Mining complex genotypic features for predicting HIV-1 drug resistance

Hiroto Saigo, Takeaki Uno, Koji Tsuda

研究成果: Contribution to journalArticle査読

38 被引用数 (Scopus)

抄録

Motivation: Human immunodeficiency virus type 1 (HIV-1) evolves in human body, and its exposure to a drug often causes mutations that enhance the resistance against the drug. To design an effective pharmacotherapy for an individual patient, it is important to accurately predict the drug resistance based on genotype data. Notably, the resistance is not just the simple sum of the effects of all mutations. Structural biological studies suggest that the association of mutations is crucial: even if mutations A or B alone do not affect the resistance, a significant change might happen when the two mutations occur together. Linear regression methods cannot take the associations into account, while decision tree methods can reveal only limited associations. Kernel methods and neural networks implicitly use all possible associations for prediction, but cannot select salient associations explicitly. Results: Our method, itemset boosting, performs linear regression in the complete space of power sets of mutations. It implements a forward feature selection procedure where, in each iteration, one mutation combination is found by an efficient branch-and-bound search. This method uses all possible combinations, and salient associations are explicitly shown. In experiments, our method worked particularly well for predicting the resistance of nucleotide reverse transcriptase inhibitors (NRTIs). Furthermore, it successfully recovered many mutation associations known in biological literature.

本文言語英語
ページ(範囲)2455-2462
ページ数8
ジャーナルBioinformatics
23
18
DOI
出版ステータス出版済み - 9 15 2007
外部発表はい

All Science Journal Classification (ASJC) codes

  • 統計学および確率
  • 生化学
  • 分子生物学
  • コンピュータ サイエンスの応用
  • 計算理論と計算数学
  • 計算数学

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