iACVP-MR: Accurate Identification of Anti-coronavirus Peptide based on Multiple Features Information and Recurrent Neural Network.

BACKGROUND: Over the years, viruses have caused human illness and threatened human health. Therefore, it is pressing to develop anti-coronavirus infection drugs with clear function, low cost, and high safety. Anti-coronavirus peptide (ACVP) is a key therapeutic agent against coronavirus. Traditional methods for finding ACVP need a great deal of money and man power. Hence, it is a significant task to establish intelligent computational tools to able rapid, efficient and accurate identification of ACVP. METHODS: In this paper, we construct an excellent model named iACVP-MR to identify ACVP based on multiple features and recurrent neural networks. Multiple features are extracted by using reduced amino acid component and dipeptide component, compositions of k-spaced amino acid pairs, BLOSUM62 encoder according to the N5C5 sequence, as well as second-order moving average approach based on 16 physicochemical properties. Then, two recurrent neural networks named long-short term memory (LSTM) and bidirectional gated recurrent unit (BiGRU) combined attention mechanism are used for feature fusion and classification, respectively. RESULTS: The accuracies of ENNAVIA-C and ENNAVIA-D datasets under the 10-fold cross-validation are 99.15% and 98.92%, respectively, and other evaluation indexes have also obtained satisfactory results. The experimental results show that our model is superior to other existing models. CONCLUSION: The iACVP-MR model can be viewed as a powerful and intelligent tool for the accurate identification of ACVP. The datasets and source codes for iACVP-MR are freely downloaded at https://github.com/yunyunliang88/iACVP-MR.

AACFlow: an end-to-end model based on attention augmented convolutional neural network and flow-attention mechanism for identification of anticancer peptides.

MOTIVATION: Anticancer peptides (ACPs) have natural cationic properties and can act on the anionic cell membrane of cancer cells to kill cancer cells. Therefore, ACPs have become a potential anticancer drug with good research value and prospect. RESULTS: In this article, we propose AACFlow, an end-to-end model for identification of ACPs based on deep learning. End-to-end models have more room to automatically adjust according to the data, making the overall fit better and reducing error propagation. The combination of attention augmented convolutional neural network (AAConv) and multi-layer convolutional neural network (CNN) forms a deep representation learning module, which is used to obtain global and local information on the sequence. Based on the concept of flow network, multi-head flow-attention mechanism is introduced to mine the deep features of the sequence to improve the efficiency of the model. On the independent test dataset, the ACC, Sn, Sp, and AUC values of AACFlow are 83.9%, 83.0%, 84.8%, and 0.892, respectively, which are 4.9%, 1.5%, 8.0%, and 0.016 higher than those of the baseline model. The MCC value is 67.85%. In addition, we visualize the features extracted by each module to enhance the interpretability of the model. Various experiments show that our model is more competitive in predicting ACPs.

EACVP: An ESM-2 LM Framework Combined CNN and CBAM Attention to Predict Anti-coronavirus Peptides.

BACKGROUND: The novel coronavirus pneumonia (COVID-19) outbreak in late 2019 killed millions worldwide. Coronaviruses cause diseases such as severe acute respiratory syndrome (SARS-Cov) and SARS-COV-2. Many peptides in the host defense system have antiviral activity. How to establish a set of efficient models to identify anti-coronavirus peptides is a meaningful study. METHODS: Given this, a new prediction model EACVP is proposed. This model uses the evolutionary scale language model (ESM-2 LM) to characterize peptide sequence information. The ESM model is a natural language processing model trained by machine learning technology. It is trained on a highly diverse and dense dataset (UR50/D 2021_04) and uses the pre-trained language model to obtain peptide sequence features with 320 dimensions. Compared with traditional feature extraction methods, the information represented by ESM-2 LM is more comprehensive and stable. Then, the features are input into the convolutional neural network (CNN), and the convolutional block attention module (CBAM) lightweight attention module is used to perform attention operations on CNN in space dimension and channel dimension. To verify the rationality of the model structure, we performed ablation experiments on the benchmark and independent test datasets. We compared the EACVP with existing methods on the independent test dataset. RESULTS: Experimental results show that ACC, F1-score, and MCC are 3.95%, 35.65% and 0.0725 higher than the most advanced methods, respectively. At the same time, we tested EACVP on ENNAVIA-C and ENNAVIA-D data sets, and the results showed that EACVP has good migration and is a powerful tool for predicting anti-coronavirus peptides. CONCLUSION: The results prove that this model EACVP could fully characterize the peptide information and achieve high prediction accuracy. It can be generalized to different data sets. The data and code of the article have been uploaded to https://github.- com/JYY625/EACVP.git.

