存储来自2000多个微阵列的信息。我们基于网络的分析（A-SCAN）和可下载的工具集（MSCL Analyst's Toolkit）现已成熟，并在众多研究中得到广泛测试和应用。与NCI，CC，NHLBI，NINDS，NIAID，NHGRI，NICHD，NIA，NIDDK，NIDA的实验室合作，我们开发，定制和应用软件用于基于微阵列的研究分析。 在重症监护医学部的几项主要研究之一中，CC，我们设计并分析了一项新动物模型中心脏移植恢复和随后排斥反应的基因组学研究。目标是确定排斥反应的标志物，这些标志物最终可用于监测人类移植后的恢复。 我们已经开发了一种新的统计工具，GO-SCAN分析与差异表达基因相关的基因注释。该工具提供了注释空间的几个紧凑的可视化，并已成功应用于内毒素反应研究的分析，其中鉴定了1,000多个差异表达的基因。该工具的网络版现已推出。 在NICHD的研究人员正在进行的松果体功能的研究中，我们确定了几百个基因，这些基因在大鼠中表现出昼夜节律的变化，并且在人类和猴子中测量同源物是可行的。有趣的是，灵长类动物的松果体功能似乎以一种与啮齿类动物非常不同的方式控制。 在两项蛋白质组学研究中，我们与CCMD的研究人员合作，应用质谱法鉴定新实体作为BAL（支气管肺泡灌洗）液中感染的可能标志物。对暴露于内毒素的正常志愿者进行的时程研究显示了大量不同的光谱峰，随后在分子水平上进行了鉴定。对ARDS（急性呼吸窘迫综合征）患者样本的研究证实了大部分这些结果。 本实验室以前开发的反相蛋白质组阵列方法应用于NCI分子药理学实验室研究人员进行的研究。 MSC L工作人员参与了一项全国性的合作，以推进脓毒症研究，这是重症监护医学高度感兴趣的话题。在第二届危重疾病和损伤的功能基因组学研讨会上发表了一个重要的特邀演讲。 MSCL的工作人员经常提供建议和指导，几个研究所和实验室，因为他们应用新的微阵列，蛋白质组学和生物信息学技术。特别是，NHLBI、NICHD、NINDS、NIDA和NIDDK要求并得到了这方面的广泛协商。MSCL工作人员还参加了NIH范围内的生物医学信息科学与技术倡议（BISTI）联盟，该联盟是NIH生物医学计算问题的焦点