论文标题

在DNA阵列杂交实验中选择控制克隆的算法方法

Algorithmic approaches to selecting control clones in DNA array hybridization experiments

论文作者

Fu, Qi, Bent, Elizabeth, Borneman, James, Chrobak, Marek, Young, Neal E.

论文摘要

我们研究了在DNA阵列杂交实验中选择控制克隆的问题。这个问题是在分析微生物群落的OFRG方法中。 OFRG方法使用由一系列杂交实验创建的二进制指纹对rRNA基因克隆进行分类,其中每个实验包括将阵列克隆的集合与单个寡核苷酸探针杂交。该实验会产生模拟信号,每个克隆一个,然后需要分类,即转换为代表杂交和非杂交事件的二进制值1和0。除了样品rRNA基因克隆外,阵列还包含校准杂交信号的分类过程所需的许多控制克隆。必须小心选择这些控制克隆以优化分类过程。我们将其作为一个称为平衡覆盖的组合优化问题。我们证明了问题是NP-hard,并且我们对近似硬度显示了一些结果。我们提出了基于随机舍入的近似算法,我们表明,算法较高的算法近似最佳解决方案。实验结果证实了算法找到高质量控制克隆。该算法已实施,并作为称为Clonetools的软件包的一部分公开使用。

We study the problem of selecting control clones in DNA array hybridization experiments. The problem arises in the OFRG method for analyzing microbial communities. The OFRG method performs classification of rRNA gene clones using binary fingerprints created from a series of hybridization experiments, where each experiment consists of hybridizing a collection of arrayed clones with a single oligonucleotide probe. This experiment produces analog signals, one for each clone, which then need to be classified, that is, converted into binary values 1 and 0 that represent hybridization and non-hybridization events. In addition to the sample rRNA gene clones, the array contains a number of control clones needed to calibrate the classification procedure of the hybridization signals. These control clones must be selected with care to optimize the classification process. We formulate this as a combinatorial optimization problem called Balanced Covering. We prove that the problem is NP-hard, and we show some results on hardness of approximation. We propose approximation algorithms based on randomized rounding and we show that, with high probability, our algorithms approximate well the optimum solution. The experimental results confirm that the algorithms find high quality control clones. The algorithms have been implemented and are publicly available as part of the software package called CloneTools.

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