Position-specific Scoring Matrix Profiles Research Articles

Integrating Pre-Trained protein language model and multiple window scanning deep learning networks for accurate identification of secondary active transporters in membrane proteins

Secondary active transporters play pivotal roles in regulating ion and molecule transport across cell membranes, with implications in diseases like cancer. However, studying transporters via biochemical experiments poses challenges. We propose an effective computational approach to identify secondary active transporters from membrane protein sequences using pre-trained language models and deep learning neural networks.Our dataset comprised 290 secondary active transporters and 5,420 other membrane proteins from UniProt. Three types of features were extracted - one-hot encodings, position-specific scoring matrix profiles, and contextual embeddings from the ProtTrans language model. A multi-window convolutional neural network architecture scanned the ProtTrans embeddings using varying window sizes to capture multi-scale sequence patterns.The proposed model combining ProtTrans embeddings and multi-window convolutional neural networks achieved 86% sensitivity, 99% specificity and 98% overall accuracy in identifying secondary active transporters, outperforming conventional machine learning approaches.This work demonstrates the promise of integrating pre-trained language models like ProtTrans with multi-scale deep neural networks to effectively interpret transporter sequences for functional analysis. Our approach enables more accurate computational identification of secondary active transporters, advancing membrane protein research.

Identification of adaptor proteins by incorporating deep learning and PSSM profiles.

Adaptor proteins, also known as signal transduction adaptor proteins, are important proteins in signal transduction pathways, and play a role in connecting signal proteins for signal transduction between cells. Studies have shown that adaptor proteins are closely related to some diseases, such as tumors and diabetes. Therefore, it is very meaningful to construct a relevant model to accurately identify adaptor proteins. In recent years, many studies have used a position-specific scoring matrix (PSSM) and neural network methods to identify adaptor proteins. However, ordinary neural network models cannot correlate the contextual information in PSSM profiles well, so these studies usually process 20×N (N>20) PSSM into 20×20 dimensions, which results in the loss of a large amount of protein information; This research proposes an efficient method that combines one-dimensional convolution (1-D CNN) and a bidirectional long short-term memory network (biLSTM) to identify adaptor proteins. The complete PSSM profiles are the input of the model, and the complete information of the protein is retained during the training process. We perform cross-validation during model training and test the performance of the model on an independent test set; in the data set with 1224 adaptor proteins and 11,078 non-adaptor proteins, five indicators including specificity, sensitivity, accuracy, area under the receiver operating characteristic curve (AUC) metric and Matthews correlation coefficient (MCC), were employed to evaluate model performance. On the independent test set, the specificity, sensitivity, accuracy and MCC were 0.817, 0.865, 0.823 and 0.465, respectively. Those results show that our method is better than the state-of-the art methods. This study is committed to improve the accuracy of adaptor protein identification, and laid a foundation for further research on diseases related to adaptor protein. This research provided a new idea for the application of deep learning related models in bioinformatics and computational biology.

Pfeature: A Tool for Computing Wide Range of Protein Features and Building Prediction Models.

In the last three decades, a wide range of protein features have been discovered to annotate a protein. Numerous attempts have been made to integrate these features in a software package/platform so that the user may compute a wide range of features from a single source. To complement the existing methods, we developed a method, Pfeature, for computing a wide range of protein features. Pfeature allows to compute more than 200,000 features required for predicting the overall function of a protein, residue-level annotation of a protein, and function of chemically modified peptides. It has six major modules, namely, composition, binary profiles, evolutionary information, structural features, patterns, and model building. Composition module facilitates to compute most of the existing compositional features, plus novel features. The binary profile of amino acid sequences allows to compute the fraction of each type of residue as well as its position. The evolutionary information module allows to compute evolutionary information of a protein in the form of a position-specific scoring matrix profile generated using Position-Specific Iterative Basic Local Alignment Search Tool (PSI-BLAST); fit for annotation of a protein and its residues. A structural module was developed for computing of structural features/descriptors from a tertiary structure of a protein. These features are suitable to predict the therapeutic potential of a protein containing non-natural or chemically modified residues. The model-building module allows to implement various machine learning techniques for developing classification and regression models as well as feature selection. Pfeature also allows the generation of overlapping patterns and features from a protein. A user-friendly Pfeature is available as a web server python library and stand-alone package.

