Zhang Yonglin, Yu Lezheng, Yang Ming, Han Bin, Luo Jiesi, Jing Runyu
Department of Clinical Pharmacy and Pharmacy Management, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.
School of Chemistry and Materials Science, Guizhou Education University, Guiyang, Guizhou, China.
Proteomics. 2024 Sep;24(17):e2300184. doi: 10.1002/pmic.202300184. Epub 2024 Apr 21.
Unconventional secretory proteins (USPs) are vital for cell-to-cell communication and are necessary for proper physiological processes. Unlike classical proteins that follow the conventional secretory pathway via the Golgi apparatus, these proteins are released using unconventional pathways. The primary modes of secretion for USPs are exosomes and ectosomes, which originate from the endoplasmic reticulum. Accurate and rapid identification of exosome-mediated secretory proteins is crucial for gaining valuable insights into the regulation of non-classical protein secretion and intercellular communication, as well as for the advancement of novel therapeutic approaches. Although computational methods based on amino acid sequence prediction exist for predicting unconventional proteins secreted by exosomes (UPSEs), they suffer from significant limitations in terms of algorithmic accuracy. In this study, we propose a novel approach to predict UPSEs by combining multiple deep learning models that incorporate both protein sequences and evolutionary information. Our approach utilizes a convolutional neural network (CNN) to extract protein sequence information, while various densely connected neural networks (DNNs) are employed to capture evolutionary conservation patterns.By combining six distinct deep learning models, we have created a superior framework that surpasses previous approaches, achieving an ACC score of 77.46% and an MCC score of 0.5406 on an independent test dataset.
非常规分泌蛋白(USPs)对于细胞间通讯至关重要,是正常生理过程所必需的。与通过高尔基体遵循常规分泌途径的经典蛋白不同,这些蛋白通过非常规途径释放。USPs的主要分泌方式是外泌体和胞外体,它们起源于内质网。准确快速地识别外泌体介导的分泌蛋白对于深入了解非经典蛋白分泌和细胞间通讯的调控,以及推动新型治疗方法的发展至关重要。尽管存在基于氨基酸序列预测的计算方法来预测外泌体分泌的非常规蛋白(UPSEs),但它们在算法准确性方面存在显著局限性。在本研究中,我们提出了一种新方法,通过结合多个整合了蛋白质序列和进化信息的深度学习模型来预测UPSEs。我们的方法利用卷积神经网络(CNN)提取蛋白质序列信息,同时采用各种密集连接神经网络(DNN)来捕捉进化保守模式。通过结合六个不同的深度学习模型,我们创建了一个优于先前方法的框架,在独立测试数据集上实现了77.46%的ACC分数和0.5406的MCC分数。