Gao Xin, Wei Zhi, Hakonarson Hakon
Department of Computer Science, New Jersey Institute of Technology, Newark, New Jersey, USA.
Department of Computer Science, New Jersey Institute of Technology, Newark, New Jersey, USA,
Hum Hered. 2018;83(3):163-172. doi: 10.1159/000493215. Epub 2019 Jan 25.
tRNAscan-SE is the leading tool for transfer RNA (tRNA) annotation, which has been widely used in the field. However, tRNAscan-SE can return a significant number of false positives when applied to large sequences. Recently, conventional machine learning methods have been proposed to address this issue, but their efficiency can be still limited due to their dependency on handcrafted features. With the growing availability of large-scale genomic data-sets, deep learning methods, especially convolutional neural networks, have demonstrated excellent power in characterizing sequence patterns in genomic sequences. Thus, we hypothesize that deep learning may bring further improvement for tRNA prediction.
We proposed a new computational approach based on deep neural networks to predict tRNA gene sequences. We designed and investigated various deep neural network architectures. We used the tRNA sequences as positive samples, and the false-positive tRNA sequences predicted by tRNAscan-SE in coding sequences as negative samples, to train and evaluate the proposed models by comparison with the conventional machine learning methods and popular tRNA prediction tools.
Using the one-hot encoding method, our proposed models can extract features without involving extensive manual feature engineering. Our proposed best model outperformed the existing methods under different performance metrics.
The proposed deep learning methods can substantially reduce the false positive output by the state-of-the-art tool tRNAscan-SE. Coupled with tRNAscan-SE, it can serve as a useful complementary tool for tRNA annotation. The application to tRNA prediction demonstrates the superiority of deep learning in automatic feature generation for characterizing sequence patterns.
tRNAscan-SE是用于转运RNA(tRNA)注释的领先工具,已在该领域广泛使用。然而,当应用于大型序列时,tRNAscan-SE会返回大量假阳性结果。最近,有人提出使用传统机器学习方法来解决这个问题,但由于它们对手工制作特征的依赖,其效率仍然可能有限。随着大规模基因组数据集的不断增加,深度学习方法,特别是卷积神经网络,在表征基因组序列中的序列模式方面已显示出卓越的能力。因此,我们假设深度学习可能会为tRNA预测带来进一步的改进。
我们提出了一种基于深度神经网络的新计算方法来预测tRNA基因序列。我们设计并研究了各种深度神经网络架构。我们将tRNA序列用作正样本,并将tRNAscan-SE在编码序列中预测的假阳性tRNA序列用作负样本,通过与传统机器学习方法和流行的tRNA预测工具进行比较来训练和评估所提出的模型。
使用独热编码方法时,我们提出的模型无需进行大量手动特征工程即可提取特征。我们提出的最佳模型在不同性能指标下优于现有方法。
所提出的深度学习方法可以大幅减少最先进工具tRNAscan-SE的假阳性输出。与tRNAscan-SE相结合,它可以作为tRNA注释的有用补充工具。在tRNA预测中的应用证明了深度学习在自动生成用于表征序列模式的特征方面具有优越性。