TMSC-m7G: A transformer architecture based on multi-sense-scaled embedding features and convolutional neural network to identify RNA N7-methylguanosine sites.

RNA N7-methylguanosine (m7G) is a crucial chemical modification of RNA molecules, whose principal duty is to maintain RNA function and protein translation. Studying and predicting RNA N7-methylguanosine sites aid in comprehending the biological function of RNA and the development of new drug therapy regimens. In the present scenario, the efficacy of techniques, specifically deep learning and machine learning, stands out in the prediction of RNA N7-methylguanosine sites, leading to improved accuracy and identification efficiency. In this study, we propose a model leveraging the transformer framework that integrates natural language processing and deep learning to predict m7G sites, called TMSC-m7G. In TMSC-m7G, a combination of multi-sense-scaled token embedding and fixed-position embedding is used to replace traditional word embedding for the extraction of contextual information from sequences. Moreover, a convolutional layer is added in the encoder to make up for the shortage of local information acquisition in transformer. The model's robustness and generalization are validated through 10-fold cross-validation and an independent dataset test. Results demonstrate outstanding performance in comparison to the most advanced models available. Among them, the Accuracy of TMSC-m7G reaches 98.70% and 92.92% on the benchmark dataset and independent dataset, respectively. To facilitate the popularization and use of the model, we have developed an intuitive online prediction tool, which is easily accessible for free at http://39.105.212.81/.

iAVPs-ResBi: Identifying antiviral peptides by using deep residual network and bidirectional gated recurrent unit.

Human history is also the history of the fight against viral diseases. From the eradication of viruses to coexistence, advances in biomedicine have led to a more objective understanding of viruses and a corresponding increase in the tools and methods to combat them. More recently, antiviral peptides (AVPs) have been discovered, which due to their superior advantages, have achieved great impact as antiviral drugs. Therefore, it is very necessary to develop a prediction model to accurately identify AVPs. In this paper, we develop the iAVPs-ResBi model using k-spaced amino acid pairs (KSAAP), encoding based on grouped weight (EBGW), enhanced grouped amino acid composition (EGAAC) based on the N5C5 sequence, composition, transition and distribution (CTD) based on physicochemical properties for multi-feature extraction. Then we adopt bidirectional long short-term memory (BiLSTM) to fuse features for obtaining the most differentiated information from multiple original feature sets. Finally, the deep model is built by combining improved residual network and bidirectional gated recurrent unit (BiGRU) to perform classification. The results obtained are better than those of the existing methods, and the accuracies are 95.07, 98.07, 94.29 and 97.50% on the four datasets, which show that iAVPs-ResBi can be used as an effective tool for the identification of antiviral peptides. The datasets and codes are freely available at https://github.com/yunyunliang88/iAVPs-ResBi.

Hexapartite steering based on a four-wave-mixing process with a spatially structured pump.

Multipartite Einstein-Podolsky-Rosen (EPR) steering has been widely studied, for realizing safer quantum communication. The steering properties of six spatially separated beams from the four-wave-mixing process with a spatially structured pump are investigated. Behaviors of all (1+i)/(i+1)-mode (i=1,2,3) steerings are understandable, if the role of the corresponding relative interaction strengths are taken into account. Moreover, stronger collective multipartite steerings including five modes can be obtained in our scheme, which has potential applications in ultra-secure multiuser quantum networks when the issue of trust is critical. By further discussing about all monogamy relations, it is noticed that the type-IV monogamy relations, which are naturally included in our model, are conditionally satisfied. Matrix representation is used to express the steerings for the first time, which is very useful to understand the monogamy relations intuitively. Different steering properties obtained in this compact phase-insensitive scheme have potential applications for different kinds of quantum communication tasks.

