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Turning quantity into quality: novel quality assurance strategies for data produced by high-throughput genomics technologies 将数量转化为质量:高通量基因组技术产生的数据的新型质量保证策略
Pub Date : 2002-10-01 DOI: 10.1016/S1477-3627(02)02207-9
Hans Peter Fischer

The pharmaceutical industry is facing the challenge of managing the exponential increase in volume, diversity and complexity of data generated by high-throughput technologies such as genome sequencing, gene-expression profiling, protein-expression profiling, metabolic profiling and high-throughput screening. These novel ‘genomics’ technologies are expected to reshape the approach of life science companies to research. Unfortunately, in many cases genomics technologies have been used uncritically, and some preliminary results have been disappointing. The lack of standardized data validation and quality assurance processes is recognized as one of the major hurdles for successfully implementing genomics technologies. This is particularly important for industrialized drug discovery processes, because more and more key conclusions and far-reaching decisions in the pharmaceutical industry are based on data that is generated automatically. Therefore, automated, specialized quality-control systems that can spot erroneous data that might obscure important biological effects are needed urgently. In this article, special emphasis is placed on DNA microarray technologies, a key genomics technology that suffers from severe problems with data quality. A generic, automatable data-quality-assurance workflow is discussed that will ultimately improve the quality of the drug candidates and, at the same time, reduce overall drug-development costs.

制药行业正面临着管理高通量技术(如基因组测序、基因表达谱、蛋白质表达谱、代谢谱和高通量筛选)产生的数据数量、多样性和复杂性呈指数级增长的挑战。这些新颖的“基因组学”技术有望重塑生命科学公司的研究方法。不幸的是,在许多情况下,基因组技术被不加批判地使用,一些初步结果令人失望。缺乏标准化的数据验证和质量保证过程被认为是成功实施基因组学技术的主要障碍之一。这对于工业化药物发现过程尤其重要,因为制药工业中越来越多的关键结论和影响深远的决定是基于自动生成的数据。因此,迫切需要能够发现可能掩盖重要生物效应的错误数据的自动化、专业化的质量控制系统。在本文中,特别强调了DNA微阵列技术,这是一项关键的基因组学技术,受到严重的数据质量问题的困扰。本文讨论了一种通用的、可自动化的数据质量保证工作流程,它将最终提高候选药物的质量,同时降低总体药物开发成本。
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引用次数: 4
Finding the molecules to fuel chemogenomics 寻找分子来推动化学基因组学
Pub Date : 2002-10-01 DOI: 10.1016/S1477-3627(02)02206-7
Mark N. Namchuk

Within the pharmaceutical industry, chemogenomics focuses on obtaining maximum benefit from the small molecules created in the drug-discovery process. Part of this discipline is the application of small-molecule inhibitors to aid in the characterization of the biological function of targets. The wider application of these approaches is hampered by a lack of reagents – that is, small molecules that have been thoroughly characterized and have appropriate potency and specificity for the target of interest. This review focuses on approaches used in the pharmaceutical industry to produce compounds for use in chemogenomics and on the challenges encountered in quickly characterizing their effects on biological activity.

在制药行业,化学基因组学侧重于从药物发现过程中产生的小分子中获得最大利益。本学科的一部分是应用小分子抑制剂来帮助表征靶标的生物学功能。这些方法的广泛应用受到试剂缺乏的阻碍,试剂是指已经被彻底表征并对感兴趣的目标具有适当效力和特异性的小分子。这篇综述的重点是制药工业中用于化学基因组学的化合物的生产方法,以及在快速表征其对生物活性的影响方面遇到的挑战。
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引用次数: 5
About drugs and airplanes: will better use of data and information pave the road to success? 关于药物和飞机:更好地利用数据和信息会为成功铺平道路吗?
Pub Date : 2002-10-01 DOI: 10.1016/S1477-3627(02)02211-0
Jack Elands
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引用次数: 0
Shimadzu scientist awarded Nobel Prize for Chemistry 岛津科学家获诺贝尔化学奖
Pub Date : 2002-10-01 DOI: 10.1016/S1477-3627(02)02229-8
Tetsuo Ichikawa
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引用次数: 0
First genome study of anticarcinogen bears fruit 抗癌物质的首次基因组研究取得成果
Pub Date : 2002-10-01 DOI: 10.1016/S1477-3627(02)02210-9
Apoorva Mandavilli
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引用次数: 0
Using mouse forward genetics to define novel target space 利用小鼠前向遗传学定义新的目标空间
Pub Date : 2002-10-01 DOI: 10.1016/S1477-3627(02)02208-0
Nancy A. Hong, Steve A. Kay, Richard J. Glynne

Rapid advances in genomics technologies have identified a wealth of new therapeutic targets, but typically these targets are weakly validated with only circumstantial evidence to link them to human disease. The next challenge is testing gene-to-disease connections in a relevant animal model, a time-consuming and uncertain process using conventional reverse-genetic approaches such as knockout and transgenic mice. By contrast, forward genetics proceeds by measuring a physiological process that is relevant to disease, then identifying the gene products that impinge on this process. This ‘phenotype-first’ approach solves the bottleneck of target validation by using clinically relevant assays in a mammalian whole-animal system as a discovery platform. As an unbiased approach to gene discovery and validation, forward genetics will identify novel drug targets and increase the success rate of drug development.

基因组学技术的快速发展已经确定了大量新的治疗靶点,但通常这些靶点的有效性很弱,只有间接证据将它们与人类疾病联系起来。下一个挑战是在相关的动物模型中测试基因与疾病的联系,这是一个耗时且不确定的过程,使用传统的反遗传方法,如基因敲除和转基因小鼠。相比之下,正向遗传学通过测量与疾病相关的生理过程,然后识别影响这一过程的基因产物来进行。这种“表型优先”的方法通过在哺乳动物全动物系统中使用临床相关分析作为发现平台,解决了靶标验证的瓶颈。作为一种公正的基因发现和验证方法,正向遗传学将识别新的药物靶点,提高药物开发的成功率。
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引用次数: 1
Genzyme optimizes the universe 健赞优化宇宙
Pub Date : 2002-10-01 DOI: 10.1016/S1477-3627(02)02219-5
Martina Habeck (freelance writer)
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引用次数: 0
Iceland's genome fits another piece in schizophrenia puzzle 冰岛的基因组解开了精神分裂症之谜的另一块拼图
Pub Date : 2002-09-01 DOI: 10.1016/S1477-3627(02)02201-8
Katharine Pestell
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引用次数: 0
News in brief 新闻简讯
Pub Date : 2002-09-01 DOI: 10.1016/S1477-3627(02)02238-9
Joanne Clough, Linsey Stapley, Heather Yeomans
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引用次数: 0
Aromatase and COX-2 in the anti-cancer loop 芳香化酶和COX-2在抗癌循环中的作用
Pub Date : 2002-09-01 DOI: 10.1016/S1477-3627(02)02202-X
Paul Thacker (freelance writer)
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引用次数: 1
期刊
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