Identifying SNARE Proteins Using an Alignment-Free Method Based on Multiscan Convolutional Neural Network and PSSM Profiles

Background: SNARE proteins play a vital role in membrane fusion and cellular physiology and pathological processes. Many potential therapeutics for mental diseases or even cancer based on SNAREs are also developed. Therefore, there is a dire need to predict the SNAREs for further manipulation of these essential proteins, which demands new and efficient approaches. Methods: Some computational frameworks were proposed to tackle the hurdles of biological methods, which take plenty of time and budget to conduct the identification of SNAREs. However, the performances of existing frameworks were insufficiently satisfied, as they failed to retain the SNARE sequence order and capture the mass hidden features from SNAREs. This paper proposed a novel model constructed on the multiscan convolutional neural network (CNN) and position-specific scoring matrix (PSSM) profiles to address these limitations. We employed and trained our model on the benchmark dataset with fivefold cross-validation and two different independent datasets. Results: Overall, the multiscan CNN was cross-validated on the training set and excelled in the SNARE classification reaching 0.963 in AUC and 0.955 in AUPRC. On top of that, with the sensitivity, specificity, accuracy, and MCC of 0.842, 0.968, 0.955, and 0.767, respectively, our proposed framework outperformed previous models in the SNARE recognition task. Conclusions: It is truly believed that our model can contribute to the discrimination of SNARE proteins and general proteins.

A deep learning-based method for the prediction of DNA interacting residues in a protein.

DNA-protein interaction is one of the most crucial interactions in the biological system, which decides the fate of many processes such as transcription, regulation and splicing of genes. In this study, we trained our models on a training dataset of 646 DNA-binding proteins having 15636 DNA interacting and 298503 non-interacting residues. Our trained models were evaluated on an independent dataset of 46 DNA-binding proteins having 965 DNA interacting and 9911 non-interacting residues. All proteins in the independent dataset have less than 30% of sequence similarity with proteins in the training dataset. A wide range of traditional machine learning and deep learning (1D-CNN) techniques-based models have been developed using binary, physicochemical properties and Position-Specific Scoring Matrix (PSSM)/evolutionary profiles. In the case of machine learning technique, eXtreme Gradient Boosting-based model achieved a maximum area under the receiver operating characteristics (AUROC) curve of 0.77 on the independent dataset using PSSM profile. Deep learning-based model achieved the highest AUROC of 0.79 on the independent dataset using a combination of all three profiles. We evaluated the performance of existing methods on the independent dataset and observed that our proposed method outperformed all the existing methods. In order to facilitate scientific community, we developed standalone software and web server, which are accessible from https://webs.iiitd.edu.in/raghava/dbpred.

Novel PSSM-Based Approaches for Gene Identification Using Support Vector Machine

By understanding the function of each protein encoded in genome, the molecular mechanism of the cell can be recognized. In genome annotation field, several methods or techniques have been developed to locate or predict the patterns of genes in genome sequence. However, recognizing corresponding gene of a given protein sequence using conventional tools is inherently complicated and error prone. This paper first focuses on the issue of gene prediction and its challenges. The authors then present a novel method for identifying genes that involves a two-step process. First the research presents new features extracted from protein sequences using a position specific scoring matrix (PSSM). The PSSM profiles are converted into uniform numeric representation. Then, a new structured approach has been applied on PSSM vector which uses a decision tree-based technique for obtaining rules. Finally, the rules of single class are joined together to form a matrix which is then given as an input to SVM for classification purpose. The rules derived from algorithm correspond to genes. The authors also introduce another approach for predicting genes based on PSSM using SVM. Both the methods have been implemented on genome DNAset dataset. Empirical evaluation shows that PSSM based SAFARI approach produces better results.

