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Sequence recognition

This article discusses the use of Bayesian probability for sequence recognition and trait prediction, utilizing prior and posterior probabilities. It also explores the role of genetic interactions in phenotype genetics.

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Sequence recognition

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  1. Sequence recognition (from Apr 12 ppt) Recognition question - What is the probability that the sequence s is from the start site model M ? P(M|s) = P(M)* P(s|M) / P(s) (Bayes' theorem) P(M) and P(s) are prior probabilities and P(M|s) is posterior probability.

  2. Trait prediction Probability of trait M given sequence s P(M|s) = P(M)* [P(s|M) / P(s)] Posterior = Prior * [standardized likelihood] Probability predicts unknown outcomes based on known parameters. Likelihood estimates unknown parameters based on known outcomes.

  3. Trait prediction Probability of trait M given sequence s P(M|s) = P(M)* [P(s|M) / P(s)] Monogenic: 1 = 1E-4 *[7E-2 /7E-7] “Monogenic forms of obesity at present account for approximately 7% of children with severe, young-onset obesity (3), but as this severity of obesity is only seen in <0.01% of the population .. 66% of the U.S. population had a BMI ≥ 25 kg/m2 and 32% were obese .. FTO: The 16% of adults who are homozygous for the risk allele weighed about 3 kilograms more and had a 1.67-fold increased risk of obesity” . --Frayling et al. Science 12 April 2007 FTO: 1.67*0.32 = .32 * [ .265/.16]

  4. Trait prediction given diploid s A likely scenario: Not in OMIM & heterozygous P(deleterious | s) e.g. polyphen P(dominant | s) P(epistatic | s)

  5. OMIM stats Dominant= 4170, recessive 3674 hits

  6. Genotype % chances if a subject has one copy of a (co)dominant allele "Aa" & most people are "aa". Family Risks

  7. Genotype % chances if a subject has 2 copies of a (co)dominant allele "AA" & most people are "aa". Family Risks

  8. Hardy–Weinberg equilibrium • Assumptions: • Diploid • Trait is autosomal • Is sexually reproducing, either monoecious or dioecious • Discrete generations • Random mating within a single population • Population size sufficiently large so to minimize effect of genetic drift • No selection, mutation, migration

  9. PhenotypeGeneticsallele interactions, epistasis http://galitski.systemsbiology.net//

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