Reconstructing precise CAD modeling sequences from point clouds remains a challenging task, especially for objects with complex geometry and topology. In this paper, by formulating the CAD sequence reconstruction as a Markov decision process, we introduce ReACT, a novel Reward-informed Autoregressive decision Cad Transformer architecture for robust CAD sequence prediction. Beyond previous imitation-only approaches, our key innovation is to frame the CAD Transformer under a reinforcement learning paradigm and thereby integrate reward-inspired heuristic learning into our architecture. This allows ReACT to effectively leverage shape-aware long-term reward feedback to guide the inference of (nearly) optimal CAD commands. Specifically, conditioned on past tokens, comprising the historical CAD states, sketch-extrude commands (i.e., actions) and associated geometric rewards, ReACT autoregressively outputs the most promising CAD commands in a causal manner. In particular, we develop a novel scaffold-aware CAD state representation that integrates global point-command features with an incrementally constructed surface point scaffold, enabling fine-grained geometric reasoning for subsequent reconstruction prediction. Moreover, an effective local barrel points-guided dense reward function is designed to jointly evaluate surface fidelity and command efficiency for reliable reward guidance. Extensive evaluations on the DeepCAD and Fusion360 benchmarks demonstrate that ReACT can achieve superior CAD reconstruction quality, even for objects with complex shapes.

Generative recommendation (GR) is an emerging paradigm that tokenizes items into discrete tokens and learns to autoregressively generate the next tokens as predictions. While this token-generation paradigm is expected to surpass traditional transductive methods, potentially generating new items directly based on semantics, we empirically show that GR models predominantly generate items seen during training and struggle to recommend unseen items. In this paper, we propose SpecGR, a plug-and-play framework that enables GR models to recommend new items in an inductive setting. SpecGR uses a drafter model with inductive capability to propose candidate items, which may include both existing items and new items. The GR model then acts as a verifier, accepting or rejecting candidates while retaining its strong ranking capabilities. We further introduce the guided re-drafting technique to make the proposed candidates more aligned with the outputs of generative recommendation models, improving the verification efficiency. We consider two variants for drafting: (1) using an auxiliary drafter model for better flexibility, or (2) leveraging the GR model's own encoder for parameter-efficient self-drafting. Extensive experiments on three real-world datasets demonstrate that SpecGR exhibits both strong inductive recommendation ability and the best overall performance among the compared methods.

Semantic IDs (SIDs) are hierarchical item identifiers learned via residual quantization, offering a promising solution to cold-start recommendation, yet their integration into discriminative recommendations remains challenging and lacks systematic investigation. We present Pin-SCALE, a framework for optimized end-to-end integration of SID into dense retrieval in cascading recommender systems. Pin-SCALE instantiates the principles through three technical contributions: (1) cascading pooling preserving residual quantization hierarchy that outperforms common pooling schema and attention;(2) engagement-aware tokenization that encodes collaborative signals to fully utilize both content and user engagement pattern; and (3) multi-view contrastive learning that harnesses query-item and item-item co-occurrence to align SID representations with engagement prediction. Through extensive offline analyses, we collected systematic guidance and proved the effectiveness of Pin-SCALE. Furthermore, the framework has been tested online on multiple surfaces at Pinterest including Closeup, Home Feed and Search, with different content types like organic and e-commerce. Pin-SCALE achieves substantial improvements in fresh engagements (+3.67% repins) as well as platform-level retention (+0.05% DAU). Our work has been shipped into production to serve billions of requests daily and drive discovery journey of our users, as well as provides principled guidelines for SID adoption in discriminative recommendation models at production scale.

MOTIVATION: Enhancer-promoter interactions (EPIs) are essential for gene regulation and disease progression. Recent studies have shown that distal enhancers can regulate target genes through interactions with nearby promoters, providing important insights into transcriptional regulation mechanisms. Although high-throughput experimental techniques have enabled large-scale identification of EPIs, these methods are often costly and time-consuming. In addition, existing computational approaches still face challenges in effectively integrating heterogeneous feature representations from different cell lines. RESULTS: We propose a stacked ensemble framework for EPI prediction that integrates feature representations from diverse cell line datasets using multiple machine learning algorithms. The extracted complementary patterns are further combined by an XGBoost classifier to improve robustness against overfitting. Experiments on six independent datasets show that the proposed method achieves superior accuracy and generalization compared with existing EPI prediction models, with an average AUROC of 0.909 while maintaining computational efficiency. AVAILABILITY: The source code and its archived release are available at GitHub and Zenodo. The Zenodo archive provides a versioned snapshot of the repository: https://zenodo.org/records/19952998.

Anticancer peptides (ACPs) are short bioactive sequences that selectively target tumor cells with minimal toxicity, positioning them as promising candidates for next-generation cancer therapies. However, existing computational models face limitations in sequence representation and class imbalance. To address these challenges, we propose UACD-ACPs, a unified fusion-driven framework that integrates a diffusion-inspired noise-conditioned classifier for ACP prediction and a diffusion-based peptide generation module with cancer-type-aware organization for targeted downstream screening. The classification module integrates ProtBERT-based semantic embeddings with physicochemical descriptors via the Multiscale Embedding Compression Strategy (MECS) and a diffusion-inspired noise-conditioned encoder, substantially enhancing predictive robustness and accuracy, particularly under challenging imbalanced multi-class settings. In the generative pipeline, we introduce a denoising diffusion-based generative framework augmented by two novel fusion modules: the Bitemporal Fusion Module (BFM) and the Temporal Feature Attention Module (TFAM). These modules perform multi-scale temporal and semantic fusion to promote the generation of structurally coherent and functionally relevant peptide candidates. Experimental results demonstrate that UACD-ACPs outperforms state-of-the-art methods in terms of accuracy, F1-score, and AUC-ROC. The generated peptides exhibit favorable physicochemical properties, diverse secondary structures, and strong structural stability, as validated by molecular dynamics simulations and membrane-binding analyses. Overall, this study highlights the potential of fusion-driven diffusion-based frameworks for alleviating class imbalance and data heterogeneity in anticancer peptide modeling, paving the way for scalable and biologically grounded ACP discovery.

This paper presents PartCAD, a novel framework for reconstructing CAD modeling sequences directly from point clouds by projection-guided, part-aware geometry reasoning. It consists of (1) an autoregressive approach that decomposes point clouds into part-aware latent representations, serving as interpretable anchors for CAD generation; (2) a projection guidance module that provides explicit cues about underlying design intent via triplane projections; and (3) a non-autoregressive decoder to generate sketch-extrusion parameters in a single forward pass, enabling efficient and structurally coherent CAD instruction synthesis. By bridging geometric signals and semantic understanding, PartCAD tackles the challenge of reconstructing editable CAD models—capturing underlying design processes—from 3D point clouds. Extensive experiments show that PartCAD significantly outperforms existing methods for CAD instruction generation in both accuracy and robustness. The work sheds light on part-driven reconstruction of interpretable CAD models, opening new avenues in reverse engineering and CAD automation.

