用聚类法分析受抗真菌物质处理后的酵母细胞全基因表达谱

微阵列DNA芯片技术可以并行分析成千上万个基因的表达情况，它为研究药物的作用机制提供了一个新的高效技术平台.用9种已知和未知作用机理的抗真菌化合物处理酵母细胞，并得到酵母细胞的全基因表达谱，然后对其进行聚类分析.结果表明作用机制类似的化合物具有相近的聚类关系.两性霉素B和制霉菌素、酮康唑和克霉唑都是已知的作用机制类似的抗真菌药物.通过对基因表达谱进行聚类分析，发现前一组和后一组分别被聚类在一起.另外已知澳洲茄胺抑制的是细胞膜上麦角固醇的合成，聚类分析表明它与酮康唑，克霉唑的聚类很靠近.对微阵列DNA芯片产生的基因表达谱进行聚类分析，由于作用机制相似的药物会被聚类在一起，因此根据未知药物和已知药物的聚类关系，可以了解未知药物的作用机制，这对于加速新药开发的步伐具有十分重要的意义.

Cluster Analysis of Yeast Genome-wide Expression Patterns Obtained by Treating With Different Antifungal Agents

To examine the application of DNA microarray in drug discovery and development, cluster analysis for genome-wide expression data was tested after Saccharomyces cerevisiae was treated with nine antifungal agents with known and unknown pharmacological mechanisms. The results indicated that antifungal agents with similar action mode were clustered together. Amphotericin B and nystatin, ketoconazole and clotrimazole have been known to have similar antifungal mechanism respectively. Consistent with their known mechanisms, amphotericin B and nystatin were clustered together; also ketoconazole and clotrimazole were clustered together based on their expression patterns. Solasodine, which was known to inhibit the synthesis of ergosterol, had a close clustering position with ketoconazole and clotrimazole group. Analyzing the relationship among the known and unknown drugs using cluster approach, It can be infered that the pharmacological mechanisms of unknown drugs from their clustering positions relating to the known drugs.