FAD-BERT: Improved prediction of FAD binding sites using pre-training of deep bidirectional transformers

The electron transport chain is a series of protein complexes embedded in the process of cellular respiration, which is an important process to transfer electrons and other macromolecules throughout the cell. Identifying Flavin Adenine Dinucleotide (FAD) binding sites in the electron transport chain is vital since it helps biological researchers precisely understand how electrons are produced and are transported in cells. This study distills and analyzes the contextualized word embedding from pre-trained BERT models to explore similarities in natural language and protein sequences. Thereby, we propose a new approach based on Pre-training of Bidirectional Encoder Representations from Transformers (BERT), Position-specific Scoring Matrix profiles (PSSM), Amino Acid Index database (AAIndex) to predict FAD-binding sites from the transport proteins which are found in nature recently. Our proposed approach archives 85.14% accuracy and improves accuracy by 11%, with Matthew's correlation coefficient of 0.39 compared to the previous method on the same independent set. We also deploy a web server that identifies FAD-binding sites in electron transporters available for academics at http://140.138.155.216/fadbert/.

PL-search: a profile-link-based search method for protein remote homology detection

Protein remote homology detection is a fundamental and important task for protein structure and function analysis. Several search methods have been proposed to improve the detection performance of the remote homologues and the accuracy of ranking lists. The position-specific scoring matrix (PSSM) profile and hidden Markov model (HMM) profile can contribute to improving the performance of the state-of-the-art search methods. In this paper, we improved the profile-link (PL) information for constructing PSSM or HMM profiles, and proposed a PL-based search method (PL-search). In PL-search, more robust PLs are constructed through the double-link and iterative extending strategies, and an accurate similarity score of sequence pairs is calculated from the two-level Jaccard distance for remote homologues. We tested our method on two widely used benchmark datasets. Our results show that whether HHblits, JackHMMER or position-specific iterated-BLAST is used, PL-search obviously improves the search performance in terms of ranking quality as well as the number of detected remote homologues. For ease of use of PL-search, both its stand-alone tool and the web server are constructed, which can be accessed at http://bliulab.net/PL-search/.

Classification of adaptor proteins using recurrent neural networks and PSSM profiles

BackgroundAdaptor proteins are carrier proteins that play a crucial role in signal transduction. They commonly consist of several modular domains, each having its own binding activity and operating by forming complexes with other intracellular-signaling molecules. Many studies determined that the adaptor proteins had been implicated in a variety of human diseases. Therefore, creating a precise model to predict the function of adaptor proteins is one of the vital tasks in bioinformatics and computational biology. Few computational biology studies have been conducted to predict the protein functions, and in most of those studies, position specific scoring matrix (PSSM) profiles had been used as the features to be fed into the neural networks. However, the neural networks could not reach the optimal result because the sequential information in PSSMs has been lost. This study proposes an innovative approach by incorporating recurrent neural networks (RNNs) and PSSM profiles to resolve this problem.ResultsCompared to other state-of-the-art methods which had been applied successfully in other problems, our method achieves enhancement in all of the common measurement metrics. The area under the receiver operating characteristic curve (AUC) metric in prediction of adaptor proteins in the cross-validation and independent datasets are 0.893 and 0.853, respectively.ConclusionsThis study opens a research path that can promote the use of RNNs and PSSM profiles in bioinformatics and computational biology. Our approach is reproducible by scientists that aim to improve the performance results of different protein function prediction problems. Our source code and datasets are available at https://github.com/ngphubinh/adaptors.

Fertility-GRU: Identifying Fertility-Related Proteins by Incorporating Deep-Gated Recurrent Units and Original Position-Specific Scoring Matrix Profiles.

