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A Practical Algorithm for Optimal Inference of Haplotypes from Diploid Populations

机译:二倍体种群的单倍型最佳推理的实用算法

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The next phase of human genomics will involve large-scale screens of populations for significant DNA polymorphisms, notably single nucleotide polymorphisms (SNP's). Dense human SNP maps are currently under construction. However, the utility of those maps and screens will be limited by the fact that humans are diploid, and that it is presently difficult to get separate data on the tow "copies". Hence genotype (blended) SNP data will be collected, and the desired haplotype (partitioned) data must then be (partially) inferred. A particular non-deterministic inference algorithm was proposed and studied before SNP data was available, and extensively applied more recently to study the first available SNP data. In this paper, we consider the question of whether we can obtain an efficient, deterministic variant of that method to optimize the obtained inferences. Although we have shown else-where that the optimization problem is NP-hard, we present here a practical approach based on (integer) linear programming. The method either returns the optimal answer, and a declaration that it is the optimal, or declares that it has failed to find the optimal. The approach works quickly and correctly, finding the optimal on all simulated data tested, data that is expected to be more demanding than realistic biological data.
机译:人类基因组学的下一阶段将涉及群体的大规模筛查,用于显着的DNA多态性,特别是单核苷酸多态性(SNP's)。密集的人体SNP地图目前正在建设中。但是,这些地图和屏幕的效用将受到人类是二倍体的事实的限制,并且目前难以在牵引“副本”上获取单独的数据。因此,将收集基因型(混合)SNP数据,然后必须(部分)推断出所需的单倍型(分区)数据。在SNP数据可用之前提出和研究了特定的非确定性推理算法,并最近广泛应用于研究第一个可用的SNP数据。在本文中,我们考虑了我们是否可以获得该方法的有效,确定性变体来优化所获得的推论的问题。虽然我们已经显示了否则 - 在那里优化问题是NP-HARD,但我们在这里展示了一种基于(整数)线性编程的实用方法。该方法要么返回最佳答案,以及它是最佳的声明,或声明它未能找到最佳状态。该方法快速且正确地运行,在所有测试数据上找到最佳数据,预期比现实的生物数据更苛刻的数据。

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