Fibroblast exosomal TFAP2C induced by chitosan oligosaccharides promotes peripheral axon regeneration via the miR-132-5p/CAMKK1 axis.

Chitosan and its degradation product, oligosaccharides, have been shown to facilitate peripheral nerve regeneration. However, the underlying mechanisms are not well understood. In this study, we analyzed the protein expression profiles in sciatic nerves after injury using proteomics. A group of proteins related to exosome packaging and transport is up-regulated by chitosan oligosaccharides (COS), implying that exosomes are involved in COS-induced peripheral nerve regeneration. In fact, exosomes derived from fibroblasts (f-EXOs) treated with COS significantly promoted axon extension and regeneration. Exosomal protein identification and functional studies, revealed that TFAP2C is a key factor in neurite outgrowth induced by COS-f-EXOs. Furthermore, we showed that TFAP2C targets the pri-miRNA-132 gene and represses miR-132-5p expression in dorsal root ganglion neurons. Camkk1 is a downstream substrate of miR-132-5p that positively affects axon extension. In rats, miR-132-5p antagomir stimulates CAMKK1 expression and improves axon regeneration and functional recovery in sciatic nerves after injury. Our data reveal the mechanism for COS in axon regeneration, that is COS induce fibroblasts to produce TFAP2C-enriched EXOs, which are then transferred into axons to promote axon regeneration via miR-132-5p/CAMKK1. Moreover, these results show a new facet of fibroblasts in axon regeneration in peripheral nerves.

Identification of DNA N4-methylcytosine sites based on multi-source features and gradient boosting decision tree.

N4-methylcytosine (4 mC) is an important and common methylation which widely exists in prokaryotes. It plays a crucial role in correcting DNA replication errors and protecting host DNA against degradation by restrictive enzymes. Hence, the accurate identification for 4 mC sites is greatly significant for understanding biological functions and treating gene diseases. In this paper, a novel model is designed for identifying 4 mC sites. Firstly, we extract features from original sequences by multi-source feature representation methods, which are mono-nucleotide binary and k-mer frequency, dinucleotide binary and position-specific frequency, ring-function-hydrogen-chemical properties, dinucleotide-based DNA properties and trinucleotide-based DNA properties. Subsequently, gradient boosting decision tree is applied to select the optimal feature set and remove redundant information. Finally, support vector machine is employed to predict 4 mC or non-4mC sites. The accuracies of six datasets reach 0.851, 0.859, 0.801, 0.87, 0.859 and 0.901, respectively, which are superior to previous prediction methods. Therefore, the results show that our predictor is a feasible and effective tool for identifying 4 mC sites. Furthermore, an online web server is established at http://dnan4c.zhanglab.site.

Data driven adaptive Gaussian mixture model for solving Fokker-Planck equation.

The Fokker-Planck (FP) equation provides a powerful tool for describing the state transition probability density function of complex dynamical systems governed by stochastic differential equations (SDEs). Unfortunately, the analytical solution of the FP equation can be found in very few special cases. Therefore, it has become an interest to find a numerical approximation method of the FP equation suitable for a wider range of nonlinear systems. In this paper, a machine learning method based on an adaptive Gaussian mixture model (AGMM) is proposed to deal with the general FP equations. Compared with previous numerical discretization methods, the proposed method seamlessly integrates data and mathematical models. The prior knowledge generated by the assumed mathematical model can improve the performance of the learning algorithm. Also, it yields more interpretability for machine learning methods. Numerical examples for one-dimensional and two-dimensional SDEs with one and/or two noises are given. The simulation results show the effectiveness and robustness of the AGMM technique for solving the FP equation. In addition, the computational complexity and the optimization algorithm of the model are also discussed.

Estimation of critical closing pressure using intravascular blood pressure of the common carotid artery.

