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1038 0
2011-09-21

Hidden Markov models have been successfully applied to a variety of

problems in molecular biology, ranging from alignment problems to gene finding and

annotation. let us consider a problem of finding CpG-islands in the human genome. Since

there is relative high chance that methyl-C will mutate to T except at the CpG-islands in the

promoter regions of genes, we’ll see more CpG-pairs in the CpG-islands than elsewhere.

Therefore, CpG-islands are useful markers for genes in human and some other organisms.

The question is that how to determine a segment of genome sequence from a CpG-island. For

instance, consider a DNA sequence of AGCGCGATC. Apply a HMM model that assumes a

transition probability matrix for the two states, CpG-island denoted by + and Non CpG-island

denoted by as below:

                         right

Probability       +         −

            +       0.8       0.2

  Left

            −       0.9       0.1

The emission probability matrix is assumed to be:

Probability     A         C         G         T

      +         0.20     0.35     0.26     0.19

      −         0.35     0.15     0.10     0.40

These probabilities are made up here. In practice, they can be estimated through learning from

training data of the known genes. Calculate the probability of observing a DNA sequence of

AGCGCGATC under a probable state path + + + + + − − − for the model assumed. What

is that probability under the path + + + + + − − − −?
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