Predicting essential genes in fungal genomes
Predicting essential genes in fungal genomes
复制标题
DOI：
10.1101/gr.5144106
复制
发表时间：
2006-09-01
期刊：
影响因子：
7
通讯作者：
Gerstein, Mark
中科院分区：
文献类型：
--
作者：
Seringhaus, Michael;Paccanaro, Alberto;Gerstein, Mark
生物体的生存需要必需基因，而识别病原体中这些基因的能力对于定向药物开发至关重要。通过计算方法预测必需基因很有吸引力，因为它规避了昂贵且困难的实验筛选。大多数此类预测都是基于与模型生物中经过实验验证的必需基因的同源映射。我们在这里提出了一种不同的方法，该方法完全依赖于基因的序列特征来估计重要性，并提供了一种有前途的方法来识别未经研究或未培养的生物体中的必需基因。我们确定了 14 个可能与必要性相关的特征序列特征，例如定位信号、密码子适应、GC 含量和整体疏水性。使用经过充分表征的面包酵母酿酒酵母，我们采用简单的贝叶斯框架来衡量每个特征与重要性的相关性。然后，我们利用这 14 个特征来学习能够预测必需基因的机器学习分类器的参数。我们在酿酒酵母中已知的必需基因上训练了我们的分类器，并将其应用于密切相关且相对未经研究的酵母 Saccharomyces mikatae。我们通过两种方式评估预测的成功：首先，我们将所有预测与通过这两个物种之间的同源图谱生成的预测进行比较。其次，我们通过 S. mikatae 中的八个体内敲除验证了我们的预测的子集，并且我们在此提出了该物种中第一个经过实验证实的必需基因。
Essential genes are required for an organism's viability, and the ability to identify these genes in pathogens is crucial to directed drug development. Predicting essential genes through computational methods is appealing because it circumvents expensive and difficult experimental screens. Most such prediction is based on homology mapping to experimentally verified essential genes in model organisms. We present here a different approach, one that relies exclusively on sequence features of a gene to estimate essentiality and offers a promising way to identify essential genes in unstudied or uncultured organisms. We identified 14 characteristic sequence features potentially associated with essentiality, such as localization signals, codon adaptation, GC content, and overall hydrophobicity. Using the well- characterized baker's yeast Saccharomyces cerevisiae, we employed a simple Bayesian framework to measure the correlation of each of these features with essentiality. We then employed the 14 features to learn the parameters of a machine learning classifier capable of predicting essential genes. We trained our classifier on known essential genes in S. cerevisiae and applied it to the closely related and relatively unstudied yeast Saccharomyces mikatae. We assessed predictive success in two ways: First, we compared all of our predictions with those generated by homology mapping between these two species. Second, we verified a subset of our predictions with eight in vivo knockouts in S. mikatae, and we present here the first experimentally confirmed essential genes in this species.