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arXiv 1202.2468math.PRcs.DM
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谱系隐马尔可夫模型的最优状态空间约简

Optimal State-Space Reduction for Pedigree Hidden Markov Models

Bonnie Kirkpatrick, Kay Kirkpatrick

摘要:

为了分析家族中遗传的全基因组遗传数据,通常从具有2 ^n个隐藏状态的状态空间的隐马尔可夫模型(HMM)获得似然性,其中n是谱系中减数分裂或边缘的数量。已经有几种尝试通过减少HMM的状态空间来加速该计算。这些方法中的一种已经在比朴素HMM计算更有效的计算中自动化;然而,该方法处理特殊情况,并且效率增益仅适用于那些包含长链独生子谱系的罕见谱系。另一种现有的状态空间约简方法处理的是一般情况,但现有的算法具有超指数的运行时间。我们提出了三个配方的状态空间减少问题,两个处理组和分区之一。其中最大等距群问题由Browning和Browning详细讨论过。我们表明,谱系,所有这三个问题有相同的解决方案。此外,我们能够证明的唯一性的解决方案,使用我们介绍的算法。该算法利用划分和组公式之间的等价性,快速找到一般谱系的最佳状态空间约简。我们提出了一个新的似然计算,这是一个两阶段的过程:找到最佳的状态空间,然后运行HMM的前向-后向算法的最佳状态空间。与单阶段HMM计算相比,该方法可以更快地计算出精确的谱系似然。

英文摘要:

To analyze whole-genome genetic data inherited in families, the likelihood is typically obtained from a Hidden Markov Model (HMM) having a state space of 2^n hidden states where n is the number of meioses or edges in the pedigree. There have been several attempts to speed up this calculation by reducing the state-space of the HMM. One of these methods has been automated in a calculation that is more efficient than the naive HMM calculation; however, that method treats a special case and the efficiency gain is available for only those rare pedigrees containing long chains of single-child lineages. The other existing state-space reduction method treats the general case, but the existing algorithm has super-exponential running time. We present three formulations of the state-space reduction problem, two dealing with groups and one with partitions. One of these problems, the maximum isometry group problem was discussed in detail by Browning and Browning. We show that for pedigrees, all three of these problems have identical solutions. Furthermore, we are able to prove the uniqueness of the solution using the algorithm that we introduce. This algorithm leverages the insight provided by the equivalence between the partition and group formulations of the problem to quickly find the optimal state-space reduction for general pedigrees. We propose a new likelihood calculation which is a two-stage process: find the optimal state-space, then run the HMM forward-backward algorithm on the optimal state-space. In comparison with the one-stage HMM calculation, this new method more quickly calculates the exact pedigree likelihood.

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