Rosenfeld Simon
National Cancer Institute, EPN 3108, 6130 Executive Blvd., Rockville, Maryland 20892.
Gene Regul Syst Bio. 2010 Jun 29;4:61-73. doi: 10.4137/grsb.s4657.
Poor reproducibility of microarray measurements is a major obstacle to their application as an instrument for clinical diagnostics. In this paper, several aspects of poor reproducibility are analyzed. All of them belong to the category of interpretive weaknesses of DNA microarray technology. First, the attention is drawn to the fact that absence of the information regarding post-transcriptional mRNA stability makes it impossible to evaluate the level of gene activity from the relative mRNA abundances, the quantities available from microarray measurements. Second, irreducible intracellular variability with persistent patterns of stochasticity and burstiness put natural limits to reproducibility. Third, strong interactions within intracellular biomolecular networks make it highly problematic to build a bridge between transcription rates of individual genes and structural fidelity of their genetic codes. For these reasons, the microarray measurements of relative mRNA abundances are more appropriate in laboratory settings as a tool for scientific research, hypotheses generating and producing the leads for subsequent validation through more sophisticated technologies. As to clinical settings, where firm conclusive diagnoses, not the leads for further experimentation, are required, microarrays still have a long way to go until they become a reliable instrument in patient-related decision making.
微阵列测量结果的可重复性差是其作为临床诊断工具应用的主要障碍。本文分析了可重复性差的几个方面。所有这些都属于DNA微阵列技术解释性弱点的范畴。首先，需要注意的是，由于缺乏转录后mRNA稳定性的信息，无法从相对mRNA丰度（微阵列测量可获得的量）来评估基因活性水平。其次，细胞内不可减少的变异性以及持续的随机性和突发性模式给可重复性设定了自然限制。第三，细胞内生物分子网络中的强相互作用使得在单个基因的转录速率与其遗传密码的结构保真度之间建立联系变得非常困难。由于这些原因，相对mRNA丰度的微阵列测量在实验室环境中更适合作为科学研究、生成假设以及通过更复杂技术产生后续验证线索的工具。至于临床环境，在那里需要的是确切的确定性诊断，而不是进一步实验的线索，微阵列在成为患者相关决策中可靠工具之前仍有很长的路要走。
