Integrated convolution and self-attention for improving peptide toxicity prediction.

MOTIVATION: Peptides are promising agents for the treatment of a variety of diseases due to their specificity and efficacy. However, the development of peptide-based drugs is often hindered by the potential toxicity of peptides, which poses a significant barrier to their clinical application. Traditional experimental methods for evaluating peptide toxicity are time-consuming and costly, making the development process inefficient. Therefore, there is an urgent need for computational tools specifically designed to predict peptide toxicity accurately and rapidly, facilitating the identification of safe peptide candidates for drug development. RESULTS: We provide here a novel computational approach, CAPTP, which leverages the power of convolutional and self-attention to enhance the prediction of peptide toxicity from amino acid sequences. CAPTP demonstrates outstanding performance, achieving a Matthews correlation coefficient of approximately 0.82 in both cross-validation settings and on independent test datasets. This performance surpasses that of existing state-of-the-art peptide toxicity predictors. Importantly, CAPTP maintains its robustness and generalizability even when dealing with data imbalances. Further analysis by CAPTP reveals that certain sequential patterns, particularly in the head and central regions of peptides, are crucial in determining their toxicity. This insight can significantly inform and guide the design of safer peptide drugs. AVAILABILITY AND IMPLEMENTATION: The source code for CAPTP is freely available at https://github.com/jiaoshihu/CAPTP.

CodLncScape Provides a Self-Enriching Framework for the Systematic Collection and Exploration of Coding LncRNAs.

Recent studies have revealed that numerous lncRNAs can translate proteins under specific conditions, performing diverse biological functions, thus termed coding lncRNAs. Their comprehensive landscape, however, remains elusive due to this field's preliminary and dispersed nature. This study introduces codLncScape, a framework for coding lncRNA exploration consisting of codLncDB, codLncFlow, codLncWeb, and codLncNLP. Specifically, it contains a manually compiled knowledge base, codLncDB, encompassing 353 coding lncRNA entries validated by experiments. Building upon codLncDB, codLncFlow investigates the expression characteristics of these lncRNAs and their diagnostic potential in the pan-cancer context, alongside their association with spermatogenesis. Furthermore, codLncWeb emerges as a platform for storing, browsing, and accessing knowledge concerning coding lncRNAs within various programming environments. Finally, codLncNLP serves as a knowledge-mining tool to enhance the timely content inclusion and updates within codLncDB. In summary, this study offers a well-functioning, content-rich ecosystem for coding lncRNA research, aiming to accelerate systematic studies in this field.

Multi-party collaborative drug discovery via federated learning.

In the field of drug discovery and pharmacology research, precise and rapid prediction of drug-target binding affinity (DTA) and drug-drug interaction (DDI) are essential for drug efficacy and safety. However, pharmacological data are often distributed across different institutions. Moreover, due to concerns regarding data privacy and intellectual property, the sharing of pharmacological data is often restricted. It is difficult for institutions to achieve the desired performance by solely utilizing their data. This urgent challenge calls for a solution that not only enhances collaboration between multiple institutions to improve prediction accuracy but also safeguards data privacy. In this study, we propose a novel federated learning (FL) framework to advance the prediction of DTA and DDI, namely FL-DTA and FL-DDI. The proposed framework enables multiple institutions to collaboratively train a predictive model without the need to share their local data. Moreover, to ensure data privacy, we employ secure multi-party computation (MPC) during the federated learning model aggregation phase. We evaluated the proposed method on two DTA and one DDI benchmark datasets and compared them with centralized learning and local learning. The experimental results indicate that the proposed method performs closely to centralized learning, and significantly outperforms local learning. Moreover, the proposed framework ensures data security while promoting collaboration among institutions, thereby accelerating the drug discovery process.

A BERT-based model for the prediction of lncRNA subcellular localization in Homo sapiens.

