Physico-chemical modelling of target depletion during hybridization on oligonulceotide microarrays
Physico-chemical modelling of target depletion during hybridization on oligonulceotide microarrays
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DOI：
10.1088/1478-3975/7/1/016004
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发表时间：
2010-03-01
期刊：
影响因子：
2
通讯作者：
Binder, Hans
中科院分区：
文献类型：
--
作者：
Burden, Conrad J.;Binder, Hans
从上清液中去除靶分子的效果被纳入寡核苷酸微阵列上杂交的物理化学模型中。确定了两种可能的制度：本地耗尽，其中由一个给定的探针功能耗尽只影响该特定的探针，和全球耗尽，其中响应于一个给定的目标物种的所有功能受到影响。给出了两个现有的尖峰在数据集的目标耗尽经历可测量的影响的例子。其中第一个，来自Suzuki等人使用具有宽范围探针长度和错配位置的定制阵列的实验，被验证为表现出局部而非全局耗尽。第二个数据集，著名的Affyoung HGU133a拉丁方实验，被证明是很好地解释了全球耗尽模型。结果表明，依赖于朗缪尔等温线模型，忽略耗尽效应的微阵列校准将显着低估特定的目标浓度。它还表明，完美的匹配和不匹配的探针信号在一个简单的图形总结，即钩状曲线法的组合分析，可以区分的情况下，本地和全球耗尽。
The effect of target molecule depletion from the supernatant solution is incorporated into a physico-chemical model of hybridization on oligonucleotide microarrays. Two possible regimes are identified: local depletion, in which depletion by a given probe feature only affects that particular probe, and global depletion, in which all features responding to a given target species are affected. Examples are given of two existing spike-in data sets experiencing measurable effects of target depletion. The first of these, from an experiment by Suzuki et al using custom built arrays with a broad range of probe lengths and mismatch positions, is verified to exhibit local and not global depletion. The second data set, the well-known Affymetrix HGU133a latin square experiment, is shown to be very well explained by a global depletion model. It is shown that microarray calibrations relying on Langmuir isotherm models which ignore depletion effects will significantly underestimate specific target concentrations. It is also shown that a combined analysis of perfect match and mismatch probe signals in terms of a simple graphical summary, namely the hook curve method, can discriminate between cases of local and global depletion.