Problem statement from Dr. Camps

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Mutation Rates in HIV Genomes
Dr. Manel Camps
We have used the Stanford drug HIV database to identify mutations
in the reverse transcriptase and protease sequences of the HIV virus
occurring in individual infected patients. Using this approach we
found a subset of viral genomes that appear to evolve much faster
than the rest (10-100-fold higher mutation frequency than average).
The goal of this project is to determine whether the observed
increased frequency in this subset of viral genomes is due to
increased generation of mutations or instead to increased positive
selection.
Specifically, to discriminate between these two alternatives we will
look at:
1. Distribution of mutations along sequence (localized vs. spread-out
2. Concordance between different patients
3. Ratio of non-synonymous to synonymous mutations
If the increased mutation rate is due to positive selection, mutations
will be used to identify sites of rapid evolution as candidates for
interaction with the patient’s Immune system.
If, by contrast, the observed increased rate is due to increased
generation of mutations, mutations will be used to map areas of the
virus that have relaxed evolutionary constraints.
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