Understanding the subcellular localization of lncRNAs is crucial for comprehending their regulation activities. The conventional detection of lncRNA subcellular location usually uses in situ detection techniques, which are resource intensive. Some machine learning-based algorithms have been proposed for lncRNA subcellular location prediction in mammals. However, due to the low level of conservation of lncRNA sequence, the performance of cross-species models remains unsatisfactory. In this study, we curated a novel dataset containing subcellular location information of lncRNAs in Homo sapiens. Subsequently, based on the BERT pre-trained language algorithm, we developed a model for lncRNA subcellular location prediction. Our model achieved a micro-average area under the receiver operating characteristic (AUROC) of 0.791 on the training set and an AUROC of 0.700 on the testing nucleus set. Additionally, we conducted cross-species validation and motif discovery to further investigate underlying patterns. In summary, our study provides valuable guidance and computational analysis tools for exploring the mechanisms of lncRNA subcellular localization and the dynamic spatial changes of RNA in abnormal physiological states.

FIAMol-AB: A feature fusion and attention-based deep learning method for enhanced antibiotic discovery.

Antibiotic resistance continues to be a growing concern for global health, accentuating the need for novel antibiotic discoveries. Traditional methodologies in this field have relied heavily on extensive experimental screening, which is often time-consuming and costly. Contrastly, computer-assisted drug screening offers rapid, cost-effective solutions. In this work, we propose FIAMol-AB, a deep learning model that combines graph neural networks, text convolutional networks and molecular fingerprint techniques. This method also combines an attention mechanism to fuse multiple forms of information within the model. The experiments show that FIAMol-AB may offer potential advantages in antibiotic discovery tasks over some existing methods. We conducted some analysis based on our model's results, which help highlight the potential significance of certain features in the model's predictive performance. Compared to different models, ours demonstrate promising results, indicating potential robustness and versatility. This suggests that by integrating multi-view information and attention mechanisms, FIAMol-AB might better learn complex molecular structures, potentially improving the precision and efficiency of antibiotic discovery. We hope our FIAMol-AB can be used as a useful method in the ongoing fight against antibiotic resistance.

Pick-up point recommendation strategy based on user incentive mechanism.

In recent years, with the development of spatial crowdsourcing technology, online car-hailing, as a typical spatiotemporal crowdsourcing task application scenario, has attracted widespread attention. Existing researches on spatial crowdsourcing are mainly based on the coordinate positions of user and worker roles to achieve task allocation with the goal of maximum matching number or lowest cost. However, they ignores the problem of the selection of the pick-up point which needs to be solved in the actual scene of online car booking. This problem needs to take into account the four-dimensional coordinate positions of users, workers, pick-up point and destination. Based on this, this study designs a pick-up point recommendation strategy based on user incentive mechanism. Firstly, a new four-dimensional crowdsourcing model is established, which is closer to the practical application of crowdsourcing problem. Secondly, taking cost optimization as the index, a user incentive mechanism is designed to encourage users to walk to the appropriate pick-up point within a certain distance. Thirdly, a concept of forward rate is proposed to reduce the computation time. Some key factors, such as the maximum walking distance limit of users and task cost, are considered as the recommendation index for measuring the pick-up point. Then, an effective pick-up point recommendation strategy is designed based on this index. Experiments show that the strategy proposed in this article can achieve reasonable recommendation for pick-up points and improve the efficiency of drivers and reduce the total trip cost of orders to the greatest extent.

Unravelling cancer subtype-specific driver genes in single-cell transcriptomics data with CSDGI.

Cancer is known as a heterogeneous disease. Cancer driver genes (CDGs) need to be inferred for understanding tumor heterogeneity in cancer. However, the existing computational methods have identified many common CDGs. A key challenge exploring cancer progression is to infer cancer subtype-specific driver genes (CSDGs), which provides guidane for the diagnosis, treatment and prognosis of cancer. The significant advancements in single-cell RNA-sequencing (scRNA-seq) technologies have opened up new possibilities for studying human cancers at the individual cell level. In this study, we develop a novel unsupervised method, CSDGI (Cancer Subtype-specific Driver Gene Inference), which applies Encoder-Decoder-Framework consisting of low-rank residual neural networks to inferring driver genes corresponding to potential cancer subtypes at the single-cell level. To infer CSDGs, we apply CSDGI to the tumor single-cell transcriptomics data. To filter the redundant genes before driver gene inference, we perform the differential expression genes (DEGs). The experimental results demonstrate CSDGI is effective to infer driver genes that are cancer subtype-specific. Functional and disease enrichment analysis shows these inferred CSDGs indicate the key biological processes and disease pathways. CSDGI is the first method to explore cancer driver genes at the cancer subtype level. We believe that it can be a useful method to understand the mechanisms of cell transformation driving tumours.