Predicting drug–drug interactions (DDIs) is crucial for understanding and preventing adverse drug reactions (ADRs). However, most existing methods inadequately explore the interactive information between drugs in a self-supervised manner, limiting our comprehension of drug–drug associations. This paper introduces EDDINet : E nhancing D rug- D rug I nteraction Prediction via Information Flow and Consensus-Constrained Multi-Graph Contrastive Learning for precise DDI prediction. We first present a cross-modal information-flow mechanism to integrate diverse drug features, enriching the structural insights conveyed by the drug feature vector. Next, we employ contrastive learning to filter various biological networks, enhancing the model’s robustness. Additionally, we propose a consensus regularization framework that collaboratively trains multi-view models, producing high-quality drug representations. To unify drug representations derived from different biological information, we utilize an attention mechanism for DDI prediction. Extensive experiments demonstrate that EDDINet surpasses state-of-the-art unsupervised models and outperforms some supervised baseline models in DDI prediction tasks. Our approach shows significant advantages and holds promising potential for advancing DDI research and improving drug safety assessments. Our codes are available at: https://github.com/95LY/EDDINet_code . • EDDINet is proposed via Information Flow and Consensus-Constrained Multi-Graph Contrastive Learning. • Introduce the cross-modal information-flow mechanism to facilitate the information across various drug features. • EDDINet surpasses state-of-the-art unsupervised models and even outperforms some supervised baseline models in DDI prediction tasks.

MOTIVATION: Enhancers and promoters, as regulatory DNA elements, play pivotal roles in gene expression, homeostasis, and disease development across various biological processes. With advancing research, it has been uncovered that distal enhancers may engage with nearby promoters to modulate the expression of target genes. This discovery holds significant implications for deepening our comprehension of various biological mechanisms. In recent years, numerous high-throughput wet-lab techniques have been created to detect possible interactions between enhancers and promoters. However, these experimental methods are often time-intensive and costly. RESULTS: To tackle this issue, we have created an innovative deep learning approach, EPIPDLF, which utilizes advanced deep learning techniques to predict EPIs based solely on genomic sequences in an interpretable manner. Comparative evaluations across six benchmark datasets demonstrate that EPIPDLF consistently exhibits superior performance in EPI prediction. Additionally, by incorporating interpretable analysis mechanisms, our model enables the elucidation of learned features, aiding in the identification and biological analysis of important sequences. AVAILABILITY AND IMPLEMENTATION: The source code and data are available at: https://github.com/xzc196/EPIPDLF.

N6-methyladenosine (m6A) can significantly affect RNA expression, gene regulation, and determination of cell fate. As a common and abundant post-transcriptional modification (PTM) of RNA, m6A is also closely associated with the occurrence of numerous diseases. Thus, identifying the m6A modification site in the RNA sequence is a prerequisite for related research. High-throughput sequencing technology has high requirements and low cost performance. Computational methods have made encouraging progress in site prediction. However, most models only consider the effects of different species, ignoring the simultaneous exploration of RNA modifications in different tissues within the same species. We develop and validate a fuzzy system based on Block Sparse Bayesian Learning (BSBL), named BSBL-TSK-FS, which is a powerful sequence-level m6A prediction model. We introduce a Bayesian method that provides a posterior probability output to produce more sparse solutions so that the model has higher accuracy. The model classifies the m6A sites in several tissues of mouse, human, and rat. Under the five-fold cross-validation method (5-CV), the precision of the BSBL-TSK-FS model is 0.84∼0.95. The accuracy of our model improves by 9.4% over the existing SOTA predictors. BSBL-TSK-FS achieves superior performance over current SOTA methods. Finally, in order to verify the generalizability of the model, we carry out cross-species tests, and the results prove the robustness and adaptability of the model. An accurate and reliable sequence modification prediction model is developed to better understand the complex landscape of methylation modification.

Therapeutic peptides play a key role in regulating cellular functions and repairing damaged cells through targeted molecular interactions. Traditional wet-lab methods for identifying therapeutic peptides rely on time-consuming biochemical assays and low-throughput screening techniques, which struggle to capture complex sequence-stability relationships critical for drug development. To address these limitations, we innovatively integrate a pretrained protein language model with stacked bidirectional long short-term memory (BiLSTM) encoders. This hybrid architecture enables hierarchical extraction of both global contextual patterns (via the language model) and localized sequential dependencies (via BiLSTM), effectively modeling nonlinear correlations within peptide sequences. A key technical lies in the proposed kernelized Takagi-Sugeno-Kang fuzzy system (K-TSK-FS), which combines fuzzy logic with kernel methods to handle sequence ambiguity while maintaining interpretability. Unlike conventional classifiers, this system maps high-dimensional features into a reproducing kernel Hilbert space, enhancing discrimination between therapeutic and non-therapeutic peptides through nonlinear decision boundaries. To evaluate the model, six benchmark datasets are used to test our model. Experimental results show that our method achieves better prediction performance.

In recent years, numerous studies have demonstrated a close connection between human diseases and the regulation of non-coding RNAs (ncRNAs). Predicting potential ncRNAs associated with disease can help provide critical information for diagnosis and treatment of disease, leading to better disease analysis and prevention. Building good algorithms for predicting associations between ncRNAs and disease is critical. Many current algorithms have poor performance in identifying the association between ncRNAs and diseases. As a method for predicting the association between ncRNAs and diseases, we develop a Matrix Factorization method based on the Correntropy Induced Loss (C-loss) function (C-lossMF). In our model, we first construct ncRNA similarity matrix and disease similarity matrix by considering some important similarity information, and extract effective information of ncRNA and disease from them. Next, we perform matrix decomposition of ncRNA-disease association matrix and apply $L2$ loss and C-loss. Then we add collaborative regularization of RNA similarity matrix and the collaborative regularization of disease similarity matrix to take full advantage of the information in the similarity matrix. In particular, we propose a method that combines semi-quadratic optimization and gradient descent to optimize the model. In the experiments, we utilize the five-fold cross validation method on four datasets to evaluate the performance of C-lossMF. Comparing this model with other advanced models, the results show that it performs better.

In many biological processes, N6-methyladenosine (m6A) plays a critical role. Experimental methods for identifying m6A sites have proven to be costly, and existing computational methods still require improvement. To address these challenges, we develop a novel computational method called structured sparse regularization-based fuzzy hierarchical echo state network to identify m6A sites in mammals. We apply fuzzy systems to deep learning. Compared with traditional fuzzy inference systems, this deep fuzzy network has the ability to generate feature representations. Echo state network (ESN) is a special type of recurrent neural network, which consists of an input layer, a randomly generated large fixed hidden layer (called a reservoir), and an adaptive output layer. The advantages of our method over ESNs are that it is capable of mining and capturing hidden features layer-by-layer within reservoirs and has better approximation performance. In order to remove redundancy, the output layer weights are trained by structured sparse learning, which enhances the generalizability and robustness of the method. Evaluation of our method by testing it on tissue-specific datasets shows that it outperforms existing tools.

Hyperspectral Image (HSI) classification, which aims to assign pixel-level categories for given HSI data, has achieved remarkable success with deep learning architectures. However, such approaches typically require large amounts of annotated data, which are often scarce in practical applications. To address the challenge of limited annotated samples, this paper proposes a novel framework that leverages both semantic and structural prior knowledge to extract more expressive HSI features. This paper proposes a Dual-Branch Hypergraph Convolutional Network (DB-HGCN) for comprehensive spectral-spatial-semantic feature extraction, which employs multi-hop constrained superpixel-level hypergraphs to effectively model the complex high-order correlations inherent in HSI data. The proposed architecture consists of two complementary branches: (1) a Semantic-enhanced Hypergraph Convolutional Network (SSeHGCN) that incorporates category-specific semantic knowledge through a vision-language model to enhance spatial representations, and (2) a Spatial-Spectral enhanced Hypergraph Convolutional Network (SSpHGCN) that captures both intra-superpixel visual features and their interrelationships via a novel Spatial-Spectral Feature and Relation Fusion Module (SSRFM). Extensive experiments on four benchmark datasets demonstrate the superiority of the proposed approach, with DB-HGCN achieving state-of-the-art overall classification accuracy (OA) using only five labeled samples per class. This significant performance gain highlights the effectiveness of our method in addressing the data scarcity challenge in HSI classification.

