Position-specific Frequency Matrix Research Articles

Protein Secondary Structure Prediction Using Cascaded Feature Learning Model

The protein secondary structure prediction (PSSP) is pivotal for predicting tertiary structure, which is proliferating in demand for drug design and development. Further, it can be used to learn different protein functions. Although there are many computational methods for protein structure prediction, none of them have succeeded 100% in solving the protein structure prediction problem. This paper proposes a deep learning model, namely Cascaded Feature Learning Model (CFLM) that uses a multi-stage transfer learning approach based on the Residual Dense Network (RDN) for predicting protein secondary structure. The model is trained with different protein datasets at various levels of transfer learning and accepts selected protein features such as solvent accessibility, physicochemical properties, PSSM (position-specific scoring matrix), and PSFM (position-specific frequency matrix) as input. The Q3 and Q8 accuracy obtained on CASP 13 and 14 benchmark datasets with the proposed approach are 91.23% and 91.45%, and 76.83% and 78.04%, respectively. The performance of CFLM is also compared with some of the recent PSSP approaches and it is observed that the proposed approach improves the prediction accuracy by 2.8% in terms of Q3 and 1.81% in terms of Q8 in the CASP 14 dataset.

Predicting RNA solvent accessibility from multi-scale context feature via multi-shot neural network

Knowledge of RNA solvent accessibility has recently become attractive due to the increasing awareness of its importance for key biological process. Accurately predicting the solvent accessibility of RNA is crucial for understanding its 3D structure and biological function. In this study, we develop a novel computational method, termed M2pred, for accurately predicting the solvent accessibility of RNA from sequence-based multi-scale context feature. In M2pred, three single-view features, i.e., base-pairing probabilities, position-specific frequency matrix, and a binary one-hot encoding, are first generated as three feature sources, and immediately concatenated to engender a super feature. Secondly, for the super feature, the matrix-format features of each nucleotide are extracted using an initialized sliding window technique, and regularly stacked into a cube-format feature. Then, using multi-scale context feature extraction strategy, a pyramid feature constructed of contextual feature of four scales related to target nucleotides is extracted from the cube-format feature. Finally, a customized multi-shot neural network framework, which is equipped with four different scales of receptive fields mainly integrating several residual attention blocks, is designed to dig discrimination information from the contextual pyramid feature. Experimental results demonstrate that the proposed M2pred achieve a high prediction performance and outperforms existing state-of-the-art prediction methods of RNA solvent accessibility.

Improved protein relative solvent accessibility prediction using deep multi-view feature learning framework

The accurate prediction of the relative solvent accessibility of a protein is critical to understanding its 3D structure and biological function. In this study, a novel deep multi-view feature learning (DMVFL) framework that integrates three different neural network units, i.e., bidirectional long short-term memory recurrent neural network, squeeze-and-excitation, and fully-connected hidden layer, with four sequence-based single-view features, i.e., position-specific scoring matrix, position-specific frequency matrix, predicted secondary structure, and roughly predicted three-state relative solvent accessibility probability, is developed to accurately predict relative solvent accessibility information of protein. On the basis of this newly developed framework, one new protein relative solvent accessibility predictor was proposed and called DMVFL-RSA, which employs a customized multiple feedback mechanism that helps to extract discriminative information embedded in the four single-view features. In benchmark tests on TEST524 and CASP14-derived (CASP14set) datasets, DMVFL-RSA outperforms other existing state-of-the-art protein relative solvent accessibility predictors when predicting two-state (exposure threshold of 25%), three-state (exposure thresholds of 9% and 36%), and four-state (exposure thresholds of 4%, 25%, and 50%) discrete values. For real-valued prediction on TEST524 and CASP14set, DMVFL-RSA has also gained high Pearson correlation coefficient values, indicating a positive correlation between the predicted and native relative solvent accessibility. Detailed analyses show that the major advantages of DMVFL-RSA lie in the high efficiency of the DMVFL framework, the applied multiple feedback mechanism, and the strong sensitivity of the sequence-based features. The web server of DMVFL-RSA is freely available at https://jun-csbio.github.io/DMVFL-RSA/for academic use. The standalone package of DMVFL-RSA is downloadable at https://github.com/XueQiangFan/DMVFL-RSA.