PURPOSE: Radial artery, femoral artery, and aortic arterial blood pressures (ABPs) can be used to estimate cerebral critical closing pressure (CrCP) and resistance-area product (RAP). However, the use of the common carotid artery (CCA) intravascular blood pressure to estimate CrCP is unclear. Thus, using continuous ABP monitoring, we compared the CrCP and RAP estimated from CCA measurements with the corresponding values acquired from the radial artery. METHODS: In this retrospective cross-sectional study, we analyzed CrCP and RAP estimations from 21 patients with normal cerebral blood vessels between July 23, 2010, and February 9, 2011, using linear regression of the cerebral blood flow velocity-ABP relationship. RESULTS: Bland-Altman analysis showed that the average differences (95% limits of agreement) between the radial artery and the left CCA were -6.3 (-53.1 - 40.6) mmHg and -0.08 (-0.41 - 0.25) mmHg s cm-1 for CrCP and RAP, respectively. CONCLUSIONS: The CrCP and RAP estimated from the CCA measurements are consistent with the corresponding values obtained from the radial artery.

Exosomal miR-673-5p from fibroblasts promotes Schwann cell-mediated peripheral neuron myelination by targeting the TSC2/mTORC1/SREBP2 axis.

Peripheral myelination is a complicated process, wherein Schwann cells (SCs) promote the formation of the myelin sheath around the axons of peripheral neurons. Fibroblasts are the second resident cells in the peripheral nerves; however, the precise function of fibroblasts in SC-mediated myelination has rarely been examined. Here, we show that exosomes derived from fibroblasts boost myelination-related gene expression in SCs. We used exosome sequencing, together with bioinformatic analysis, to demonstrate that exosomal microRNA miR-673-5p is capable of stimulating myelin gene expression in SCs. Subsequent functional studies revealed that miR-673-5p targets the regulator of mechanistic target of the rapamycin (mTOR) complex 1 (mTORC1) tuberous sclerosis complex 2 in SCs, leading to the activation of downstream signaling pathways including mTORC1 and sterol-regulatory element binding protein 2. In vivo experiments further confirmed that miR-673-5p activates the tuberous sclerosis complex 2/mTORC1/sterol-regulatory element binding protein 2 axis, thus promoting the synthesis of cholesterol and related lipids and subsequently accelerating myelin sheath maturation in peripheral nerves. Overall, our findings revealed exosome-mediated cross talk between fibroblasts and SCs that plays a pivotal role in peripheral myelination. We propose that exosomes derived from fibroblasts and miR-673-5p might be useful for promoting peripheral myelination in translational medicine.

M6A-GSMS: Computational identification of N6-methyladenosine sites with GBDT and stacking learning in multiple species.

N6-methyladenosine (m6A) is one of the most abundant forms of RNA methylation modifications currently known. It involves a wide range of biological processes, including degradation, stability, alternative splicing, etc. Therefore, the development of convenient and efficient m6A prediction technologies are urgent. In this work, a novel predictor based on GBDT and stacking learning is developed to identify m6A sites, which is called M6A-GSMS. To achieve accurate prediction, we explore RNA sequence information from four aspects: correlation, structure, physicochemical properties and pseudo ribonucleic acid composition. After using the GBDT algorithm for feature selection, a stacking model is constructed by combining seven basic classifiers. Compared with other state-of-the-art methods, the results show that M6A-GSMS can obtain excellent performance for identifying the m6A sites. The prediction accuracy of A.thaliana, D.melanogaster, M.musculus, S.cerevisiae and Human reaches 88.4%, 60.8%, 80.5%, 92.4% and 61.8%, respectively. This method provides an effective prediction for the investigation of m6A sites. In addition, all the datasets and codes are currently available at https://github.com/Wang-Jinyue/M6A-GSMS.Communicated by Ramaswamy H. Sarma.

iEnhancer-MFGBDT: Identifying enhancers and their strength by fusing multiple features and gradient boosting decision tree.

Enhancer is a non-coding DNA fragment that can be bound with proteins to activate transcription of a gene, hence play an important role in regulating gene expression. Enhancer identification is very challenging and more complicated than other genetic factors due to their position variation and free scattering. In addition, it has been proved that genetic variation in enhancers is related to human diseases. Therefore, identification of enhancers and their strength has important biological meaning. In this paper, a novel model named iEnhancer-MFGBDT is developed to identify enhancer and their strength by fusing multiple features and gradient boosting decision tree (GBDT). Multiple features include k-mer and reverse complement k-mer nucleotide composition based on DNA sequence, and second-order moving average, normalized Moreau-Broto auto-cross correlation and Moran auto-cross correlation based on dinucleotide physical structural property matrix. Then we use GBDT to select features and perform classification successively. The accuracies reach 78.67% and 66.04% for identifying enhancers and their strength on the benchmark dataset, respectively. Compared with other models, the results show that our model is useful and effective intelligent tool to identify enhancers and their strength, of which the datasets and source codes are available at https://github.com/shengli0201/iEnhancer-MFGBDT1.

