| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
We have previously proposed an algorithm, distance-based sequential-linking method, for longitudinal analysis of within-host viral evolution and successfully reconstructed a longitudinal phylogenetic tree of 24 HIV-1 env gene sequences obtained from patients who had not received drug treatment. However, viral evolution in patients who are undergoing drug therapy, especially HARRT (Highly Active Anti-Retroviral Therapy), is much more complicated because of the selective pressure from the anti-viral drugs. To estimate this complicated process, we largely improved the previous algorithm by introducing information criterion into our method. We employed C4.5 (software package, Quinlan, 1993), which is developed based on mutual information criterion, to obtain the decision tree that identifies the relations between virus samples and drug combinations administered. We applied the revised algorithm to a large data set (189 sequences) of HIV-1 protease gene serially sampled from a single patient under HAART over three years. The obtained decision tree showed that there were always two or more viral subpopulations with different frequencies and also different characteristic mutations during the whole observation period. Moreover, by estimating the synonymous (ds) and nonsynonymous (d_N) substitution rates of each viral subpopulation classified by the decision tree, we found that the selective pressure exerted on the virus is highly variable over time when different drugs are administered, but the virus may often be under positive Darwinian selection to evolve.
The above results have been presented at several meetings including international meetings (SMBE2004, ISMB2004), and received the "Excellent Theme Prize" from the 18th annual meeting of the Japanese society for AIDS research
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