Accurate prediction of protein-ATP binding residues using position-specific frequency matrix

Knowledge of protein-ATP interaction can help for protein functional annotation and drug discovery. Accurately identifying protein-ATP binding residues is an important but challenging task to gain the knowledge of protein-ATP interactions, especially for the case where only protein sequence information is given. In this study, we propose a novel method, named DeepATPseq, to predict protein-ATP binding residues without using any information about protein three-dimension structure or sequence-derived structural information. In DeepATPseq, the HHBlits-generated position-specific frequency matrix (PSFM) profile is first employed to extract the feature information of each residue. Then, for each residue, the PSFM-based feature is fed into two prediction models, which are generated by the algorithms of deep convolutional neural network (DCNN) and support vector machine (SVM) separately. The final ATP-binding probability of the corresponding residue is calculated by the weighted sum of the outputted values of DCNN-based and SVM-based models. Experimental results on the independent validation data set demonstrate that DeepATPseq could achieve an accuracy of 77.71%, covering 57.42% of all ATP-binding residues, while achieving a Matthew's correlation coefficient value (0.655) that is significantly higher than that of existing sequence-based methods and comparable to that of the state-of-the-art structure-based predictors. Detailed data analysis show that the major advantage of DeepATPseq lies at the combination utilization of DCNN and SVM that helps dig out more discriminative information from the PSFM profiles. The online server and standalone package of DeepATPseq are freely available at: https://jun-csbio.github.io/DeepATPseq/for academic use.

IT4SE-EP: Accurate Identification of Bacterial Type IV Secreted Effectors by Exploring Evolutionary Features from Two PSI-BLAST Profiles.

Many gram-negative bacteria use type IV secretion systems to deliver effector molecules to a wide range of target cells. These substrate proteins, which are called type IV secreted effectors (T4SE), manipulate host cell processes during infection, often resulting in severe diseases or even death of the host. Therefore, identification of putative T4SEs has become a very active research topic in bioinformatics due to its vital roles in understanding host-pathogen interactions. PSI-BLAST profiles have been experimentally validated to provide important and discriminatory evolutionary information for various protein classification tasks. In the present study, an accurate computational predictor termed iT4SE-EP was developed for identifying T4SEs by extracting evolutionary features from the position-specific scoring matrix and the position-specific frequency matrix profiles. First, four types of encoding strategies were designed to transform protein sequences into fixed-length feature vectors based on the two profiles. Then, the feature selection technique based on the random forest algorithm was utilized to reduce redundant or irrelevant features without much loss of information. Finally, the optimal features were input into a support vector machine classifier to carry out the prediction of T4SEs. Our experimental results demonstrated that iT4SE-EP outperformed most of existing methods based on the independent dataset test.

IDRBP-PPCT: Identifying Nucleic Acid-Binding Proteins Based on Position-Specific Score Matrix and Position-Specific Frequency Matrix Cross Transformation.

DNA-binding proteins (DBPs) and RNA-binding proteins (RBPs) are two important nucleic acid-binding proteins (NABPs), which play important roles in biological processes such as replication, translation and transcription of genetic material. Some proteins (DRBPs) bind to both DNA and RNA, also play a key role in gene expression. Identification of DBPs, RBPs and DRBPs is important to study protein-nucleic acid interactions. Computational methods are increasingly being proposed to automatically identify DNA- or RNA-binding proteins based only on protein sequences. One challenge is to design an effective protein representation method to convert protein sequences into fixed-dimension feature vectors. In this study, we proposed a novel protein representation method called Position-Specific Scoring Matrix (PSSM) and Position-Specific Frequency Matrix (PSFM) Cross Transformation (PPCT) to represent protein sequences. This method contains the evolutionary information in PSSM and PSFM, and their correlations. A new computational predictor called IDRBP-PPCT was proposed by combining PPCT and the two-layer framework based on the random forest algorithm to identify DBPs, RBPs and DRBPs. The experimental results on the independent dataset and the tomato genome proved the effectiveness of the proposed method. A user-friendly web-server of IDRBP-PPCT was constructed, which is freely available at http://bliulab.net/IDRBP-PPCT.

Protein-DNA Binding Residue Prediction via Bagging Strategy and Sequence-Based Cube-Format Feature.

Protein-DNA interactions play an important role in diverse biological processes. Accurately identifying protein-DNA binding residues is a critical but challenging task for protein function annotations and drug design. Although wet-lab experimental methods are the most accurate way to identify protein-DNA binding residues, they are time consuming and labor intensive. There is an urgent need to develop computational methods to rapidly and accurately predict protein-DNA binding residues. In this study, we propose a novel sequence-based method, named PredDBR, for predicting DNA-binding residues. In PredDBR, for each query protein, its position-specific frequency matrix (PSFM), predicted secondary structure (PSS), and predicted probabilities of ligand-binding residues (PPLBR) are first generated as three feature sources. Secondly, for each feature source, the sliding window technique is employed to extract the matrix-format feature of each residue. Then, we design two strategies, i.e., square root (SR) and average (AVE), to separately transform PSFM-based and two predicted feature source-based, i.e., PSS-based and PPLBR-based, matrix-format features of each residue into three corresponding cube-format features. Finally, after serially combining the three cube-format features, the ensemble classifier is generated via applying bagging strategy to multiple base classifiers built by the framework of 2D convolutional neural network. The computational experimental results demonstrate that the proposed PredDBR achieves an average overall accuracy of 93.7% and a Mathew's correlation coefficient of 0.405 on two independent validation datasets and outperforms several state-of-the-art sequenced-based protein-DNA binding residue predictors. The PredDBR web-server is available at https://jun-csbio.github.io/PredDBR/.