Protein function prediction is one of the well-known problems in proteome research, attracting the attention of numerous researchers. However, the implementation of deep neural networks, which helps to increase the protein function prediction, still poses a big challenge. This study proposes a deep learning approach namely Fertility-GRU that incorporates gated recurrent units and position-specific scoring matrix profiles to predict the function of fertility-related protein, which is a highly crucial biological function. Fertility-related proteins also have been proven to be important in many biological entities (i.e., bone marrow and peripheral blood, postnatal mammalian ovary) and parameters (i.e., daily sperm production). As a result, our model can achieve a cross-validation accuracy of 85.8% and an independent accuracy of 91.1%. We also solve the problem of overfitting in the data set by adding dropout layers in the deep learning model. The independent testing results showed sensitivity, specificity, and Matthews correlation coefficient (MCC) values of 90.5%, 91.7%, and 0.82, respectively. Fertility-GRU demonstrates superiority in performance against the state-of-the-art predictor on the same data set. In our proposed study, we provided a method that enables more proteins to be discovered, especially proteins associated with fertility. Moreover, our achievement could promote the use of recurrent networks and gated recurrent units in proteome research. The source code and data set are freely accessible via https://github.com/khanhlee/fertility-gru .

Identification of clathrin proteins by incorporating hyperparameter optimization in deep learning and PSSM profiles

Background and ObjectivesClathrin is an adaptor protein that serves as the principal element of the vesicle-coating complex and is important for the membrane cleavage to dispense the invaginated vesicle from the plasma membrane. The functional loss of clathrins has been tied to a lot of human diseases, i.e., neurodegenerative disorders, cancer, Alzheimer's diseases, and so on. Therefore, creating a precise model to identify its functions is a crucial step towards understanding human diseases and designing drug targets. MethodsWe present a deep learning model using a two-dimensional convolutional neural network (CNN) and position-specific scoring matrix (PSSM) profiles to identify clathrin proteins from high throughput sequences. Traditionally, the 2D CNNs take images as an input so we treated the PSSM profile with a 20 × 20 matrix as an image of 20 × 20 pixels. The input PSSM profile was then connected to our 2D CNN in which we set a variety of parameters to improve the performance of the model. Based on the 10-fold cross-validation results, hyper-parameter optimization process was employed to find the best model for our dataset. Finally, an independent dataset was used to assess the predictive ability of the current model. ResultsOur model could identify clathrin proteins with sensitivity of 92.2%, specificity of 91.2%, accuracy of 91.8%, and MCC of 0.83 in the independent dataset. Compared to state-of-the-art traditional neural networks, our method achieved a significant improvement in all typical measurement metrics. ConclusionsThroughout the proposed study, we provide an effective tool for investigating clathrin proteins and our achievement could promote the use of deep learning in biomedical research. We also provide source codes and dataset freely at https://www.github.com/khanhlee/deep-clathrin/.

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.

SNARE-CNN: a 2D convolutional neural network architecture to identify SNARE proteins from high-throughput sequencing data.

Deep learning has been increasingly and widely used to solve numerous problems in various fields with state-of-the-art performance. It can also be applied in bioinformatics to reduce the requirement for feature extraction and reach high performance. This study attempts to use deep learning to predict SNARE proteins, which is one of the most vital molecular functions in life science. A functional loss of SNARE proteins has been implicated in a variety of human diseases (e.g., neurodegenerative, mental illness, cancer, and so on). Therefore, creating a precise model to identify their functions is a crucial problem for understanding these diseases, and designing the drug targets. Our SNARE-CNN model which uses two-dimensional convolutional neural networks and position-specific scoring matrix profiles could identify SNARE proteins with achieved sensitivity of 76.6%, specificity of 93.5%, accuracy of 89.7%, and MCC of 0.7 in cross-validation dataset. We also evaluate the performance of our model via an independent dataset and the result shows that we are able to solve the overfitting problem. Compared with other state-of-the-art methods, this approach achieved significant improvement in all of the metrics. Throughout the proposed study, we provide an effective model for identifying SNARE proteins and a basis for further research that can apply deep learning in bioinformatics, especially in protein function prediction. SNARE-CNN are freely available at https://github.com/khanhlee/snare-cnn.

