NIH Chemical Genomics Center

在2005年开始科学运作后，国家地质公园在报告所述年度达到了人员配备和生产的满负荷状态。 该中心目前与全球100多名研究人员合作，在这一年中对几乎所有生物学和疾病领域（包括癌症、心脏病、传染病和神经系统疾病）重要的分子靶点和细胞表型进行了50多次高通量筛选。 在这一年中，NCGC全面实施了其基于滴定的定量高通量筛选（qHTS）模式，并证明它比传统方法显着提高了筛选效率。 NCGC信息学部门建立了一个全新的基础设施，以处理和从qHTS产生的大量数据中提取自动化结论（通常在一个实验中产生200 - 500万个数据点），并准备出版和传播这些程序。 同样在这一年，国家药物管制中心化学司达到了全员编制，使丰富的筛选和信息学数据能够用于药物化学优化活动，以开发和发布各种新的化学探针。 其中包括一组新的戈谢病（Gaucher Disease，一种人类溶酶体贮积病，发表于PNAS 104：13192-7）、阿尔茨海默病（Alzheimer Disease，发表于Neurobiology of Disease doi：10.1016/j.nbd.2007.07.018）和血吸虫病（已出版）的分子伴侣。 总的来说，生产指标包括筛选的> 18，000，000种化合物，生成的> 2，250，000个浓度-反应曲线，生成的> 2.33亿个数据点，以及存储到PubChem中的> 21，000，000个数据字段。 NCGC在这一年中扩大了其已经广泛的推广计划，以教育学术界关于化学基因组学方法和能力，并协助研究人员进行分析开发工作。 NCGC的工作人员在这一年里在世界各地举办了60多场特邀讲座，从纽约和洛杉矶到日本、德国和西班牙。 为了进一步扩大其教育范围，NCGC测定开发手册在NCGC网站（www.ncgc.nih.gov）上进行了更新并达到4.1版，NCGC在Nature Chemical Biology（3：466-79）中发表了HTS测定开发的全面综述。

After beginning scientific operations in 2005, the NCGC reached full staffing and production during the reporting year. The Center is now working with over 100 researchers worldwide, and during the year performed over 50 high-throughput screens on molecular targets and cellular phenotypes important for virtually every area of biology and disease, including cancer, heart disease, infectious diseases, and neurological disorders. During this year, the NCGC fully operationalized its titration-based Quantitative High Throughput Screening (qHTS) paradigm, and demonstrated that it significantly improves the efficiency of screening over conventional methods. The NCGC Informatics Division built an entirely new infrastructure to process and extract automated conclusions from the vast amount of data qHTS produces (routinely producing 2-5 million data points in a single experiment), and is preparing those programs for publication and dissemination. Also during the year, the NCGCs Chemistry Division reached full staffing, allowing the rich screening and informatics data to be used in medicinal chemistry optimization campaigns to develop and publish a variety of new chemical probes. Among these were a group of new chaperone leads for Gaucher Disease, a human lysosomal storage disease (published in PNAS 104:13192-7), Alzheimer Diease (published in Neurobiology of Disease doi:10.1016/j.nbd.2007.07.018), and Schistosomiasis (publication in press). In all, production metrics included >18,000,000 compounds screened, >2,250,000 concentration-response profiles generated, >233 million data points generated, and >21,000,000 data fields deposited into PubChem. The NCGC expanded its already-extensive outreach program during the year, in order to both educate the academic community about chemical genomics methods and capabilities, and assist researchers in their assay development efforts. NCGC staff delivered over 60 invited lectures worldwide during the year, from New York and Los Angeles to Japan, Germany, and Spain. In order to extend its educational reach further, the NCGC Assay Development Manual was updated and reached version 4.1 on the NCGC website (www.ncgc.nih.gov), and the NCGC published a comprehensive review of assay development for HTS in Nature Chemical Biology (3:466-79).