Pseudouridine is an RNA modification that is widely distributed in both prokaryotes and eukaryotes, and plays a critical role in numerous biological activities. Despite its importance, the precise identification of pseudouridine sites through experimental approaches poses significant challenges, requiring substantial time and resources.Therefore, there is a growing need for computational techniques that can reliably and quickly identify pseudouridine sites from vast amounts of RNA sequencing data. In this study, we propose fuzzy kernel evidence Random Forest (FKeERF) to identify pseudouridine sites. This method is called PseU-FKeERF, which demonstrates high accuracy in identifying pseudouridine sites from RNA sequencing data. The PseU-FKeERF model selected four RNA feature coding schemes with relatively good performance for feature combination, and then input them into the newly proposed FKeERF method for category prediction. FKeERF not only uses fuzzy logic to expand the original feature space, but also combines kernel methods that are easy to interpret in general for category prediction. Both cross-validation tests and independent tests on benchmark datasets have shown that PseU-FKeERF has better predictive performance than several state-of-the-art methods. This new method not only improves the accuracy of pseudouridine site identification, but also provides a certain reference for disease control and related drug development in the future.

Therapeutic peptides are therapeutic agents synthesized from natural amino acids, which can be used as carriers for precisely transporting drugs and can activate the immune system for preventing and treating various diseases. However, screening therapeutic peptides using biochemical assays is expensive, time-consuming, and limited by experimental conditions and biological samples, and there may be ethical considerations in the clinical stage. In contrast, screening therapeutic peptides using machine learning and computational methods is efficient, automated, and can accurately predict potential therapeutic peptides. In this study, a k-nearest neighbor model based on multi-Laplacian and kernel risk sensitive loss was proposed, which introduces a kernel risk loss function derived from the K-local hyperplane distance nearest neighbor model as well as combining the Laplacian regularization method to predict therapeutic peptides. The findings indicated that the suggested approach achieved satisfactory results and could effectively predict therapeutic peptide sequences.

As an epigenetic modification that plays an important role in modifying gene function and controlling gene expression during cell development, DNA N4-methylcytosine (4mC) is still lack of researching. It is therefore necessary to accurately predict the 4mC sites to make fully aware of its mechanism and function. In this paper, we propose a novel model which is called Structural Sparse Regularized Random Vector Functional Link Network (SSR-RVFL) for predicting 4mC sites. Compared with other state-of-the-art methods, SSR-RVFL performs better and achieves higher prediction accuracy. There are total six benchmark datasets used in the experiments, namely C.elegans, D.elanogaster, E.coli, A.thaliana G.subterraneus and G.pickeringii. Our model improves the accuracy by 0.42%, 0.45%, 0.48%, 0.91%, 0.66% and 0.7% on these six benchmark datasets respectively, so it can be regarded as a more effective prediction tool.

Identification of new indications for existing drugs is crucial through the various stages of drug discovery. Computational methods are valuable in establishing meaningful associations between drugs and diseases. However, most methods predict the drug-disease associations based solely on similarity data, neglecting valuable biological and chemical information. These methods often use basic concatenation to integrate information from different modalities, limiting their ability to capture features from a comprehensive and in-depth perspective. Therefore, a novel multimodal framework called AMDGT was proposed to predict new drug associations based on dual-graph transformer modules. By combining similarity data and complex biochemical information, AMDGT understands the multimodal feature fusion of drugs and diseases effectively and comprehensively with an attention-aware modality interaction architecture. Extensive experimental results indicate that AMDGT surpasses state-of-the-art methods in real-world datasets. Moreover, case and molecular docking studies demonstrated that AMDGT is an effective tool for drug repositioning. Our code is available at GitHub: https://github.com/JK-Liu7/AMDGT.

The detection of therapeutic peptides is a topic of immense interest in the biomedical field. Conventional biochemical experiment-based detection techniques are tedious and time-consuming. Computational biology has become a useful tool for improving the detection efficiency of therapeutic peptides. Most computational methods do not consider the deviation caused by noise. To improve the generalization performance of therapeutic peptide prediction methods, this work presents a sequence homology score-based deep fuzzy echo-state network with maximizing mixture correntropy (SHS-DFESN-MMC) model. Our method is compared with the existing methods on eight types of therapeutic peptide datasets. The model parameters are determined by 10 fold cross-validation on their training sets and verified by independent test sets. Across the 8 datasets, the average area under the receiver operating characteristic curve (AUC) values of SHS-DFESN-MMC are the highest on both the training (0.926) and independent sets (0.923).

The accurate prediction of drug-target affinity (DTA) is a crucial step in drug discovery and design. Traditional experiments are very expensive and time-consuming. Recently, deep learning methods have achieved notable performance improvements in DTA prediction. However, one challenge for deep learning-based models is appropriate and accurate representations of drugs and targets, especially the lack of effective exploration of target representations. Another challenge is how to comprehensively capture the interaction information between different instances, which is also important for predicting DTA. In this study, we propose AttentionMGT-DTA, a multi-modal attention-based model for DTA prediction. AttentionMGT-DTA represents drugs and targets by a molecular graph and binding pocket graph, respectively. Two attention mechanisms are adopted to integrate and interact information between different protein modalities and drug-target pairs. The experimental results showed that our proposed model outperformed state-of-the-art baselines on two benchmark datasets. In addition, AttentionMGT-DTA also had high interpretability by modeling the interaction strength between drug atoms and protein residues. Our code is available at https://github.com/JK-Liu7/AttentionMGT-DTA.

De novo drug design is crucial in advancing drug discovery, which aims to generate new drugs with specific pharmacological properties. Recently, deep generative models have achieved inspiring progress in generating drug-like compounds. However, the models prioritize a single target drug generation for pharmacological intervention, neglecting the complicated inherent mechanisms of diseases, and influenced by multiple factors. Consequently, developing novel multi-target drugs that simultaneously target specific targets can enhance anti-tumor efficacy and address issues related to resistance mechanisms. To address this issue and inspired by Generative Pre-trained Transformers (GPT) models, we propose an upgraded GPT model with generative adversarial imitation learning for multi-target molecular generation called MTMol-GPT. The multi-target molecular generator employs a dual discriminator model using the Inverse Reinforcement Learning (IRL) method for a concurrently multi-target molecular generation. Extensive results show that MTMol-GPT generates various valid, novel, and effective multi-target molecules for various complex diseases, demonstrating robustness and generalization capability. In addition, molecular docking and pharmacophore mapping experiments demonstrate the drug-likeness properties and effectiveness of generated molecules potentially improve neuropsychiatric interventions. Furthermore, our model's generalizability is exemplified by a case study focusing on the multi-targeted drug design for breast cancer. As a broadly applicable solution for multiple targets, MTMol-GPT provides new insight into future directions to enhance potential complex disease therapeutics by generating high-quality multi-target molecules in drug discovery.

