Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
PLoS One. 2009 Sep 4;4(9):e6907. doi: 10.1371/journal.pone.0006907.
Personalized, or genomic, medicine entails tailoring pharmacological therapies according to individual genetic variation at genomic loci encoding proteins in drug-response pathways. It has been previously shown that steady-state mRNA expression can be used to predict the drug response (i.e., sensitivity or resistance) of non-genotyped mammalian cancer cell lines to chemotherapeutic agents. In a real-world setting, clinicians would have access to both steady-state expression levels of patient tissue(s) and a patient's genotypic profile, and yet the predictive power of transcripts versus markers is not well understood. We have previously shown that a collection of genotyped and expression-profiled yeast strains can provide a model for personalized medicine. Here we compare the predictive power of 6,229 steady-state mRNA transcript levels and 2,894 genotyped markers using a pattern recognition algorithm. We were able to predict with over 70% accuracy the drug sensitivity of 104 individual genotyped yeast strains derived from a cross between a laboratory strain and a wild isolate. We observe that, independently of drug mechanism of action, both transcripts and markers can accurately predict drug response. Marker-based prediction is usually more accurate than transcript-based prediction, likely reflecting the genetic determination of gene expression in this cross.
个性化或基因组医学需要根据编码药物反应途径中蛋白质的基因组基因座的个体遗传变异来定制药物治疗。先前已经表明，稳态 mRNA 表达可用于预测非基因分型哺乳动物癌细胞系对化疗药物的药物反应（即敏感性或耐药性）。在现实环境中，临床医生将能够获得患者组织的稳态表达水平和患者的基因型谱，但转录物与标志物的预测能力尚不清楚。我们之前已经表明，一组基因分型和表达谱酵母菌株可以为个性化医学提供模型。在这里，我们使用模式识别算法比较了 6229 个稳态 mRNA 转录本水平和 2894 个基因分型标记的预测能力。我们能够以超过 70%的准确度预测来自实验室菌株和野生分离株杂交的 104 个个体基因分型酵母菌株的药物敏感性。我们观察到，独立于药物作用机制，转录本和标志物都可以准确预测药物反应。基于标记的预测通常比基于转录本的预测更准确，这可能反映了这种杂交中基因表达的遗传决定。
