DNA与错配模板杂交的芯片研究
DNA hybridization to mismatched templates: a chip study
摘要：
高密度寡核苷酸阵列是当今生物学中发展最快的技术之一。在{ \sl GeneChip}系统中，靶浓度的重建取决于靶RNA与两个几乎相同的模板杂交产生的差异信号：完全匹配（PM）和单个错配（MM）探针。已经观察到，与序列特异性杂交的通常预期相反，大部分MM探针比PM更好地可重复地结合靶标;这在基础物理学方面难以解释。我们研究这个问题，通过一个大的微阵列实验的统计分析。我们分类的探头根据其信号噪声（$S/N$）比，定义为（PM，MM）对的“轨迹”在许多实验的偏心率。在那些具有大的$S/N$（$>3$）的探针中，只有一部分的行为与通常假定的杂交模型一致。我们的研究结果意味着，微阵列中的DNA杂交的物理比预期的更复杂，他们提出了新的方法来构建估计的目标RNA浓度。
英文摘要：
High-density oligonucleotide arrays are among the most rapidly expanding technologies in biology today. In the {\sl GeneChip} system, the reconstruction of the target concentration depends upon the differential signal generated from hybridizing the target RNA to two nearly identical templates: a perfect match (PM) and a single mismatch (MM) probe. It has been observed that a large fraction of MM probes repeatably bind targets better than the PMs, against the usual expectation from sequence-specific hybridization; this is difficult to interpret in terms of the underlying physics. We examine this problem via a statistical analysis of a large set of microarray experiments. We classify the probes according to their signal to noise ($S/N$) ratio, defined as the eccentricity of a (PM, MM) pair's `trajectory' across many experiments. Of those probes having large $S/N$ ($>3$) only a fraction behave consistently with the commonly assumed hybridization model. Our results imply that the physics of DNA hybridization in microarrays is more complex than expected, and they suggest new ways of constructing estimators for the target RNA concentration.
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