Using the nucleotide substitution rate matrix to detect horizontal gene transfer.
Using the nucleotide substitution rate matrix to detect horizontal gene transfer.
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DOI：
10.1186/1471-2105-7-476
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发表时间：
2006-10-26
影响因子：
3
通讯作者：
Knight R
中科院分区：
文献类型：
--
作者：
Hamady M;Betterton MD;Knight R
水平基因转移（HGT）使细菌进化出许多新的能力。由于转移的基因执行许多医学上重要的功能，例如赋予抗生素抗性，因此从序列数据中改进水平转移基因的检测将是一个重要的进步。现有的基于序列的HGT检测方法集中在核苷酸组成的变化或基因和基因组同源性之间的差异，这些方法具有高错误率。首先，我们介绍了一类新的方法来检测HGT的基础上发生的变化时，一个基因被转移到一个新的生物体的核苷酸取代率。我们的新方法区分模拟HGT事件的错误率比GC含量低10倍。使用时间不可逆的模型对于检测HGT至关重要。其次，我们表明，使用HGT的多个预测因子的组合提供了实质性的改进，使用任何单一的预测因子，产生多达18的性能改善的因素（错误率从38%最大降低到约3%）。通过使用随机森林机器学习算法来组合多个预测器，以识别将HGT与非HGT树分开的最佳分类器。这里介绍的一类新的HGT检测方法结合了系统发育和组成HGT检测技术的优势。这些新技术提供了数量级的改进，因为它们能够更好地区分HGT从非HGT树在广泛的模拟条件下的组合方法。我们还发现，结合多种措施的HGT是必不可少的检测范围广泛的HGT事件。这些水平转移的新指标将广泛用于检测与重要细菌性状（如抗生素抗性和致病性）进化相关的HGT事件。
Horizontal gene transfer (HGT) has allowed bacteria to evolve many new capabilities. Because transferred genes perform many medically important functions, such as conferring antibiotic resistance, improved detection of horizontally transferred genes from sequence data would be an important advance. Existing sequence-based methods for detecting HGT focus on changes in nucleotide composition or on differences between gene and genome phylogenies; these methods have high error rates. First, we introduce a new class of methods for detecting HGT based on the changes in nucleotide substitution rates that occur when a gene is transferred to a new organism. Our new methods discriminate simulated HGT events with an error rate up to 10 times lower than does GC content. Use of models that are not time-reversible is crucial for detecting HGT. Second, we show that using combinations of multiple predictors of HGT offers substantial improvements over using any single predictor, yielding as much as a factor of 18 improvement in performance (a maximum reduction in error rate from 38% to about 3%). Multiple predictors were combined by using the random forests machine learning algorithm to identify optimal classifiers that separate HGT from non-HGT trees. The new class of HGT-detection methods introduced here combines advantages of phylogenetic and compositional HGT-detection techniques. These new techniques offer order-of-magnitude improvements over compositional methods because they are better able to discriminate HGT from non-HGT trees under a wide range of simulated conditions. We also found that combining multiple measures of HGT is essential for detecting a wide range of HGT events. These novel indicators of horizontal transfer will be widely useful in detecting HGT events linked to the evolution of important bacterial traits, such as antibiotic resistance and pathogenicity.
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影响因子：
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作者：
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DOI：
10.1073/pnas.90.3.1033
发表时间：
1993-02-01
影响因子：
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通讯作者：
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