An ensemble method for multi-type Gram-negative bacterial secreted protein prediction by integrating different PSSM-based features

ABSTRACTIn Gram-negative bacteria, a wide range of proteins are secreted by highly specialized secretion systems. These secreted proteins play essential roles in the response of bacteria to their environment and also in several physiological processes such as adhesion, pathogenicity, adaptation and survival. Therefore, identifying secreted proteins in Gram-negative bacteria may assist in understanding the secretion mechanism and development of new antimicrobial strategies. Considering that a single-feature model is less likely to comprehensively cover this information, three kinds of feature models were used in this paper to represent protein samples by composition analysis, correlation analysis and smoothing encoding method on position-specific scoring matrix profiles. A support vector machine-based ensemble method with these hybrid features was developed to predict multi-type Gram-negative bacterial secreted proteins. Finally, our method achieves overall accuracies of 97.09% and 96.51% using an independent dataset test and jackknife test on a public test dataset, which are 3.49% and 2.32% higher, respectively, than results obtained by other methods. These results show the effectiveness and stability of the proposed ensemble method. It is anticipated that our method will provide useful information for further research on bacterial secreted proteins and secreted systems.

Using two-dimensional convolutional neural networks for identifying GTP binding sites in Rab proteins

Deep learning has been increasingly and widely used to solve numerous problems in various fields with state-of-the-art performance. It can also be applied in bioinformatics to reduce the requirement for feature extraction and reach high performance. This study attempts to use deep learning to predict GTP binding sites in Rab proteins, which is one of the most vital molecular functions in life science. A functional loss of GTP binding sites in Rab proteins has been implicated in a variety of human diseases (choroideremia, intellectual disability, cancer, Parkinson's disease). Therefore, creating a precise model to identify their functions is a crucial problem for understanding these diseases and designing the drug targets. Our deep learning model with two-dimensional convolutional neural network and position-specific scoring matrix profiles could identify GTP binding residues with achieved sensitivity of 92.3%, specificity of 99.8%, accuracy of 99.5%, and MCC of 0.92 for independent dataset. Compared with other published works, this approach achieved a significant improvement. Throughout the proposed study, we provide an effective model for predicting GTP binding sites in Rab proteins and a basis for further research that can apply deep learning in bioinformatics, especially in nucleotide binding site prediction.

Computational identification of vesicular transport proteins from sequences using deep gated recurrent units architecture

Protein function prediction is one of the most well-studied topics, attracting attention from countless researchers in the field of computational biology. Implementing deep neural networks that help improve the prediction of protein function, however, is still a major challenge. In this research, we suggested a new strategy that includes gated recurrent units and position-specific scoring matrix profiles to predict vesicular transportation proteins, a biological function of great importance. Although it is difficult to discover its function, our model is able to achieve accuracies of 82.3% and 85.8% in the cross-validation and independent dataset, respectively. We also solve the problem of imbalance in the dataset via tuning class weight in the deep learning model. The results generated showed sensitivity, specificity, MCC, and AUC to have values of 79.2%, 82.9%, 0.52, and 0.861, respectively. Our strategy shows superiority in results on the same dataset against all other state-of-the-art algorithms. In our suggested research, we have suggested a technique for the discovery of more proteins, particularly proteins connected with vesicular transport. In addition, our accomplishment could encourage the use of gated recurrent units architecture in protein function prediction.

PredT4SE-Stack: Prediction of Bacterial Type IV Secreted Effectors From Protein Sequences Using a Stacked Ensemble Method.

Gram-negative bacteria use various secretion systems to deliver their secreted effectors. Among them, type IV secretion system exists widely in a variety of bacterial species, and secretes type IV secreted effectors (T4SEs), which play vital roles in host-pathogen interactions. However, experimental approaches to identify T4SEs are time- and resource-consuming. In the present study, we aim to develop an in silico stacked ensemble method to predict whether a protein is an effector of type IV secretion system or not based on its sequence information. The protein sequences were encoded by the feature of position specific scoring matrix (PSSM)-composition by summing rows that correspond to the same amino acid residues in PSSM profiles. Based on the PSSM-composition features, we develop a stacked ensemble model PredT4SE-Stack to predict T4SEs, which utilized an ensemble of base-classifiers implemented by various machine learning algorithms, such as support vector machine, gradient boosting machine, and extremely randomized trees, to generate outputs for the meta-classifier in the classification system. Our results demonstrated that the framework of PredT4SE-Stack was a feasible and effective way to accurately identify T4SEs based on protein sequence information. The datasets and source code of PredT4SE-Stack are freely available at http://xbioinfo.sjtu.edu.cn/PredT4SE_Stack/index.php.

