Stärk Hannes, Dallago Christian, Heinzinger Michael, Rost Burkhard
Department of Informatics, Bioinformatics & Computational Biology-i12, TUM (Technical University of Munich), 85748 Munich, Germany.
TUM Graduate School, Center of Doctoral Studies in Informatics and its Applications (CeDoSIA), 85748 Munich, Germany.
Bioinform Adv. 2021 Nov 19;1(1):vbab035. doi: 10.1093/bioadv/vbab035. eCollection 2021.
Although knowing where a protein functions in a cell is important to characterize biological processes, this information remains unavailable for most known proteins. Machine learning narrows the gap through predictions from expert-designed input features leveraging information from multiple sequence alignments (MSAs) that is resource expensive to generate. Here, we showcased using embeddings from protein language models for competitive localization prediction without MSAs. Our lightweight deep neural network architecture used a softmax weighted aggregation mechanism with linear complexity in sequence length referred to as light attention. The method significantly outperformed the state-of-the-art (SOTA) for 10 localization classes by about 8 percentage points (Q10). So far, this might be the highest improvement of over MSAs. Our new test set highlighted the limits of standard static datasets: while inviting new models, they might not suffice to claim improvements over the SOTA.
The novel models are available as a web-service at http://embed.protein.properties. Code needed to reproduce results is provided at https://github.com/HannesStark/protein-localization. Predictions for the human proteome are available at https://zenodo.org/record/5047020.
Supplementary data are available at online.
尽管了解蛋白质在细胞中的功能位置对于表征生物过程很重要,但对于大多数已知蛋白质来说,此类信息仍然无法获取。机器学习通过利用来自多序列比对(MSA)的信息,根据专家设计的输入特征进行预测,从而缩小了这一差距,不过生成多序列比对的资源成本很高。在此,我们展示了使用蛋白质语言模型的嵌入进行无MSA的竞争性定位预测。我们的轻量级深度神经网络架构使用了一种具有线性序列长度复杂度的softmax加权聚合机制,称为轻注意力机制。该方法在10个定位类别上显著优于当前最先进的方法(SOTA)约8个百分点(Q10)。到目前为止,这可能是相对于多序列比对方法的最大提升。我们的新测试集突出了标准静态数据集的局限性:虽然能够引入新模型,但它们可能不足以宣称相对于SOTA有改进。
补充数据可在网上获取。