Lee Jungsul, Park Junseong, Choi Chulhee
Department of Bio and Brain Engineering, KAIST, Daejeon, 305-701, Republic of Korea.
1] Department of Bio and Brain Engineering, KAIST, Daejeon, 305-701, Republic of Korea [2] KAIST Institute for the BioCentury, Daejeon, 305-701, Republic of Korea.
Sci Rep. 2014 Mar 19;4:4413. doi: 10.1038/srep04413.
Systemic identification of deterministic genes for different phenotypes is a primary application of high-throughput expression profiles. However, gene expression differences cannot be used when the differences between groups are not significant. Therefore, novel methods incorporating features other than expression differences are required. We developed a promising method using transcriptional response as an operational feature, which is quantified as the correlation between expression levels of pathway genes and target genes of the pathway. We applied this method to identify causative genes associated with chemo-sensitivity to tamoxifen and epirubicin. Genes whose transcriptional response was dysregulated only in the drug-resistant patient group were chosen for in vitro validation in human breast cancer cells. Finally, we discovered two genes responsible for tamoxifen sensitivity and three genes associated with epirubicin sensitivity. The method we propose here can be widely applied to identify deterministic genes for different phenotypes with only minor differences in gene expression levels.
系统鉴定不同表型的决定性基因是高通量表达谱的主要应用。然而，当组间差异不显著时，基因表达差异就无法使用。因此，需要结合表达差异以外特征的新方法。我们开发了一种有前景的方法，将转录反应作为操作特征，其被量化为通路基因表达水平与该通路靶基因之间的相关性。我们应用此方法来鉴定与对他莫昔芬和表柔比星化疗敏感性相关的致病基因。仅在耐药患者组中转录反应失调的基因被选择用于人乳腺癌细胞的体外验证。最后，我们发现了两个负责他莫昔芬敏感性的基因和三个与表柔比星敏感性相关的基因。我们在此提出的方法可广泛应用于鉴定基因表达水平仅有微小差异的不同表型的决定性基因。