The Influence of the Surface Topographical Cues of Biomaterials on Nerve Cells in Peripheral Nerve Regeneration: A Review.

The surface topographies of artificial implants including surface roughness, surface groove size and orientation, and surface pore size and distribution have a great influence on the adhesion, migration, proliferation, and differentiation of nerve cells in the nerve regeneration process. Optimizing the surface topographies of biomaterials can be a key strategy for achieving excellent cell performance in various applications such as nerve tissue engineering. In this review, we offer a comprehensive summary of the surface topographies of nerve implants and their effects on nerve cell behavior. This review also emphasizes the latest work progress of the layered structure of the natural extracellular matrix that can be imitated by the material surface topology. Finally, the future development of surface topographies on nerve regeneration was prospectively remarked.

iPromoter-ET: Identifying promoters and their strength by extremely randomized trees-based feature selection.

Promoter is a region of DNA that determines the transcription of a particular gene. There are several σ factors in the RNA polymerase, which has the function of identifying the promoter and facilitating the binding of the RNA polymerase to the promoter. Owing to the importance of promoter in genome research, it is an urgent task to develop computational tool for effectively identifying promoters and their strength facing the avalanche of DNA sequences discovered in the post-genomic age. In this paper, we develop a model named iPromoter-ET using the k-mer nucleotide composition, binary encoding and dinucleotide property matrix-based distance transformation for features extraction, and extremely randomized trees (extra trees) for feature selection. Its 1st layer is used to identify whether a DNA sequence is of promoter or not, while its 2nd layer is to identify promoter samples as being strong or weak promoter. Support vector machine and the five cross-validation are used to perform identification and assess performance, respectively. The results indicate that our model remarkably outperforms the existing models in both the 1st and 2nd layers for accuracy and stability. We anticipate that our proposed model will become a very effective intelligent tool, or at the least, a complementary tool to the existing modes of identifying promoters and their strength. Moreover, the datasets and codes for iPromoter-ET are freely available at https://github.com/shengli0201/iPromoter-ET.

Proteomic Analysis of Silk Fibroin Reveals Diverse Biological Function of Different Degumming Processing From Different Origin.

Silk, as a kind of natural fibrin, has been prepared into various biomaterials due to its excellent biocompatibility and mechanicalness. However, there are some controversies on the biocompatibility of silk fibroin (SF), especially when it coexists with sericin. In this study, two kinds of silk from Jiangsu and Zhejiang were degummed with two concentrations of Na2CO3 solution, respectively, to obtain four kinds of silk fibroin. The effects of different degumming treatments on silk fibroin properties were analyzed by means of color reaction, apparent viscosity measurement, and transmission electron microscope and isobaric tags for relative and absolute quantification analyses, and the effects of different silk fibroin membranes on the growth of Schwann cells were evaluated. The results showed that the natural silk from Zhejiang treated with 0.05% Na2CO3 solution had a fuller structure, higher apparent viscosity, and better protein composition. While SF obtained by degumming with 0.5% Na2CO3 solution was more beneficial to cell adhesion and proliferation due to the thorough removal of sericin. This study may provide important theoretical and experimental bases for the selection of biomaterials for fabricating artificial nerve grafts.

Application of Machine Learning Techniques in Drug-target Interactions Prediction.

BACKGROUND: Drug-Target interactions are vital for drug design and drug repositioning. However, traditional lab experiments are both expensive and time-consuming. Various computational methods which applied machine learning techniques performed efficiently and effectively in the field. RESULTS: The machine learning methods can be divided into three categories basically: Supervised methods, Semi-Supervised methods and Unsupervised methods. We reviewed recent representative methods applying machine learning techniques of each category in DTIs and summarized a brief list of databases frequently used in drug discovery. In addition, we compared the advantages and limitations of these methods in each category. CONCLUSION: Every prediction model has both strengths and weaknesses and should be adopted in proper ways. Three major problems in DTIs prediction including the lack of nonreactive drug-target pairs data sets, over optimistic results due to the biases and the exploiting of regression models on DTIs prediction should be seriously considered.

