A new pooling strategy for high-throughput screening: the Shifted Transversal Design.
A new pooling strategy for high-throughput screening: the Shifted Transversal Design.
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DOI：
10.1186/1471-2105-7-28
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发表时间：
2006-01-19
影响因子：
3
通讯作者：
Thierry-Mieg, N
中科院分区：
文献类型：
--
作者：
Thierry-Mieg, N
在二元高通量筛选项目中，目标是识别低频事件，除了明显的效率问题外，误报和漏报也是一个主要问题。合并构成了一种自然的解决方案：它减少了测试数量，同时提供了各个实验的关键重复，从而纠正了实验噪声。主要困难在于以高效且稳健的方式设计池：需要很少的池来纠正错误和识别阳性，但实验不应该太容易受到生物不稳定的影响。例如，即使阳性或错误比预期稍多，仍然应该获得一些信息。这称为组测试问题或池问题。在本文中，我们提出了一种新的非自适应组合池设计：“移位横向设计”（STD）。它依赖于算术，并基于两个直观的想法：最小化对象的共现，以及构建恒定大小的交集池。我们证明它允许对嘈杂的实验观察结果进行明确的解码。这种设计非常灵活，可以定制以在各种实验设置（即对象数量、阳性分数和预期错误率）中稳健运行。此外，我们表明，就效率而言，我们的设计与之前描述的非自适应组合池设计相比具有优势。目前，该方法正在与达纳法伯癌症研究所的 Marc Vidal 实验室合作，通过在酵母-双杂交相互作用组图谱背景下的现场测试进行验证。许多类似的项目可以从使用移动横向设计中受益。
In binary high-throughput screening projects where the goal is the identification of low-frequency events, beyond the obvious issue of efficiency, false positives and false negatives are a major concern. Pooling constitutes a natural solution: it reduces the number of tests, while providing critical duplication of the individual experiments, thereby correcting for experimental noise. The main difficulty consists in designing the pools in a manner that is both efficient and robust: few pools should be necessary to correct the errors and identify the positives, yet the experiment should not be too vulnerable to biological shakiness. For example, some information should still be obtained even if there are slightly more positives or errors than expected. This is known as the group testing problem, or pooling problem. In this paper, we present a new non-adaptive combinatorial pooling design: the "shifted transversal design" (STD). It relies on arithmetics, and rests on two intuitive ideas: minimizing the co-occurrence of objects, and constructing pools of constant-sized intersections. We prove that it allows unambiguous decoding of noisy experimental observations. This design is highly flexible, and can be tailored to function robustly in a wide range of experimental settings (i.e., numbers of objects, fractions of positives, and expected error-rates). Furthermore, we show that our design compares favorably, in terms of efficiency, to the previously described non-adaptive combinatorial pooling designs. This method is currently being validated by field-testing in the context of yeast-two-hybrid interactome mapping, in collaboration with Marc Vidal's lab at the Dana Farber Cancer Institute. Many similar projects could benefit from using the Shifted Transversal Design.
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