Selection of optimal DNA oligos for gene expression arrays
Selection of optimal DNA oligos for gene expression arrays
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DOI：
10.1093/bioinformatics/17.11.1067
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发表时间：
2001-11-01
期刊：
影响因子：
5.8
通讯作者：
Stormo, GD
中科院分区：
文献类型：
--
作者：
Li, FG;Stormo, GD
动机：高密度DNA寡核苷酸微阵列广泛应用于生物医学研究。选择最优的DNA寡核苷酸沉积在微阵列是至关重要的。基于序列信息和杂交自由能，我们开发了一种新的算法，从基因或开放阅读框（orf）中选择最优的短（20-25个碱基）或长（50或70个碱基）寡核苷酸，并预测其杂交行为。为每个基因优化探针是有价值的，原因有二。通过最小化背景杂交，它们提供了更准确的真实表达水平测定。拥有最佳探针可以最大限度地减少每个基因所需的探针数量，从而降低每个微阵列的成本，增加每个芯片上的基因数量并增加其使用率。结果：在本文中，我们描述了算法，以优化选择特定探针的每个基因在一个完整的基因组。真正最佳探头的标准很容易表述，但目前还不能在所有级别上计算。我们已经开发了一种启发式方法，它在所有级别上都可以有效地计算，并且应该提供一个很好的近似于真正的最优集。我们已经在几个模式生物的完整基因组上运行了这个程序，并将结果存入了一个在线数据库（http://ural.wustl.edu/-lif/probe.pl）。
Motivation: High density DNA oligo microarrays are widely used in biomedical research. Selection of optimal DNA oligos that are deposited on the microarrays is critical. Based on sequence information and hybridization free energy, we developed a new algorithm to select optimal short (20-25 bases) or long (50 or 70 bases) oligos from genes or open reading frames (ORFs) and predict their hybridization behavior. Having optimized probes for each gene is valuable for two reasons. By minimizing background hybridization they provide more accurate determinations of true expression levels. Having optimum probes minimizes the number of probes needed per gene, thereby decreasing the cost of each microarray, raising the number of genes on each chip and increasing its usage.Results: In this paper we describe algorithms to optimize the selection of specific probes for each gene in an entire genome. The criteria for truly optimum probes are easily stated but they are not computable at all levels currently. We have developed an heuristic approach that is efficiently computable at all levels and should provide a good approximation to the true optimum set. We have run the program on the complete genomes for several model organisms and deposited the results in a database that is available on-line (http://ural.wustl.edu/-lif/probe.pl).