Protein Contact Map Prediction Based on ResNet and DenseNet

Residue-residue contact prediction has become an increasingly important tool for modeling the three-dimensional structure of a protein when no homologous structure is available. Ultradeep residual neural network (ResNet) has become the most popular method for making contact predictions because it captures the contextual information between residues. In this paper, we propose a novel deep neural network framework for contact prediction which combines ResNet and DenseNet. This framework uses 1D ResNet to process sequential features, and besides PSSM, SS3, and solvent accessibility, we have introduced a new feature, position-specific frequency matrix (PSFM), as an input. Using ResNet's residual module and identity mapping, it can effectively process sequential features after which the outer concatenation function is used for sequential and pairwise features. Prediction accuracy is improved following a final processing step using the dense connection of DenseNet. The prediction accuracy of the protein contact map shows that our method is more effective than other popular methods due to the new network architecture and the added feature input.

Protein Remote Homology Detection and Fold Recognition Based on Sequence-Order Frequency Matrix.

Protein remote homology detection and fold recognition are two critical tasks for the studies of protein structures and functions. Currently, the profile-based methods achieve the state-of-the-art performance in these fields. However, the widely used sequence profiles, like position-specific frequency matrix (PSFM) and position-specific scoring matrix (PSSM), ignore the sequence-order effects along protein sequence. In this study, we have proposed a novel profile, called sequence-order frequency matrix (SOFM), to extract the sequence-order information of neighboring residues from multiple sequence alignment (MSA). Combined with two profile feature extraction approaches, top-n-grams and the Smith-Waterman algorithm, the SOFMs are applied to protein remote homology detection and fold recognition, and two predictors called SOFM-Top and SOFM-SW are proposed. Experimental results show that SOFM contains more information content than other profiles, and these two predictors outperform other state-of-the-art methods. It is anticipated that SOFM will become a very useful profile in the studies of protein structures and functions.

PSFM-DBT: Identifying DNA-Binding Proteins by Combing Position Specific Frequency Matrix and Distance-Bigram Transformation.

DNA-binding proteins play crucial roles in various biological processes, such as DNA replication and repair, transcriptional regulation and many other biological activities associated with DNA. Experimental recognition techniques for DNA-binding proteins identification are both time consuming and expensive. Effective methods for identifying these proteins only based on protein sequences are highly required. The key for sequence-based methods is to effectively represent protein sequences. It has been reported by various previous studies that evolutionary information is crucial for DNA-binding protein identification. In this study, we employed four methods to extract the evolutionary information from Position Specific Frequency Matrix (PSFM), including Residue Probing Transformation (RPT), Evolutionary Difference Transformation (EDT), Distance-Bigram Transformation (DBT), and Trigram Transformation (TT). The PSFMs were converted into fixed length feature vectors by these four methods, and then respectively combined with Support Vector Machines (SVMs); four predictors for identifying these proteins were constructed, including PSFM-RPT, PSFM-EDT, PSFM-DBT, and PSFM-TT. Experimental results on a widely used benchmark dataset PDB1075 and an independent dataset PDB186 showed that these four methods achieved state-of-the-art-performance, and PSFM-DBT outperformed other existing methods in this field. For practical applications, a user-friendly webserver of PSFM-DBT was established, which is available at http://bioinformatics.hitsz.edu.cn/PSFM-DBT/.

FIMO: scanning for occurrences of a given motif

Summary: A motif is a short DNA or protein sequence that contributes to the biological function of the sequence in which it resides. Over the past several decades, many computational methods have been described for identifying, characterizing and searching with sequence motifs. Critical to nearly any motif-based sequence analysis pipeline is the ability to scan a sequence database for occurrences of a given motif described by a position-specific frequency matrix.Results: We describe Find Individual Motif Occurrences (FIMO), a software tool for scanning DNA or protein sequences with motifs described as position-specific scoring matrices. The program computes a log-likelihood ratio score for each position in a given sequence database, uses established dynamic programming methods to convert this score to a P-value and then applies false discovery rate analysis to estimate a q-value for each position in the given sequence. FIMO provides output in a variety of formats, including HTML, XML and several Santa Cruz Genome Browser formats. The program is efficient, allowing for the scanning of DNA sequences at a rate of 3.5 Mb/s on a single CPU.Availability and Implementation: FIMO is part of the MEME Suite software toolkit. A web server and source code are available at http://meme.sdsc.edu.Contact: t.bailey@imb.uq.edu.au; t.bailey@imb.uq.edu.auSupplementary information: Supplementary data are available at Bioinformatics online.

