Identification of efflux proteins based on contextual representations with deep bidirectional transformer encoders.

Efflux proteins are the transport proteins expressed in the plasma membrane, which are involved in the movement of unwanted toxic substances through specific efflux pumps. Several studies based on computational approaches have been proposed to predict transport proteins and thereby to understand the mechanism of the movement of ions across cell membranes. However, few methods were developed to identify efflux proteins. This paper presents an approach based on the contextualized word embeddings from Bidirectional Encoder Representations from Transformers (BERT) with the Support Vector Machine (SVM) classifier. BERT is the most effective pre-trained language model that performs exceptionally well on several Natural Language Processing (NLP) tasks. Therefore, the contextualized representations from BERT were implemented to incorporate multiple interpretations of identical amino acids in the sequence. A dataset of efflux proteins with annotations was first established. The feature vectors were extracted by transferring protein data through the hidden layers of the pre-trained model. Our proposed method was trained on complete training datasets to identify efflux proteins and achieved the accuracies of 94.15% and 87.13% in the independent tests on membrane and transport datasets, respectively. This study opens a research avenue for the implementation of contextualized word embeddings in Bioinformatics and Computational Biology.

DeepIon: Deep learning approach for classifying ion transporters and ion channels from membrane proteins.

The movement of ions across the cell membrane is an essential for many biological processes. This study is focused on ion channels and ion transporters (pumps) as types of border guards control the incessant traffic of ions across cell membranes. Ion channels and ion transporters function to regulate membrane potential and electrical signaling and play important roles in cell proliferation, migration, apoptosis, and differentiation. In their behaviors, it is found that ion channels differ significantly from ion transporters. Therefore, a method for automatically classifying ion transporters and ion channels from membrane proteins is proposed by training deep neural networks and using the position-specific scoring matrix profile as an input. The key of novelty is the three-stage approach, in which five techniques for data normalization are used; next three imbalanced data techniques are applied to the minority classes and then, six classifiers are compared with the proposed method. © 2019 Wiley Periodicals, Inc.

DeepEfflux: a 2D convolutional neural network model for identifying families of efflux proteins in transporters.

Motivation: Efflux protein plays a key role in pumping xenobiotics out of the cells. The prediction of efflux family proteins involved in transport process of compounds is crucial for understanding family structures, functions and energy dependencies. Many methods have been proposed to classify efflux pump transporters without considerations of any pump specific of efflux protein families. In other words, efflux proteins protect cells from extrusion of foreign chemicals. Moreover, almost all efflux protein families have the same structure based on the analysis of significant motifs. The motif sequences consisting of the same amount of residues will have high degrees of residue similarity and thus will affect the classification process. Consequently, it is challenging but vital to recognize the structures and determine energy dependencies of efflux protein families. In order to efficiently identify efflux protein families with considering about pump specific, we developed a 2 D convolutional neural network (2 D CNN) model called DeepEfflux. DeepEfflux tried to capture the motifs of sequences around hidden target residues to use as hidden features of families. In addition, the 2 D CNN model uses a position-specific scoring matrix (PSSM) as an input. Three different datasets, each for one family of efflux protein, was fed into DeepEfflux, and then a 5-fold cross validation approach was used to evaluate the training performance. Results: The model evaluation results show that DeepEfflux outperforms traditional machine learning algorithms. Furthermore, the accuracy of 96.02%, 94.89% and 90.34% for classes A, B and C, respectively, in the independent test results show that our model can perform well and can be used as a reliable tool for identifying families of efflux proteins in transporters. Availability and implementation: The online version of deepefflux is available at http://deepefflux.irit.fr. The source code of deepefflux is available both on the deepefflux website and at http://140.138.155.216/deepefflux/. Supplementary information: Supplementary data are available at Bioinformatics online.

ActTRANS: Functional classification in active transport proteins based on transfer learning and contextual representations.

MOTIVATION: Primary and secondary active transport are two types of active transport that involve using energy to move the substances. Active transport mechanisms do use proteins to assist in transport and play essential roles to regulate the traffic of ions or small molecules across a cell membrane against the concentration gradient. In this study, the two main types of proteins involved in such transport are classified from transmembrane transport proteins. We propose a Support Vector Machine (SVM) with contextualized word embeddings from Bidirectional Encoder Representations from Transformers (BERT) to represent protein sequences. BERT is a powerful model in transfer learning, a deep learning language representation model developed by Google and one of the highest performing pre-trained model for Natural Language Processing (NLP) tasks. The idea of transfer learning with pre-trained model from BERT is applied to extract fixed feature vectors from the hidden layers and learn contextual relations between amino acids in the protein sequence. Therefore, the contextualized word representations of proteins are introduced to effectively model complex structures of amino acids in the sequence and the variations of these amino acids in the context. By generating context information, we capture multiple meanings for the same amino acid to reveal the importance of specific residues in the protein sequence. RESULTS: The performance of the proposed method is evaluated using five-fold cross-validation and independent test. The proposed method achieves an accuracy of 85.44 %, 88.74 % and 92.84 % for Class-1, Class-2, and Class-3, respectively. Experimental results show that this approach can outperform from other feature extraction methods using context information, effectively classify two types of active transport and improve the overall performance.

DeepSIRT: A deep neural network for identification of sirtuin targets and their subcellular localizations.

Sirtuins are a family of proteins that play a key role in regulating a wide range of cellular processes including DNA regulation, metabolism, aging/longevity, cell survival, apoptosis, and stress resistance. Sirtuins are protein deacetylases and include in the class III family of histone deacetylase enzymes (HDACs). The class III HDACs contains seven members of the sirtuin family from SIRT1 to SIRT7. The seven members of the sirtuin family have various substrates and are present in nearly all subcellular localizations including the nucleus, cytoplasm, and mitochondria. In this study, a deep neural network approach using one-dimensional Convolutional Neural Networks (CNN) was proposed to build a prediction model that can accurately identify the outcome of the sirtuin protein by targeting their subcellular localizations. Therefore, the function and localization of sirtuin targets were analyzed and annotated to compartmentalize into distinct subcellular localizations. We further reduced the sequence similarity between protein sequences and three feature extraction methods were applied in datasets. Finally, the proposed method has been tested and compared with various machine-learning algorithms. The proposed method is validated on two independent datasets and showed an average of up to 85.77 % sensitivity, 97.32 % specificity, and 0.82 MCC for seven members of the sirtuin family of proteins.

GT-Finder: Classify the family of glucose transporters with pre-trained BERT language models.

Recently, language representation models have drawn a lot of attention in the field of natural language processing (NLP) due to their remarkable results. Among them, BERT (Bidirectional Encoder Representations from Transformers) has proven to be a simple, yet powerful language model that has achieved novel state-of-the-art performance. BERT adopted the concept of contextualized word embeddings to capture the semantics and context in which words appear. We utilized pre-trained BERT models to extract features from protein sequences for discriminating three families of glucose transporters: the major facilitator superfamily of glucose transporters (GLUTs), the sodium-glucose linked transporters (SGLTs), and the sugars will eventually be exported transporters (SWEETs). We treated protein sequences as sentences and transformed them into fixed-length meaningful vectors where a 768- or 1024-dimensional vector represents each amino acid. We observed that BERT-Base and BERT-Large models improved the performance by more than 4% in terms of average sensitivity and Matthews correlation coefficient (MCC), indicating the efficiency of this approach. We also developed a bidirectional transformer-based protein model (TransportersBERT) for comparison with existing pre-trained BERT models.