alexa Inference of missing SNPs and information quantity measurements for haplotype blocks.
Genetics

Genetics

Molecular Biology: Open Access

Author(s): Su SC, Kuo CC, Chen T, Su SC, Kuo CC, Chen T

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Abstract MOTIVATION: Missing data in genotyping single nucleotide polymorphism (SNP) spots are common. High-throughput genotyping methods usually have a high rate of missing data. For example, the published human chromosome 21 data by Patil et al. contains about 20\% missing SNPs. Inferring missing SNPs using the haplotype block structure is promising but difficult because the haplotype block boundaries are not well defined. Here we propose a global algorithm to overcome this difficulty. RESULTS: First, we propose to use entropy as a measure of haplotype diversity. We show that the entropy measure combined with a dynamic programming algorithm produces better haplotype block partitions than other measures. Second, based on the entropy measure, we propose a two-step iterative partition-inference algorithm for the inference of missing SNPs. At the first step, we apply the dynamic programming algorithm to partition haplotypes into blocks. At the second step, we use an iterative process similar to the expectation-maximization algorithm to infer missing SNPs in each haplotype block so as to minimize the block entropy. The algorithm iterates these two steps until the total block entropy is minimized. We test our algorithm in several experimental data sets. The results show that the global approach significantly improves the accuracy of the inference. AVAILABILITY: Upon request. This article was published in Bioinformatics and referenced in Molecular Biology: Open Access

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