Yamada Tomoyuki, Soma Haruhiko, Morishita Shinichi
Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan.
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W665-9. doi: 10.1093/nar/gkl297.
PrimerStation (http://ps.cb.k.u-tokyo.ac.jp) is a web service that calculates primer sets guaranteeing high specificity against the entire human genome. To achieve high accuracy, we used the hybridization ratio of primers in liquid solution. Calculating the status of sequence hybridization in terms of the stringent hybridization ratio is computationally costly, and no web service checks the entire human genome and returns a highly specific primer set calculated using a precise physicochemical model. To shorten the response time, we precomputed candidates for specific primers using a massively parallel computer with 100 CPUs (SunFire 15 K) about 3 months in advance. This enables PrimerStation to search and output qualified primers interactively. PrimerStation can select highly specific primers suitable for multiplex PCR by seeking a wider temperature range that minimizes the possibility of cross-reaction. It also allows users to add heuristic rules to the primer design, e.g. the exclusion of single nucleotide polymorphisms (SNPs) in primers, the avoidance of poly(A) and CA-repeats in the PCR products, and the elimination of defective primers using the secondary structure prediction. We performed several tests to verify the PCR amplification of randomly selected primers for ChrX, and we confirmed that the primers amplify specific PCR products perfectly.
引物站(http://ps.cb.k.u-tokyo.ac.jp)是一项网络服务,可计算出能保证对整个人类基因组具有高特异性的引物组。为实现高精度,我们使用了引物在液体溶液中的杂交率。根据严格的杂交率计算序列杂交状态在计算上成本很高,而且没有网络服务会检查整个人类基因组并返回使用精确物理化学模型计算出的高特异性引物组。为缩短响应时间,我们大约提前3个月使用具有100个CPU的大规模并行计算机(SunFire 15 K)预先计算特异性引物的候选序列。这使得引物站能够交互式地搜索并输出合格的引物。引物站可以通过寻找更宽的温度范围来选择适合多重PCR的高特异性引物,从而将交叉反应的可能性降至最低。它还允许用户在引物设计中添加启发式规则,例如排除引物中的单核苷酸多态性(SNP)、避免PCR产物中出现聚腺苷酸(poly(A))和CA重复序列,以及使用二级结构预测消除有缺陷的引物。我们进行了多项测试以验证随机选择的针对X染色体的引物的PCR扩增情况,并且我们确认这些引物能完美地扩增出特异性PCR产物。