Application of conductive PPy/SF composite scaffold and electrical stimulation for neural tissue engineering.

Electrical stimulation (ES) with conductive polymers can dramatically enhance neurite outgrowth and promote neural regeneration. However, besides ES, the practical applications of neural repair is also highly dependent on the nerve cell functionality and response to substrate conductivity. Therefore, the combination of the ES and suitable materials, such as tissue scaffolds, has been applied to facilitate treatment of neural injuries and demonstrated great potential in peripheral nerve regeneration. In this study, polypyrrole/silk fibroin (PPy/SF) conductive composite scaffold was fabricated by 3D bioprinting and electrospinning. Schwann cells seeded on these scaffolds were electrically stimulated and hence demonstrated enhanced viability, proliferation and migration, as well as upregulated expression of neurotrophic factors. Furthermore, the constructed PPy/SF conductive nerve guidance conduits accompanying with ES could effectively promote axonal regeneration and remyelination in vivo. Moreover, we found that the MAPKs signal transduction pathway was activated by ES at the conductive conduit. Our findings demonstrate that the PPy/SF conductive composite scaffolds with longitudinal guidance exhibit favorable properties for clinical use and promotes nerve regeneration and functional recovery.

Identifying DNase I hypersensitive sites using multi-features fusion and F-score features selection via Chou's 5-steps rule.

DNase I hypersensitive sites (DHSs) are regarded as those regions of chromatin that are sensitive to cleavage by the DNase I enzyme. Identification of DNase I hypersensitive sites will provide useful insights for discovering DNA's functional elements from the non-coding sequences in the biomedical research. Because of the significance for DNase I hypersensitive sites, it is indispensable to develop an accurate, fast, robust, and high-throughput automated computational model. In this paper, we develop a model named iDHSs-MFF by combining multiple fusion features and F-score features selection approach. The multiple fusion features include three auto-correlation descriptors based on the dinucleotide property matrix and the trinucleotide property matrix (TPM), Pseudo-DPM and Pseudo-TPM. Evaluation by the jackknife cross-validation indicates that the selected features by F-score are effective in the identification of DNase I hypersensitive sites. Experimental results on two benchmark datasets demonstrate that the proposed model outperforms some highly related models. Systematic application of this computational approach will greatly facilitate the analysis of transcriptional regulatory elements. The datasets and Matlab source codes are freely available at: https://github.com/shengli0201/Datasets.

Modulation of myelin formation by combined high affinity with extracellular matrix structure of electrospun silk fibroin nanoscaffolds.

Remyelination is a major therapeutic goal in peripheral nerve regeneration, serving to restore function of demyelinated axons and provide neuroprotection. In order to apply myelin biogenesis strategies to peripheral nerve defects, the tissue engineered substitutes might be amenable to the promotion of this repair process. Electrospun nanofibers are considered as promising scaffolds for tissue engineering due to extracellular matrix mimicking factor and enhanced electrostatic interaction resulting in a controllable 3 D nanofibrous membrane. In order to explore the role of electrospun silk fibroin (SF) membrane in myelination, co-culture of dorsal root ganglion (DRG) neurons and Schwann cells (SCs) in vitro was established and observed. Scanning electron microscopy was used to observe DRG adhesion to the membranes, the electrospinning SF membrane is more favorable to the adhesion of DRG. The immunofluorescence staining of MAG and NF showed considerable amount of myelin were formed, and the myelin was tightly wrapped around the axons of the neurons, which was confirmed under the scanning electron microscope observation. Real-time quantitative PCR technique was used to determine the gene expression level of DRG neurons cultured at different time points. The results showed that the mRNA levels of N-cadherin, laminin, fibronectin were higher than those in the control group. Our results showed that the electrospun SF nanofibers can provide topographical and chemical cues that mimic (to a certain extent) the extracellular matrix.