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool in genomics research, enabling the analysis of gene expression at the individual cell level. However, scRNA-seq data often suffer from a high rate of dropouts, where certain genes fail to be detected in specific cells due to technical limitations. This missing data can introduce biases and hinder downstream analysis. To overcome this challenge, the development of effective imputation methods has become crucial in the field of scRNA-seq data analysis. Here, we propose an imputation method based on robust and non-negative matrix factorization (scRNMF). Instead of other matrix factorization algorithms, scRNMF integrates two loss functions: L2 loss and C-loss. The L2 loss function is highly sensitive to outliers, which can introduce substantial errors. We utilize the C-loss function when dealing with zero values in the raw data. The primary advantage of the C-loss function is that it imposes a smaller punishment for larger errors, which results in more robust factorization when handling outliers. Various datasets of different sizes and zero rates are used to evaluate the performance of scRNMF against other state-of-the-art methods. Our method demonstrates its power and stability as a tool for imputation of scRNA-seq data.

Pseudouridine is a type of abundant RNA modification that is seen in many different animals and is crucial for a variety of biological functions. Accurately identifying pseudouridine sites within the RNA sequence is vital for the subsequent study of various biological mechanisms of pseudouridine. However, the use of traditional experimental methods faces certain challenges. The development of fast and convenient computational methods is necessary to accurately identify pseudouridine sites from RNA sequence information. To address this, we introduce a novel pseudouridine site prediction model called PseU-KeMRF, which can identify pseudouridine sites in three species, H. sapiens, S. cerevisiae, and M. musculus. Through comprehensive analysis, we selected four RNA coding schemes, including binary feature, position-specific trinucleotide propensity based on single strand (PSTNPss), nucleotide chemical property (NCP) and pseudo k-tuple composition (PseKNC). Then the support vector machine-recursive feature elimination (SVM-RFE) method was used for feature selection and the feature subset was optimized. Finally, the best feature subsets are input into the kernel based on multinomial random forests (KeMRF) classifier for cross-validation and independent testing. As a new classification method, compared with the traditional random forest, KeMRF not only improves the node splitting process of decision tree construction based on multinomial distribution, but also combines the easy to interpret kernel method for prediction, which makes the classification performance better. Our results indicate superior predictive performance of PseU-KeMRF over other existing models, which can prove that PseU-KeMRF is a highly competitive predictive model that can successfully identify pseudouridine sites in RNA sequences.

DNA N4-methylcytosine (4mC) site identification is a crucial field in bioinformatics, where machine learning methods have been effectively utilized. Due to the presence of noise, the existing deep learning methods for detecting 4mC have consistently low recognition rates in positive samples. With fuzzy rules and membership functions, fuzzy systems can achieve good results in processing noisy signals. In contrast to traditional fuzzy systems that lack deep feature representation and sample measurement, we introduce novel techniques to enhance generalization and feature representation. By incorporating the neural tangent kernel (NTK) and kernel learning algorithm into the fuzzy system, we propose the fuzzy NTK (FNTK) model and the radius-based FNTK (R-FNTK) model to predict DNA 4mC sites. To achieve better generalization performance than traditional kernel functions, we first train the NTK for feature representation learning and sample measurement. Based on the membership function and NTK matrix, different fuzzy kernel matrices are constructed for each fuzzy subset of the fuzzy system. Finally, we utilize two types of iterative kernel optimization algorithms to effectively fuse multiple NTK-based fuzzy kernels and obtain the final prediction model. Rigorous testing using six benchmark datasets demonstrates the superiority of our approach, yielding significant improvements in the experiment's performance.

Deoxyribonucleic acid(DNA) N6-methyladenine plays a vital role in various biological processes, and the accurate identification of its site can provide a more comprehensive understanding of its biological effects. There are several methods for 6mA site prediction. With the continuous development of technology, traditional techniques with the high costs and low efficiencies are gradually being replaced by computer methods. Computer methods that are widely used can be divided into two categories: traditional machine learning and deep learning methods. We first list some existing experimental methods for predicting the 6mA site, then analyze the general process from sequence input to results in computer methods and review existing model architectures. Finally, the results were summarized and compared to facilitate subsequent researchers in choosing the most suitable method for their work.

Development of robust and effective strategies for synthesizing new compounds, drug targeting and constructing GEnome-scale Metabolic models (GEMs) requires a deep understanding of the underlying biological processes. A critical step in achieving this goal is accurately identifying the categories of pathways in which a compound participated. However, current machine learning-based methods often overlook the multifaceted nature of compounds, resulting in inaccurate pathway predictions. Therefore, we present a novel framework on Multi-View Multi-Label Learning for Metabolic Pathway Inference, hereby named MVML-MPI. First, MVML-MPI learns the distinct compound representations in parallel with corresponding compound encoders to fully extract features. Subsequently, we propose an attention-based mechanism that offers a fusion module to complement these multi-view representations. As a result, MVML-MPI accurately represents and effectively captures the complex relationship between compounds and metabolic pathways and distinguishes itself from current machine learning-based methods. In experiments conducted on the Kyoto Encyclopedia of Genes and Genomes pathways dataset, MVML-MPI outperformed state-of-the-art methods, demonstrating the superiority of MVML-MPI and its potential to utilize the field of metabolic pathway design, which can aid in optimizing drug-like compounds and facilitating the development of GEMs. The code and data underlying this article are freely available at https://github.com/guofei-tju/MVML-MPI. Contact: [email protected], [email protected] or [email protected].

Detection of therapeutic peptide is a major research direction in the current biopharmaceutical field. However, traditional biochemical experimental detection methods take a lot of time. As supplementary methods for biochemical experiments, the computational methods can improve the efficiency of therapeutic peptide detection. Currently, most machine learning-based therapeutic peptide identification algorithms do not consider the processing of noisy samples. We propose a therapeutic peptide classifier, called weighted echo state networks based on subspace projection (WESN-SP), which reduces the bias caused by high-dimensional noisy features and noisy samples. WESN-SP is trained by sparse Bayesian learning algorithm (SBL) and introduces a weight coefficient for each sample by kernel dependence maximization-based subspace projection. The experimental results show that WESN-SP has better performance than other existing methods.

Detecting potential associations between drugs and diseases plays an indispensable role in drug development, which has also become a research hotspot in recent years. Compared with traditional methods, some computational approaches have the advantages of fast speed and low cost, which greatly accelerate the progress of predicting the drug-disease association. In this study, we propose a novel similarity-based method of low-rank matrix decomposition based on multi-graph regularization. On the basis of low-rank matrix factorization with$L_{2}$regularization, the multi-graph regularization constraint is constructed by combining a variety of similarity matrices from drugs and diseases respectively. In the experiments, we analyze the difference in the combination of different similarities, resulting that combining all the similarity information on drug space is unnecessary, and only a part of the similarity information can achieve the desired performance. Then our method is compared with other existing models on three data sets (Fdataset, Cdataset and LRSSLdataset) and have a good advantage in the evaluation measurement of AUPR. Besides, a case study experiment is conducted and showing that the superior ability for predicting the potential disease-related drugs of our model. Finally, we compare our model with some methods on six real world datasets, and our model has a good performance in detecting real world data.

N4-methylcytosine (4mC) is one of important epigenetic modifications in DNA sequences. Detecting 4mC sites is time-consuming. The computational method based on machine learning has provided effective help for identifying 4mC. To further improve the performance of prediction, we propose a Laplacian Regularized Sparse Representation based Classifier with L2,1/2-matrix norm (LapRSRC). We also utilize kernal trick to derive the kernel LapRSRC for nonlinear modeling. Matrix factorization technology is employed to solve the sparse representation coefficients of all test samples in the training set. And an efficient iterative algorithm is proposed to solve the objective function. We implement our model on six benchmark datasets of 4mC and eight UCI datasets to test evaluate performance. The results show that the performance of our method is better or comparable.