Adaptive learning embedding features to improve the predictive performance of SARS-CoV-2 phosphorylation sites.

MOTIVATION: The rapid and extensive transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented global health emergency, affecting millions of people and causing an immense socioeconomic impact. The identification of SARS-CoV-2 phosphorylation sites plays an important role in unraveling the complex molecular mechanisms behind infection and the resulting alterations in host cell pathways. However, currently available prediction tools for identifying these sites lack accuracy and efficiency. RESULTS: In this study, we presented a comprehensive biological function analysis of SARS-CoV-2 infection in a clonal human lung epithelial A549 cell, revealing dramatic changes in protein phosphorylation pathways in host cells. Moreover, a novel deep learning predictor called PSPred-ALE is specifically designed to identify phosphorylation sites in human host cells that are infected with SARS-CoV-2. The key idea of PSPred-ALE lies in the use of a self-adaptive learning embedding algorithm, which enables the automatic extraction of context sequential features from protein sequences. In addition, the tool uses multihead attention module that enables the capturing of global information, further improving the accuracy of predictions. Comparative analysis of features demonstrated that the self-adaptive learning embedding features are superior to hand-crafted statistical features in capturing discriminative sequence information. Benchmarking comparison shows that PSPred-ALE outperforms the state-of-the-art prediction tools and achieves robust performance. Therefore, the proposed model can effectively identify phosphorylation sites assistant the biomedical scientists in understanding the mechanism of phosphorylation in SARS-CoV-2 infection. AVAILABILITY AND IMPLEMENTATION: PSPred-ALE is available at https://github.com/jiaoshihu/PSPred-ALE and Zenodo (https://doi.org/10.5281/zenodo.8330277).

Collaborative analysis for drug discovery by federated learning on non-IID data.

With the increasing availability of large-scale QSAR (Quantitative Structure-Activity Relationship) datasets, collaborative analysis has become a promising approach for drug discovery. Traditional centralized analysis which typically concentrates data on a central server for training faces challenges such as data privacy and security. Distributed analysis such as federated learning offers a solution by enabling collaborative model training without sharing raw data. However, it may fail when the training data in the local devices are non-independent and identically distributed (non-IID). In this paper, we propose a novel framework for collaborative drug discovery using federated learning on non-IID datasets. We address the difficulty of training on non-IID data by globally sharing a small subset of data among all institutions. Our framework allows multiple institutions to jointly train a robust predictive model while preserving the privacy of their individual data. We leverage the federated learning paradigm to distribute the model training process across local devices, eliminating the need for data exchange. The experimental results on 15 benchmark datasets demonstrate that the proposed method achieves competitive predictive accuracy to centralized analysis while respecting data privacy. Moreover, our framework offers benefits such as reduced data transmission and enhanced scalability, making it suitable for large-scale collaborative drug discovery efforts.

Multi-omics clustering for cancer subtyping based on latent subspace learning.

The increased availability of high-throughput technologies has enabled biomedical researchers to learn about disease etiology across multiple omics layers, which shows promise for improving cancer subtype identification. Many computational methods have been developed to perform clustering on multi-omics data, however, only a few of them are applicable for partial multi-omics in which some samples lack data in some types of omics. In this study, we propose a novel multi-omics clustering method based on latent sub-space learning (MCLS), which can deal with the missing multi-omics for clustering. We utilize the data with complete omics to construct a latent subspace using PCA-based feature extraction and singular value decomposition (SVD). The data with incomplete multi-omics are then projected to the latent subspace, and spectral clustering is performed to find the clusters. The proposed MCLS method is evaluated on seven different cancer datasets on three levels of omics in both full and partial cases compared to several state-of-the-art methods. The experimental results show that the proposed MCLS method is more efficient and effective than the compared methods for cancer subtype identification in multi-omics data analysis, which provides important references to a comprehensive understanding of cancer and biological mechanisms. AVAILABILITY: The proposed method can be freely accessible at https://github.com/ShangCS/MCLS.