Moitf GibbsGA: Sampling Transcription Factor Binding Sites Coupled with PSFM Optimization by Genetic Algorithm

Identification of transcription factor binding sites (TFBSs) or motifs plays an important role in deciphering the mechanisms of gene regulation. Although many experimental and computational methods have been developed, finding TFBSs remains a challenging problem. We propose and develop a novel sampling based motif finding method coupled with PSFM optimization by genetic algorithm, which we call Motif GibbsGA. One significant feature of Motif GibbsGA is the combination of a Gibbs sampling method and a PSFM optimization by genetic algorithm. Based on position-specific frequency matrix (PSFM) motif model, a greedy strategy for choosing the initial parameters of PSFM is employed. Then a Gibbs sampler is build with respect to PSFM model. During the sampling process, PSFM is improved via a genetic algorithm. A post-processing with adaptive adding and removing is used to handle general cases with arbitrary numbers of instances per sequence. So Motif GibbsGA is capable of discovering several different motifs with differing numbers of occurrences in a single dataset. We test our method on the benchmark dataset compiled by Tompa et al. (2005) for assessing computational tools that predict TFBSs. The performance of Motif GibbsGA on this data set compares well to, and in many cases exceeds, the performance of existing tools. This is in part attributed to the significant role played by the genetic algorithm that improved PSFM.

Confidently Estimating the Number of DNA Replication Origins

We present a method for estimating and providing a confidence interval for the number of DNA replication origins in the genome of the yeast Kluyveromyces lactis. The method requires an initial set of verified sites from which a position specific frequency matrix (PSFM) can be constructed. We further assume that we have access to a sparingly used experimental procedure which can verify the functionality of a few, but not all, computationally predicted sites. While our motivation comes from estimating the number of autonomously replicating sequences (ARSs), our method can also be applied to estimating the genome-wide number of "functional" transcription factor binding sites, where functionality is determined by experimental verification of the transcription factor binding event using, for example, ChIP data. The reliability of our method is demonstrated by correctly predicting the known number of Saccharomyces cerevisiae ARSs as well as the number of S. cerevisiae probes that bind to the transcription factor ABF1.

A perspective of promoter architecture from the CCAAT box

The CCAAT box is an important promoter element regulated by NF-Y, a conserved trimer with histone-like features. We describe a new Position Specific Frequency Matrix (PSFM): we derived from 328 NF-Y promoters from the literature the p-CCAAT, and refined it by analysing ChIP on chip data (g-CCAAT). Interestingly, g-CCAAT- has distinct features, such as variations within the CCAAT pentanucleotide. We validated the NF-Y-dependency of several promoters with functional assays. We examined the presence of these PSFMs in all human promoters and detail a number of parameters of CCAAT boxes: position, orientation, distance from TSS, presence of TATA, CpG islands and enrichments of nearby TF elements. The CCAAT genes fall into different GO categories, with cell-cycle and chromatin/transcription specifically enriched. Additional findings surfaced: (i) the CCAAT-TATA combination, often mentioned in textbooks, is an exception, rather than the rule. CCAAT promoters are less precise in terms of TSS. (ii) There is a good correlation between CCAAT and CpG islands; (iii) selective TFs sites are enriched in CCAAT promoters, with precise stereoalignements of some of them. In conclusion, the new features of the CCAAT box and the link with the neighbouring elements will help in the functional classification of promoters.

GNBSL: A new integrative system to predict the subcellular location for Gram‐negative bacteria proteins

This paper proposes a new integrative system (GNBSL--Gram-negative bacteria subcellular localization) for subcellular localization specifized on the Gram-negative bacteria proteins. First, the system generates a position-specific frequency matrix (PSFM) and a position-specific scoring matrix (PSSM) for each protein sequence by searching the Swiss-Prot database. Then different features are extracted by four modules from the PSFM and the PSSM. The features include whole-sequence amino acid composition, N- and C-terminus amino acid composition, dipeptide composition, and segment composition. Four probabilistic neural network (PNN) classifiers are used to classify these modules. To further improve the performance, two modules trained by support vector machine (SVM) are added in this system. One module extracts the residue-couple distribution from the amino acid sequence and the other module applies a pairwise profile alignment kernel to measure the local similarity between every two sequences. Finally, an additional SVM is used to fuse the outputs from the six modules. Test on a benchmark dataset shows that the overall success rate of GNBSL is higher than those of PSORT-B, CELLO, and PSLpred. A web server GNBSL can be visited from http://166.111.24.5/webtools/GNBSL/index.htm.