DNA-binding proteins (DBPs) have a significant impact on many life activities, so identification of DBPs is a crucial issue. And it is greatly helpful to understand the mechanism of protein-DNA interactions. In traditional experimental methods, it is significant time-consuming and labor-consuming to identify DBPs. In recent years, many researchers have proposed lots of different DBP identification methods based on machine learning algorithm to overcome shortcomings mentioned above. However, most existing methods cannot get satisfactory results. In this paper, we focus on developing a new predictor of DBPs, called Multi-View Hypergraph Restricted Kernel Machines (MV-H-RKM). In this method, we extract five features from the three views of the proteins. To fuse these features, we couple them by means of the shared hidden vector. Besides, we employ the hypergraph regularization to enforce the structure consistency between original features and the hidden vector. Experimental results show that the accuracy of MV-H-RKM is 84.09% and 85.48% on PDB1075 and PDB186 data set respectively, and demonstrate that our proposed method performs better than other state-of-the-art approaches. The code is publicly available at https://github.com/ShixuanGG/MV-H-RKM.

Biologically important effects occur when proteins bind to other substances, of which binding to DNA is a crucial one. Therefore, accurate identification of protein-DNA binding residues is important for further understanding of the protein-DNA interaction mechanism. Although wet-lab methods can accurately obtain the location of bound residues, it requires significant human, financial and time costs. There is thus an urgent need to develop efficient computational-based methods. Most current state-of-the-art methods are two-step approaches: the first step uses a sliding window technique to extract residue features; the second step uses each residue as an input to the model for prediction. This has a negative impact on the efficiency of prediction and ease of use. In this study, we propose a sequence-to-sequence (seq2seq) model that can input the entire protein sequence of variable length and use two modules, Transformer Encoder Block and Feature Extracting Block, for hierarchical feature extraction, where Transformer Encoder Block is used to extract global features, and then Feature Extracting Block is used to extract local features to further improve the recognition capability of the model. The comparison results on two benchmark datasets, namely PDNA-543 and PDNA-41, prove the effectiveness of our method in identifying protein-DNA binding residues.

Membrane proteins are the main undertaker of biomembrane functions and play a vital role in many biological activities of organisms. Prediction of membrane protein types has a great help in determining the function of proteins and understanding the interactions of membrane proteins. However, the biochemical experiment is expensive and not suitable for the large-scale identification of membrane protein types. Therefore, computational methods were used to improve the efficiency of biological experiments. Most existing computational methods only use a single feature of protein, or use multiple features but do not integrate these well. In our study, the protein sequence is described via three different views (features), including amino acid composition, evolutionary information and physicochemical properties of amino acids. To exploit information among all views (features), we introduce a coupling strategy for Kernel Sparse Representation based Classification (KSRC) and construct a new model called Multi-view KSRC (MvKSRC). We implement our method on 4 benchmark data sets of membrane proteins. The comparison results indicate that our method is much superior to all existing methods.

The detection of therapeutic peptides is usually a biochemical experimental method, which is time-consuming and labor-intensive. Lots of computational biology methods had been proposed to solve the problem of therapeutic peptide prediction. However, the existing methods did not consider the processing of noisy samples. We propose a kernel risk-sensitive mean p-power error-based echo state network with sparse learning (KRP-ESN-SL). An efficient iterative optimization algorithm is used to train the model. The KRP-ESN-SL has better performance than other methods.

The outbreak of COVID-19 pandemic has spread rapidly and severely affected all aspects of human lives. Recent researches has shown artificial intelligence and deep learning based approaches have achieved successful results in detecting diseases. How to accurately and quickly detect COVID-19 has always been the core topic of research. In this paper, we propose a novel approach based on prompt learning for COVID-19 diagnosis. Different from the traditional “pre-training, fine-tuning” paradigm, we propose the prompt-based method that redefine the COVID-19 diagnosis as a masked predict task. Specifically, we adopt an attention mechanism to learn the multi-modal representation of medical image and text, and manually construct a cloze prompt template and a label word set. Selecting the label word corresponding to the maximum probability by pre-training language model. Finally, mapping the prediction results to the disease categories. Experimental results show that our proposed method obtains obvious improvement of 1.2% in terms of Mi-F1 score compared with the state-of-the-art methods.

Failure to diagnose and treat depression in a timely manner causes more than three hundred million people suffering from this mental health disorder worldwide. Depression, a global problem, affects not only people’s emotions, but also their physical and mental states. Early detection of depression is very important for the treatment of patients, so we need to achieve excellent accuracy and practicability of depression detection, among which the most important and challenging problem is to design an effective and robust depression detection model. To solve this problem, we propose a hybrid deep learning model, RoBERTa-BiLSTM, to extract features from depression text sequences. We know that the sequence models require a longer computation time as the processing is done sequentially. However, the Transformer models require less execution time with parallelized processing. This model consolidates the strengths of sequence model and Transformer model while suppressing the limitations of sequence model. Specifically, the model maps the words into a compact meaningful word embedding space through the Robustly optimized BERT approach, and then effectively captures the long-distance contextual semantics using the Bidirectional Long Short-Term Memory model. On the DAIC-WOZ and EATD-Corpus benchmark, our experiments demonstrate that our model outperforms state-of-art methods by a substantial margin.

Targeted drugs have been applied to the treatment of cancer on a large scale, and some patients have certain therapeutic effects. It is a time-consuming task to detect drug-target interactions (DTIs) through biochemical experiments. At present, machine learning (ML) has been widely applied in large-scale drug screening. However, there are few methods for multiple information fusion. We propose a multiple kernel-based triple collaborative matrix factorization (MK-TCMF) method to predict DTIs. The multiple kernel matrices (contain chemical, biological and clinical information) are integrated via multi-kernel learning (MKL) algorithm. And the original adjacency matrix of DTIs could be decomposed into three matrices, including the latent feature matrix of the drug space, latent feature matrix of the target space and the bi-projection matrix (used to join the two feature spaces). To obtain better prediction performance, MKL algorithm can regulate the weight of each kernel matrix according to the prediction error. The weights of drug side-effects and target sequence are the highest. Compared with other computational methods, our model has better performance on four test data sets.

In the entire life cycle of drug development, the side effect is one of the major failure factors. Severe side effects of drugs that go undetected until the post-marketing stage leads to around two million patient morbidities every year in the United States. Therefore, there is an urgent need for a method to predict side effects of approved drugs and new drugs. Following this need, we present a new predictor for finding side effects of drugs. Firstly, multiple similarity matrices are constructed based on the association profile feature and drug chemical structure information. Secondly, these similarity matrices are integrated by Centered Kernel Alignment-based Multiple Kernel Learning algorithm. Then, Weighted K nearest known neighbors is utilized to complement the adjacency matrix. Next, we construct Restricted Boltzmann machines (RBM) in drug space and side effect space, respectively, and apply a penalized maximum likelihood approach to train model. At last, the average decision rule was adopted to integrate predictions from RBMs. Comparison results and case studies demonstrate, with four benchmark datasets, that our method can give a more accurate and reliable prediction result.