Improving Prediction of Self-interacting Proteins Using Stacked Sparse Auto-Encoder with PSSM profiles.

Self-interacting proteins (SIPs) play a significant role in the execution of most important molecular processes in cells, such as signal transduction, gene expression regulation, immune response and enzyme activation. Although the traditional experimental methods can be used to generate SIPs data, it is very expensive and time-consuming based only on biological technique. Therefore, it is important and urgent to develop an efficient computational method for SIPs detection. In this study, we present a novel SIPs identification method based on machine learning technology by combing the Zernike Moments (ZMs) descriptor on Position Specific Scoring Matrix (PSSM) with Probabilistic Classification Vector Machines (PCVM) and Stacked Sparse Auto-Encoder (SSAE). More specifically, an efficient feature extraction technique called ZMs is firstly utilized to generate feature vectors on Position Specific Scoring Matrix (PSSM); Then, Deep neural network is employed for reducing the feature dimensions and noise; Finally, the Probabilistic Classification Vector Machine is used to execute the classification. The prediction performance of the proposed method is evaluated on S.erevisiae and Human SIPs datasets via cross-validation. The experimental results indicate that the proposed method can achieve good accuracies of 92.55% and 97.47%, respectively. To further evaluate the advantage of our scheme for SIPs prediction, we also compared the PCVM classifier with the Support Vector Machine (SVM) and other existing techniques on the same data sets. Comparison results reveal that the proposed strategy is outperforms other methods and could be a used tool for identifying SIPs.

Analysis and prediction of single-stranded and double-stranded DNA binding proteins based on protein sequences

BackgroundDNA-binding proteins perform important functions in a great number of biological activities. DNA-binding proteins can interact with ssDNA (single-stranded DNA) or dsDNA (double-stranded DNA), and DNA-binding proteins can be categorized as single-stranded DNA-binding proteins (SSBs) and double-stranded DNA-binding proteins (DSBs). The identification of DNA-binding proteins from amino acid sequences can help to annotate protein functions and understand the binding specificity.In this study, we systematically consider a variety of schemes to represent protein sequences: OAAC (overall amino acid composition) features, dipeptide compositions, PSSM (position-specific scoring matrix profiles) and split amino acid composition (SAA), and then we adopt SVM (support vector machine) and RF (random forest) classification model to distinguish SSBs from DSBs.ResultsOur results suggest that some sequence features can significantly differentiate DSBs and SSBs. Evaluated by 10 fold cross-validation on the benchmark datasets, our prediction method can achieve the accuracy of 88.7% and AUC (area under the curve) of 0.919. Moreover, our method has good performance in independent testing.ConclusionsUsing various sequence-derived features, a novel method is proposed to distinguish DSBs and SSBs accurately. The method also explores novel features, which could be helpful to discover the binding specificity of DNA-binding proteins.

POSSUM: a bioinformatics toolkit for generating numerical sequence feature descriptors based on PSSM profiles.

Evolutionary information in the form of a Position-Specific Scoring Matrix (PSSM) is a widely used and highly informative representation of protein sequences. Accordingly, PSSM-based feature descriptors have been successfully applied to improve the performance of various predictors of protein attributes. Even though a number of algorithms have been proposed in previous studies, there is currently no universal web server or toolkit available for generating this wide variety of descriptors. Here, we present POSSUM ( Po sition- S pecific S coring matrix-based feat u re generator for m achine learning), a versatile toolkit with an online web server that can generate 21 types of PSSM-based feature descriptors, thereby addressing a crucial need for bioinformaticians and computational biologists. We envisage that this comprehensive toolkit will be widely used as a powerful tool to facilitate feature extraction, selection, and benchmarking of machine learning-based models, thereby contributing to a more effective analysis and modeling pipeline for bioinformatics research. http://possum.erc.monash.edu/ . trevor.lithgow@monash.edu or jiangning.song@monash.edu. Supplementary data are available at Bioinformatics online.