Wan Cen, Lees Jonathan G, Minneci Federico, Orengo Christine A, Jones David T
Department of Computer Science, University College London, London, United Kingdom.
Biomedical Data Science Laboratory, The Francis Crick Institute, London, United Kingdom.
PLoS Comput Biol. 2017 Oct 18;13(10):e1005791. doi: 10.1371/journal.pcbi.1005791. eCollection 2017 Oct.
Accurate gene or protein function prediction is a key challenge in the post-genome era. Most current methods perform well on molecular function prediction, but struggle to provide useful annotations relating to biological process functions due to the limited power of sequence-based features in that functional domain. In this work, we systematically evaluate the predictive power of temporal transcription expression profiles for protein function prediction in Drosophila melanogaster. Our results show significantly better performance on predicting protein function when transcription expression profile-based features are integrated with sequence-derived features, compared with the sequence-derived features alone. We also observe that the combination of expression-based and sequence-based features leads to further improvement of accuracy on predicting all three domains of gene function. Based on the optimal feature combinations, we then propose a novel multi-classifier-based function prediction method for Drosophila melanogaster proteins, FFPred-fly+. Interpreting our machine learning models also allows us to identify some of the underlying links between biological processes and developmental stages of Drosophila melanogaster.
准确的基因或蛋白质功能预测是后基因组时代的一项关键挑战。目前大多数方法在分子功能预测方面表现良好,但由于该功能域中基于序列的特征能力有限,难以提供与生物过程功能相关的有用注释。在这项工作中,我们系统地评估了果蝇中时间转录表达谱对蛋白质功能预测的预测能力。我们的结果表明,与仅基于序列的特征相比,当基于转录表达谱的特征与基于序列衍生的特征相结合时,在预测蛋白质功能方面具有显著更好的性能。我们还观察到,基于表达的特征和基于序列的特征相结合可进一步提高预测基因功能所有三个域的准确性。基于最优特征组合,我们随后提出了一种针对果蝇蛋白质的基于多分类器的新型功能预测方法FFPred-fly+。对我们的机器学习模型进行解释还使我们能够识别果蝇生物过程与发育阶段之间的一些潜在联系。