Current human biomedical research shows that human diseases are closely related to non-coding RNAs, so it is of great significance for human medicine to study the relationship between diseases and non-coding RNAs. Current research has found associations between non-coding RNAs and human diseases through a variety of effective methods, but most of the methods are complex and targeted at a single RNA or disease. Therefore, we urgently need an effective and simple method to discover the associations between non-coding RNAs and human diseases. In this paper, we propose a sparse regularized joint projection model (SRJP) to identify the associations between non-coding RNAs and diseases. First, we extract information through a series of ncRNA similarity matrices and disease similarity matrices and assign average weights to the similarity matrices of the two sides. Then we decompose the similarity matrices of the two spaces into low-rank matrices and put them into SRJP. In SRJP, we innovatively use the projection matrix to combine the ncRNA side and the disease side to identify the associations between ncRNAs and diseases. Finally, the regularization term in SRJP effectively improves the robustness and generalization ability of the model. We test our model on different datasets involving three types of ncRNAs: circRNA, microRNA and long non-coding RNA. The experimental results show that SRJP has superior ability to identify and predict the associations between ncRNAs and diseases.

DNA-binding proteins (DBPs) are of great significance in many basic cellular processes. Experiment-based methods for identifying DBPs are costly and time-consuming. To deal with large-scale DBP identification tasks, a variety of computation-based methods have been developed. Inspired by previous work, we propose a multiple Laplacian regularized support vector machine with local behavior similarity (MLapSVM-LBS) to predict DBP. We serially combine three features that are extracted from protein sequences (including PsePSSM, GE, NMBAC) and feed them into MLapSVM-LBS. Based on human behavior learning theory, MLapSVM-LBS can better represent the relationship between samples through local behavior similarity. We introduce a new edge weight calculation method that takes label information into consideration. In addition, a local distribution parameter reflecting the underlying probability distribution of a sample’s neighborhood is also employed. To further improve the robustness of the model, we utilize multiple Laplacian regularization to build a multigraph model in which five Laplacian graphs are constructed with local behavior similarity by changing the neighborhood size. To appraise the performance of our model, MLapSVM-LBS is trained and tested on the PDB186, PDB1075, PDB2272 and PDB14189 datasets. On two independent testing sets (PDB186 and PDB2272), our method reaches the accuracies of 0.887 and 0.712, respectively. The good results on both datasets demonstrate the reliable performance of our model.

Non-coding RNAs (ncRNAs) play an important role in revealing the mechanism of human disease for anti-tumor and anti-virus substances. Detecting subcellular locations of ncRNAs is a necessary way to study ncRNA. Traditional biochemical methods are time-consuming and labor-intensive, and computational-based methods can help detect the location of ncRNAs on a large scale. However, many models did not consider the correlation information among multiple subcellular localizations of ncRNAs. This study proposes a radial basis function neural network based on shared subspace learning (RBFNN-SSL), which extract shared structures in multi-labels. To evaluate performance, our classifier is tested on three ncRNA datasets. Our model achieves better performance in experimental results.

G protein-coupled receptors (GPCRs) account for about 40% to 50% of drug targets. Many human diseases are related to G protein coupled receptors. Accurate prediction of GPCR interaction is not only essential to understand its structural role, but also helps design more effective drugs. At present, the prediction of GPCR interaction mainly uses machine learning methods. Machine learning methods generally require a large number of independent and identically distributed samples to achieve good results. However, the number of available GPCR samples that have been marked is scarce. Transfer learning has a strong advantage in dealing with such small sample problems. Therefore, this paper proposes a transfer learning method based on sample similarity, using XGBoost as a weak classifier and using the TrAdaBoost algorithm based on JS divergence for data weight initialization to transfer samples to construct a data set. After that, the deep neural network based on the attention mechanism is used for model training. The existing GPCR is used for prediction. In short-distance contact prediction, the accuracy of our method is 0.26 higher than similar methods.

Non-coding RNAs (ncRNAs) are a type of RNAs which are not used to encode protein sequences. Emerging evidence shows that lots of ncRNAs may participate in many biological processes and must be widely involved in many types of cancers. Therefore, understanding their functionality is of great importance. Similar to proteins, various functions of ncRNAs relies on their subcellular localizations. Traditional high-throughput methods in wet-lab to identify subcellular localization is time-consuming and costly. In this paper, we propose a novel computational method based on multi-kernel learning to identify multi-label ncRNA subcellular localizations, via graph regularized k-local hyperplane distance nearest neighbor algorithm. First, we construct six types of sequence-based feature descriptors and select important feature vectors. Then, we build a multi-kernel learning model with Hilbert-Schmidt independence criterion (HSIC) to obtain optimal weights for vairous features. Furthermore, we propose the graph regularized k-local hyperplane distance nearest neighbor algorithm (GHKNN) as a binary classification model for detecting one kind of non-coding RNA subcellular localization. Finally, we apply One-vs-Rest strategy to decompose multi-label problem of non-coding RNA subcellular localizations. Our method achieves excellent performance on three ncRNA datasets and three human ncRNA datasets, and out-performs other outstanding machine learning methods. Comparing to existing method, our model also performs well especially on small datasets. We expect that this model will be useful for the prediction of subcellular localization and the study of important functional mechanisms of ncRNAs. Furthermore, we establish user-friendly web server (http://ncrna.lbci.net/) with the implementation of our method, which can be easily used by most experimental scientists.

DNA methylation is an epigenetic marker that plays an important role in the biological processes of regulating gene expression, maintaining chromatin structure, imprinting genes, inactivating X chromosomes, and developing embryos. The traditional detection method is time-consuming. Currently, researchers have used effective computational methods to improve the efficiency of methylation detection. This study proposes a fuzzy model with correntropy induced loss (C-loss) function to identify DNA N4-methylcytosine (4 mC) sites. To improve the robustness and performance of the model, we use kernel method and the C-loss function to build a higher order fuzzy inference systems. To test performance, our model is implemented on six 4 mC and eight University of California Irvine (UCI) datasets. The experimental results show that our model achieves better prediction performance.

X-ray diffraction and nuclear magnetic resonance spectroscopy are the main methods for measuring membrane proteins. The traditional methods are time-consuming and labor-intensive. To large-scale prediction and screening of membrane proteins, a graph regularized k-local hyperplane distance nearest neighbor model (GHKNN) is proposed to identify of membrane protein types. For effectively integrating features, multi-view learning (MVL) is employed to estimate the weight of each graph. We test GHKNN on 2 data sets of membrane protein. Compared with other methods, the accuracy of GHKNN is better or comparable.

Relationship of accurate associations between non-coding RNAs and diseases could be of great help in the treatment of human biomedical research. However, the traditional technology is only applied on one type of non-coding RNA or a specific disease, and the experimental method is time-consuming and expensive. More computational tools have been proposed to detect new associations based on known ncRNA and disease information. Due to the ncRNAs (circRNAs, miRNAs and lncRNAs) having a close relationship with the progression of various human diseases, it is critical for developing effective computational predictors for ncRNA-disease association prediction. In this paper, we propose a new computational method of three-matrix factorization with hypergraph regularization terms (HGRTMF) based on central kernel alignment (CKA), for identifying general ncRNA-disease associations. In the process of constructing the similarity matrix, various types of similarity matrices are applicable to circRNAs, miRNAs and lncRNAs. Our method achieves excellent performance on five datasets, involving three types of ncRNAs. In the test, we obtain best area under the curve scores of $0.9832$, $0.9775$, $0.9023$, $0.8809$ and $0.9185$ via 5-fold cross-validation and $0.9832$, $0.9836$, $0.9198$, $0.9459$ and $0.9275$ via leave-one-out cross-validation on five datasets. Furthermore, our novel method (CKA-HGRTMF) is also able to discover new associations between ncRNAs and diseases accurately. Availability: Codes and data are available: https://github.com/hzwh6910/ncRNA2Disease.git. Contact:[email protected].

