Rich Probabilistic Models for Genomic Data基因组数据的丰富的概率模型.pptVIP

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Rich Probabilistic Models for Genomic Data基因组数据的丰富的概率模型.ppt

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Rich Probabilistic Models for Genomic Data基因组数据的丰富的概率模型

* Phasing by EM Frequencies 0 0 0 1 0 1/6 0 0 0 1 1 0 1 0 0 0 1 0 1 0 0 1 0 0 1 0 0 1 1 1/2 1 0 1 0 1 1/6 1 0 1 1 1 0 1 1 0 1 1 0 1 1 1 1 1 1/6 Haplotypes Data:1 0 h h 1 h 0 0 1 h 1 h h 1 1 1 0 0 0 1 1 0 1 1 1 1 0 0 1 1 1 0 1 0 1 0 0 0 1 0 1 0 0 1 1 0 0 0 1 1 1 0 0 1 0 1 0 0 1 1 1 1 1 1 1 1 0 1 1 1 1 1 0 1 1 ? ? ? ? ? ? ? ? ? ? ? ? 0 1 1 0 1 0 * Computational Cost (for SNPs) Consider sets of m unphased genotypes Markers 1..m If markers are bi-allelic 2m possible haplotypes 2m-1 (2m + 1) possible haplotype pairs 3m distinct observed genotypes 2n-1 reconstructions for n heterozygous loci For example, if m = 10 For example, if m=10 = 1024 = 524,800 = 59,049 = 512 * EM Algorithm For Haplotyping Cost grows rapidly with number of markers Typically appropriate for 25 SNPs Fewer microsatellites More accurate than Clark’s method Fully or partially phased individuals contribute most of the information Enhancements to EM List only haplotypes present in sample Gradually expand subset of markers under consideration, eliminating haplotypes with low estimated frequency from consideration at each stage SNPHAP, Clayton (2001) HAPLOTYPER, Qin et al (2002) * * Divide-And-Conquer Approximation Number of potential haplotypes increases exponentially Number of observed haplotypes does not Approximation Successively divide marker set Locally phase each segment through EM Prune haplotype list as segments are ligated Merge by phasing vectors of haplotype pairs Computation order: ~ m log m Exact EM is order ~ 2m 1 0 0 1 0 1 00 0 0 1 1 0 1 0 1 0 1 1 0 01 1 1 0 0 1 1 1 0 0 0 0 0 00 1 1 1 1 1 0 * Many of the techniques we will be discussing in class are based on the probabilistic models. Examples include Bayesian networks, Hidden markov models or Markov Random Fields. So, today, before we start discussing computational methods in active areas of research, we’d like to spend a couple of lectures for some basics on probabilistic models. Lectures 6