Bidirectional k-nearest neighbor spatial crowdsourcing allocation protocol based on edge computing.

Spatial crowdsourcing refers to the allocation of crowdsourcing workers to each task based on location information. K-nearest neighbor technology has been widely applied in crowdsourcing applications for crowdsourcing allocation. However, there are still several issues need to be stressed. Most of the existing spatial crowdsourcing allocation schemes operate on a centralized framework, resulting in low efficiency of crowdsourcing allocation. In addition, these spatial crowdsourcing allocation schemes are one-way allocation, that is, the suitable matching objects for each task can be queried from the set of crowdsourcing workers, but cannot query in reverse. In this article, a bidirectional k-nearest neighbor spatial crowdsourcing allocation protocol based on edge computing (BKNN-CAP) is proposed. Firstly, a spatial crowdsourcing task allocation framework based on edge computing (SCTAFEC) is established, which can offload all tasks to edge nodes in edge computing layer to realize parallel processing of spatio-temporal queries. Secondly, the positive k-nearest neighbor spatio-temporal query algorithm (PKNN) and reverse k-nearest neighbor spatio-temporal query algorithm (RKNN) are proposed to make the task publishers and crowdsourcing workers conduct two-way query. In addition, a road network distance calculation method is proposed to improve the accuracy of Euclidean distance in spatial query scenarios. Experimental results show that the proposed protocol has less time cost and higher matching success rate compared with other ones.

MRMD3.0: A Python Tool and Webserver for Dimensionality Reduction and Data Visualization via an Ensemble Strategy.

Dimensionality reduction is a hot topic in machine learning that can help researchers find key features from complex medical or biological data, which is crucial for biological sequence research, drug development, etc. However, when applied to specific datasets, different dimensionality reduction methods generate different results, which produces instability and makes tuning the parameters a time-consuming task. Exploring high quality features, genes, or attributes from complex data is an important task and challenge. To ensure the efficiency, robustness, and accuracy of experiments, in this work, we developed a dimensionality reduction tool MRMD3.0 based on the ensemble strategy of link analysis. It is mainly divided into two steps: first, the ensemble method is used to integrate different feature ranking algorithms to calculate feature importance, and then the forward feature search strategy combined with cross-validation is used to explore the proper feature combination. Compared with the previously developed version, MRMD3.0 has added more link-based ensemble algorithms, including PageRank, HITS, LeaderRank, and TrustRank. At the same time, more feature ranking algorithms have been added, and their effect and calculation speed have been greatly improved. In addition, the newest version provides an interface used by each feature ranking method and five kinds of charts to help users analyze features. Finally, we also provide an online webserver to help researchers analyze the data. Availability and implementation Webserver: http://lab.malab.cn/soft/MRMDv3/home.html. GitHub: https://github.com/heshida01/MRMD3.0.

m5U-SVM: identification of RNA 5-methyluridine modification sites based on multi-view features of physicochemical features and distributed representation.