BACKGROUND: RNA secondary structure prediction is an important research content in the field of biological information. Predicting RNA secondary structure with pseudoknots has been proved to be an NP-hard problem. Traditional machine learning methods can not effectively apply protein sequence information with different sequence lengths to the prediction process due to the constraint of the self model when predicting the RNA secondary structure. In addition, there is a large difference between the number of paired bases and the number of unpaired bases in the RNA sequences, which means the problem of positive and negative sample imbalance is easy to make the model fall into a local optimum. To solve the above problems, this paper proposes a variable-length dynamic bidirectional Gated Recurrent Unit(VLDB GRU) model. The model can accept sequences with different lengths through the introduction of flag vector. The model can also make full use of the base information before and after the predicted base and can avoid losing part of the information due to truncation. Introducing a weight vector to predict the RNA training set by dynamically adjusting each base loss function solves the problem of balanced sample imbalance. RESULTS: The algorithm proposed in this paper is compared with the existing algorithms on five representative subsets of the data set RNA STRAND. The experimental results show that the accuracy and Matthews correlation coefficient of the method are improved by 4.7% and 11.4%, respectively. CONCLUSIONS: The flag vector introduced allows the model to effectively use the information before and after the protein sequence; the introduced weight vector solves the problem of unbalanced sample balance. Compared with other algorithms, the LVDB GRU algorithm proposed in this paper has the best detection results.

BACKGROUND: DNA-Binding Proteins (DBP) plays a pivotal role in biological system. A mounting number of researchers are studying the mechanism and detection methods. To detect DBP, the tradition experimental method is time-consuming and resource-consuming. In recent years, Machine Learning methods have been used to detect DBP. However, it is difficult to adequately describe the information of proteins in predicting DNA-binding proteins. In this study, we extract six features from protein sequence and use Multiple Kernel Learning-based on Centered Kernel Alignment to integrate these features. The integrated feature is fed into Support Vector Machine to build predictive model and detect new DBP. RESULTS: In our work, date sets of PDB1075 and PDB186 are employed to test our method. From the results, our model obtains better results (accuracy) than other existing methods on PDB1075 ([Formula: see text]) and PDB186 ([Formula: see text]), respectively. CONCLUSION: Multiple kernel learning could fuse the complementary information between different features. Compared with existing methods, our method achieves comparable and best results on benchmark data sets.

X-ray crystallography is the most popular approach for analyzing protein 3D structure. However, the success rate of protein crystallization is very low (2-10 percent). To reduce the cost of time and resources, lots of computation-based methods are developed to detect the protein crystallization. Improving the accuracy of predicting protein crystallization is very important for the determination of protein structure by X-ray crystallography. At present, many machine learning methods are used to predict protein crystallization. In this article, we propose a Fuzzy Support Vector Machine based on Linear Neighborhood Representation (FSVM-LNR) to predict the crystallization propensity of proteins. Proteins are represented by three types of features (PsePSSM, PSSM-DWT, MMI-PS), and these features are serially combined and fed into FSVM-LNR. FSVM-LNR can filter outliers by membership score, which is calculated via reconstruction residuals of k nearest samples. To evaluate the performance of our predictive model, we test FSVM-LNR on the datasets of TRAIN3587, TEST3585 and TEST500. Our method achieves better Mathew's correlation coefficient (MCC) on TRAIN3587 (MCC: 0.56) and TEST3585 (MCC: 0.58). Although the performance of independent test is not the best on TEST500, FSVM-LNR also has a certain predictability (MCC: 0.70) in the identification of protein crystallization. The good performance on the datasets proves the effectiveness of our method and the better performance on large datasets further demonstrates the stability and superiority of our method.

An enhancer is a short region of DNA with the ability to recruit transcription factors and their complexes, increasing the likelihood of the transcription of a particular gene. Considering the importance of enhancers, enhancer identification is a prevailing problem in computational biology. In this paper, we propose a novel two-layer enhancer predictor called iEnhancer-KL, using computational biology algorithms to identify enhancers and then classify these enhancers into strong or weak types. Kullback-Leibler (KL) divergence is creatively taken into consideration to improve the feature extraction method PSTNPss. Then, LASSO is used to reduce the dimension of features and finally helps to get better prediction performance. Furthermore, the selected features are tested on several machine learning models, and the SVM algorithm achieves the best performance. The rigorous cross-validation indicates that our predictor is remarkably superior to the existing state-of-the-art methods with an Acc of 84.23 percent and the MCC of 0.6849 for identifying enhancers. Our code and results can be freely downloaded from https://github.com/Not-so-middle/iEnhancer-KL.git.

Improving the accuracy of predicting protein crystallization is very important for protein crystallization projects, which is a critical step for the determination of protein structure by X-ray crystallography. At present, many machine learning methods are used to predict protein crystallization. Here, we use a novel feature combination to construct a SVM model in the prediction of protein crystallization, called as CrystalM. In this work, we extract six features to represent protein sequences, namely Average Block-Position specific scoring matrix (AVBlock-PSSM), Average Block-Secondary Structure (AVBlock-SS), Global Encoding (GE), Pseudo-Position specific scoring matrix (PsePSSM), Protscale, and Discrete Wavelet Transform-Position specific scoring matrix (DWT-PSSM). Moreover, we employ two training datasets (TRAIN3587 and TRAIN1500) and their corresponding independent test datasets (TEST3585 and TEST500) to evaluate CrystalM by feeding multi-view features into Support Vector Machine (SVM) classifier. Two training datasets are employed for five-fold cross validation, and two test datasets are separately used to test the corresponding datasets. Finally, we compare CrystalM with other existing methods in the performance. For the datasets of TRAIN3587 and TEST3585, CrystalM achieves best Accuracy (ACC), best Specificity (SP), and the same Mathew's correlation coefficient (MCC) as the previous outperforming methods in the five-fold cross validation. In particular, ACC, SP, and MCC have surpassed the existing methods in independent test, which proves the effectiveness of CrystalM. Meanwhile, ACC, SP, and MCC are higher than existing methods in the five-fold cross validation for TRAIN1500. Although the performance of independent test for TEST500 is not the best, CrystalM also has a certain predictability in the prediction of protein crystallization. In addition, we find that only choosing the first four features can improve the performance of prediction for TRAIN1500 and TEST500, not only in independent tests but also in five-fold cross validation. This phenomenon indicates that the latter two features can not effectively represent proteins of TRAIN1500 and TEST500. CrystalM is a sequence-based protein crystallization prediction method. The good performance on the datasets proves the effectiveness of CrystalM and the better performance on large datasets further demonstrates the stability and superiority of CrystalM.

Approximately 40-50 percent of all drugs targets are G protein-coupled receptors (GPCRs). Three-dimensional structure of GPCRs is important to probe their biophysical and biochemical functions and their pharmaceutical applications. Lacking reliable and high quality free function is one of the ugent problems of computational predicting the three-dimensional structure in this community. We proposed a GPCR-specified energy function composed of four novel empirical potential energy terms: a two-dimensional contact energy force field, knowledge-based helix pair connection distance energy term, knowledge-based helix pair angle restraint energy term and a disulfide bond energy term. To validate the energy function, we employed an ab initio GPCR three-dimensional structure predictor to test if the energy function improved the accuracy of prediction. We evaluated 28 solved GPCRs and found that 21(75 percent) targets were correctly folded (TM-score>0.5). Also, the average TM-score using the energy function was 0.54, which was improved 134 percent than the TM-score 0.23 for MODELLER energy function and 170 percent than the TM-score 0.20 for Rosetta membrane energy function. The results confirmed that our empirical potential energy function toward ab initio folding is competitive to state-of-the-art solutions for structural prediction of GPCRs.

