INCREASED SENSITIVITY OF COMPUTER ANALYSES OF LARGE GENOMES

随着大量原核生物和真核生物的迅速出现 基因组序列，重要的是评估能力和 当前计算机方法在生物解释中的局限性 这些序列，并扩展这些方法以允许更大范围的 待识别的功能特征。序列的详细分析 酵母染色体III和部分大肠杆菌染色体正在进行 作为测试用例执行，以便定义一组适当的方法。 -gt；来自酵母染色体III序列(315kb)，182 最初报告的开放阅读框(ORF)，以及其他 完全包含在这些ORF内或基因间的ORF 区域，受到基于BLAST算法的策略的影响 与序列数据库的比较。极低的爆炸得分阈值是 最初定义的和所有可能被怀疑是 使用多重比对对生物学意义进行了详细评估 方法：研究方法。这一分析导致了有意义的相似之处的识别 与其他31个开放阅读框架的蛋白质结合，除了所描述的29个 和37个已知基因，因此提高到50%以上 其功能分配和/或序列的ORF的一部分 关系是可以利用的。发现了显著的序列相似性 在一个基因间区只有一个额外的ORF，这表明基因 松散地堆积在这个酵母染色体上。此外，使用 识别跨膜片段的策略，49种可能 发现了17种膜蛋白，其中17种含有多个可能的 跨膜螺旋，可作为转运体或受体发挥作用。 统计方法也在应用，以评估 ORF和其他各种属性的任何集群的意义 DNA序列特征。 该项目的意义在于其发展潜力。 改进的基因功能和基因功能计算机分析策略 大基因组中的基因排列和DNA特征。

With the rapid appearance of large portions of prokaryotic and eukaryotic genome sequences, it is important to assess the capabilities and limitations of current computer methods for biological interpretation of these sequences, and to extend the methods to allow a greater range of functional features to be identified. Detailed analyses of sequences of yeast chromosome III and portions of the E. coli chromosome are being performed as test cases in order to define an adequate set of methods. >From the yeast chromosome III sequence (315 kilobases), 182 initially-reported open reading frames (ORFs), together with additional ORFs that were completely contained within these ORFs or in intergene regions, were subjected to a strategy based on the BLAST algorithm for comparison with sequence databases. Very low BLAST score thresholds were initially defined and every similarity that could be suspected to be biologically significant was assessed in detail using multiple alignment methods. This analysis led to identification of meaningful similarities with other proteins for 31 ORFs, in addition to the 29 described previously and the 37 known genes, thus raising to over 50 percent the fraction of ORFs for which functional assignment and/or sequence relationships were available. Significant sequence similarity was found for only one additional ORF in an intergene region, suggesting that genes are loosely packed in this yeast chromosome. In addition, using strategies for identification of transmembrane segments, 49 possible membrane proteins were found, of which 17 contained multiple probable transmembrane helices and may function as transporters or receptors. Statistical methods are also being applied in order to assess the significance of any clustering of various attributes of ORFs and other DNA sequence features. The significance of the project lies in the potential for development of improved strategies for computer analysis of gene functions and arrangement of genes and DNA features in large genomes.