The cancer genome anatomy project - Building an annotated gene index
The cancer genome anatomy project - Building an annotated gene index
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DOI：
10.1016/s0168-9525(99)01937-x
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发表时间：
2000-03-01
影响因子：
11.4
通讯作者：
Klausner, RD
中科院分区：
文献类型：
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作者：
Strausberg, RL;Buetow, KH;Klausner, RD
虽然传统的EST方法在基因编目和鉴定方面仍然非常有效，但CGAP也采用其他补充方法来提供最完整的基因目录。这些方法之一，基因表达的系列分析（SAGE），建立在整个cDNA方法的基础上，但允许从每个序列读数中识别更多数量的标签8。援助最贫穷者协商小组目前通过SAGE对基因表达进行编目的结果可在SAGEmap网站上看到（方框1）。通过与NCBI合作，为援助最贫穷者协商组开发了若干具体工具。这些工具（在方框1中进行了总结）从不同角度（基因、组织、文库、癌症与正常等）呈现数据。例如，数字差异显示工具允许个体研究人员选择所需的一组cDNA文库进行比较，并提供对基因表达的统计学显著差异的分析。该工具可用于在来自正常和癌组织的文库中搜索基因的差异表达。相比之下，“汇总表”工具从基于组织的角度提供了文库、序列和基因的目录，这些目录是从最新的UniGene构建中预先计算的。其他工具，如肿瘤抑制因子和癌基因目录提供了最新的和策划的在线信息，有关基因已知发挥作用，在癌症的发展。注释EST测序发现或揭示的基因有什么价值？基于cDNA文库和EST的表达模式分析是鉴定组织特异性基因表达的有效方法吗？一个有效的答案需要更多的实验数据，但初步证据表明，这确实是一个富有成效的方法。例如，BLAST同源性搜索鉴定了编码人端粒酶催化亚基的一部分的CGAP EST，从而能够克隆全长cDNA 9。因此，CGAP序列最初简单地注释为EST，成为克隆这一重要基因的平台。在另一种方法中，应用信息学工具，然后进行实验室实验，用于识别在人类前列腺中特异性表达的几个先前未知的基因10。最终，基因表达模式的注释需要应用有助于分析数千个基因的技术，并且这些技术非常适合分析大量组织，包括癌症发展的不同阶段。因此，CGAP基因目录的一个关键用途是微阵列的设计11。
Although the traditional EST approach continues to be very productive for cataloging and identifying genes, CGAP is also employing other complementary approaches to provide the most complete gene catalogs. One of these approaches, serial analysis of gene expression (SAGE), builds upon the overall cDNA approach, but allows the identification of a greater numbers of tags from each sequence read8. Current CGAP results in cataloging gene expression through SAGE can be seen at the SAGEmap web site (Box 1).A focus of CGAP has been to establish software tools that will enhance the use of data sets that are large and complex. Several specific tools have been developed for CGAP through a collaboration with the NCBI. These tools (summarized in Box 1) present data from various perspectives (gene, tissue, library, cancer vs normal, etc.). For example, the Digital Differential Display tool allows the individual researcher to select a desired set of cDNA libraries for comparison, and provides an analysis of statistically significant differences in gene expression. This tool can be used to search for differential expression of genes in libraries derived from normal and cancerous tissue. By contrast, the ‘Summary Tables’ tool provides catalogs of libraries, sequences and genes from a tissue based perspective, precomputed from the latest UniGene build. Other tools such as the Tumor Suppressor and Oncogene Directory provide up to date and curated on-line information about genes known to play a role in cancer development. What is the value of annotating genes discovered or revealed by EST sequencing? Is analysis of expression patterns based on cDNA libraries and ESTs an effective approach to identifying tissue-specific gene expression? An effective answer requires much more experimental data, but preliminary evidence suggests that this will indeed be a fruitful approach. For example, BLAST homology searching identified a CGAP EST encoding a portion of the human telomerase catalytic subunit, thereby enabling the cloning of the full-length cDNA9. Thus, a CGAP sequence initially annotated simply as an EST became a platform for cloning this important gene. In a different approach, application of informatics tools, followed by laboratory experimentation, were used to identify several previously unknown genes specifically expressed in human prostate10. Ultimately, the annotation of gene expression patterns requires the application of technologies that facilitate the analysis of thousands of genes, and that are well suited to analysis of large sets of tissues, including different stages of cancer development. Thus, a critical use of gene catalogs derived from CGAP is the design of microarrays11.