DNase I hypersensitive sites (DHSs) have proven to be tightly associated with cis-regulatory elements, commonly indicating specific function on the chromatin structure. Thus, identifying DHSs plays a fundamental role in decoding gene regulatory behavior. While traditional experimental methods turn to be time-consuming and expensive, computational techniques promise to be practical to discovering and analyzing regulatory factors. In this study, we applied an efficient model that considered composition information and physicochemical properties and effectively selected features with a boosting algorithm. CEPZ, our predictor, greatly improved a Matthews correlation coefficient and accuracy of 0.7740 and 0.9113 respectively, more competitive than any predictor before. This result suggests that it may become a useful tool for DHSs research in the human and other complex genomes. Our research was anchored on the properties of dinucleotides and we identified several dinucleotides with significant differences in the distribution of DHS and non-DHS samples, which are likely to have a special meaning in the chromatin structure. The datasets, feature sets and the relevant algorithm are available at https://github.com/YanZheng-16/CEPZ_DHS/.

Antimicrobial peptides (AMPs) are innate immune molecules that exhibit activities against a range of microbes. According to their special functions, AMPs are generally classified into several categories. Over the last decade, a number of AMP prediction tools have been designed and made freely available online, which show potential to discriminate AMPs from non-AMPs. However, the relative quality of existing AMP predictions produced by various tools is difficult to quantify. In fact, a comprehensive benchmark dataset used to train the prediction model is one of key points to solving the problem. Also, how to address the multi-label character of new synthetic instance is obviously very important to both basic research and drug development. In view of this, AMPs prediction should be a task of two-level multi-label classification, in which the first step is to identify whether a query peptide is AMP, and the second step is to identify which functional type(s) the peptide belongs to. To establish a really useful prediction method, we construct a valid benchmark dataset to train the predictor, and develop a powerful algorithm to operate the prediction. In this paper, we propose a novel two-layer prediction model for identifying AMP and its functional types, using ADASYN oversampling technology to solve imbalance multi-label classification problem. First, we construct a novel benchmark AMPs dataset with seven different AMP functional types. Then, we encode AMPs within three different feature representations, and use various feature extraction models to convert the variable length coding matrix into some equidimensional features. Furthermore, we use modelbased feature selection method for filtering effective and sparse features. Finally, we apply ensemble classifier chain model to identify whether a query peptide is an AMPs or non-AMPs. In the second layer prediction, we use ADASYN to oversample different functional types of AMPs, and build a multi-label multi-class prediction model to identify which functional type(s) it belongs to. To be specific, our novel method outperforms outstanding rather than other tools in most respects on our novel benchmark datasets. Our novel benchmark dataset and source codes are available at https://github.com/guofei-tju/Two_Level_Ensemble-classifier-chain.

Human protein subcellular localization has an important research value in biological processes, also in elucidating protein functions and identifying drug targets. Over the past decade, a number of protein subcellular localization prediction tools have been designed and made freely available online. The purpose of this paper is to summarize the progress of research on the subcellular localization of human proteins in recent years, including commonly used data sets proposed by the predecessors and the performance of all selected prediction tools against the same benchmark data set. We carry out a systematic evaluation of several publicly available subcellular localization prediction methods on various benchmark data sets. Among them, we find that mLASSO-Hum and pLoc-mHum provide a statistically significant improvement in performance, as measured by the value of accuracy, relative to the other methods. Meanwhile, we build a new data set using the latest version of Uniprot database and construct a new GO-based prediction method HumLoc-LBCI in this paper. Then, we test all selected prediction tools on the new data set. Finally, we discuss the possible development directions of human protein subcellular localization. Availability: The codes and data are available from http://www.lbci.cn/syn/.

BACKGROUND: In ab initio protein-structure predictions, a large set of structural decoys are often generated, with the requirement to select best five or three candidates from the decoys. The clustered central structures with the most number of neighbors are frequently regarded as the near-native protein structures with the lowest free energy; however, limitations in clustering methods and three-dimensional structural-distance assessments make identifying exact order of the best five or three near-native candidate structures difficult. RESULTS: To address this issue, we propose a method that re-ranks the candidate structures via random forest classification using intra- and inter-cluster features from the results of the clustering. Comparative analysis indicated that our method was better able to identify the order of the candidate structures as comparing with current methods SPICKR, Calibur, and Durandal. The results confirmed that the identification of the first model were closer to the native structure in 12 of 43 cases versus four for SPICKER, and the same as the native structure in up to 27 of 43 cases versus 14 for Calibur and up to eight of 43 cases versus two for Durandal. CONCLUSIONS: In this study, we presented an improved method based on random forest classification to transform the problem of re-ranking the candidate structures by an binary classification. Our results indicate that this method is a powerful method for the problem and the effect of this method is better than other methods.

Drug-side effect association contains the information on marketed medicines and their recorded adverse drug reactions. Traditional experimental method is time consuming and expensive. All associations of drugs and side-effects are seen as a bipartite network. Therefore, many computational approaches have been developed to deal with this problem, which are used to predict new potential associations. However, lots of methods did not consider multiple kernel learning (MKL) algorithm, which can integrate multiple sources of information and further improve prediction performance. In this study, we develop a novel predictor of drug-side effect association. First, we build multiple kernels from drug space and side-effect space. What is more, these corresponding kernels are linear weighted by MKL algorithm in drug space and side-effect space, respectively. Finally, a graph-based semisupervised learning is employed to construct drug-side effect predictor. Compared with existing methods, our method achieves better results on three benchmark data sets. The values of area under the precision recall curve are 0.668, 0.673, and 0.670 on three benchmark data sets, respectively. Our method is a useful tool for the side-effects prediction of drugs.

BACKGROUND: Protein-protein interactions (PPIs) are central to a lot of biological processes. Many algorithms and methods have been developed to predict PPIs and protein interaction networks. However, the application of most existing methods is limited since they are difficult to compute and rely on a large number of homologous proteins and interaction marks of protein partners. In this paper, we propose a novel sequence-based approach with multivariate mutual information (MMI) of protein feature representation, for predicting PPIs via Random Forest (RF). METHODS: Our method constructs a 638-dimentional vector to represent each pair of proteins. First, we cluster twenty standard amino acids into seven function groups and transform protein sequences into encoding sequences. Then, we use a novel multivariate mutual information feature representation scheme, combined with normalized Moreau-Broto Autocorrelation, to extract features from protein sequence information. Finally, we feed the feature vectors into a Random Forest model to distinguish interaction pairs from non-interaction pairs. RESULTS: To evaluate the performance of our new method, we conduct several comprehensive tests for predicting PPIs. Experiments show that our method achieves better results than other outstanding methods for sequence-based PPIs prediction. Our method is applied to the S.cerevisiae PPIs dataset, and achieves 95.01 % accuracy and 92.67 % sensitivity repectively. For the H.pylori PPIs dataset, our method achieves 87.59 % accuracy and 86.81 % sensitivity respectively. In addition, we test our method on other three important PPIs networks: the one-core network, the multiple-core network, and the crossover network. CONCLUSIONS: Compared to the Conjoint Triad method, accuracies of our method are increased by 6.25,2.06 and 18.75 %, respectively. Our proposed method is a useful tool for future proteomics studies.