BACKGROUND: RNA 5-methyluridine (m5U) modifications are obtained by methylation at the C5 position of uridine catalyzed by pyrimidine methylation transferase, which is related to the development of human diseases. Accurate identification of m5U modification sites from RNA sequences can contribute to the understanding of their biological functions and the pathogenesis of related diseases. Compared to traditional experimental methods, computational methods developed based on machine learning with ease of use can identify modification sites from RNA sequences in an efficient and time-saving manner. Despite the good performance of these computational methods, there are some drawbacks and limitations. RESULTS: In this study, we have developed a novel predictor, m5U-SVM, based on multi-view features and machine learning algorithms to construct predictive models for identifying m5U modification sites from RNA sequences. In this method, we used four traditional physicochemical features and distributed representation features. The optimized multi-view features were obtained from the four fused traditional physicochemical features by using the two-step LightGBM and IFS methods, and then the distributed representation features were fused with the optimized physicochemical features to obtain the new multi-view features. The best performing classifier, support vector machine, was identified by screening different machine learning algorithms. Compared with the results, the performance of the proposed model is better than that of the existing state-of-the-art tool. CONCLUSIONS: m5U-SVM provides an effective tool that successfully captures sequence-related attributes of modifications and can accurately predict m5U modification sites from RNA sequences. The identification of m5U modification sites helps to understand and delve into the related biological processes and functions.

Molecular language models: RNNs or transformer?

Language models have shown the capacity to learn complex molecular distributions. In the field of molecular generation, they are designed to explore the distribution of molecules, and previous studies have demonstrated their ability to learn molecule sequences. In the early times, recurrent neural networks (RNNs) were widely used for feature extraction from sequence data and have been used for various molecule generation tasks. In recent years, the attention mechanism for sequence data has become popular. It captures the underlying relationships between words and is widely applied to language models. The Transformer-Layer, a model based on a self-attentive mechanism, also shines the same as the RNN-based model. In this research, we investigated the difference between RNNs and the Transformer-Layer to learn a more complex distribution of molecules. For this purpose, we experimented with three different generative tasks: the distributions of molecules with elevated scores of penalized LogP, multimodal distributions of molecules and the largest molecules in PubChem. We evaluated the models on molecular properties, basic metrics, Tanimoto similarity, etc. In addition, we applied two different representations of the molecule, SMILES and SELFIES. The results show that the two language models can learn complex molecular distributions and SMILES-based representation has better performance than SELFIES. The choice between RNNs and the Transformer-Layer needs to be based on the characteristics of dataset. RNNs work better on data focus on local features and decreases with multidistribution data, while the Transformer-Layer is more suitable when meeting molecular with larger weights and focusing on global features.

Deep generative model for drug design from protein target sequence.

Drug discovery for a protein target is a laborious and costly process. Deep learning (DL) methods have been applied to drug discovery and successfully generated novel molecular structures, and they can substantially reduce development time and costs. However, most of them rely on prior knowledge, either by drawing on the structure and properties of known molecules to generate similar candidate molecules or extracting information on the binding sites of protein pockets to obtain molecules that can bind to them. In this paper, DeepTarget, an end-to-end DL model, was proposed to generate novel molecules solely relying on the amino acid sequence of the target protein to reduce the heavy reliance on prior knowledge. DeepTarget includes three modules: Amino Acid Sequence Embedding (AASE), Structural Feature Inference (SFI), and Molecule Generation (MG). AASE generates embeddings from the amino acid sequence of the target protein. SFI inferences the potential structural features of the synthesized molecule, and MG seeks to construct the eventual molecule. The validity of the generated molecules was demonstrated by a benchmark platform of molecular generation models. The interaction between the generated molecules and the target proteins was also verified on the basis of two metrics, drug-target affinity and molecular docking. The results of the experiments indicated the efficacy of the model for direct molecule generation solely conditioned on amino acid sequence.

Interactive gene identification for cancer subtyping based on multi-omics clustering.

Recent advances in multi-omics databases offer the opportunity to explore complex systems of cancers across hierarchical biological levels. Some methods have been proposed to identify the genes that play a vital role in disease development by integrating multi-omics. However, the existing methods identify the related genes separately, neglecting the gene interactions that are related to the multigenic disease. In this study, we develop a learning framework to identify the interactive genes based on multi-omics data including gene expression. Firstly, we integrate different omics based on their similarities and apply spectral clustering for cancer subtype identification. Then, a gene co-expression network is construct for each cancer subtype. Finally, we detect the interactive genes in the co-expression network by learning the dense subgraphs based on the L1 prosperities of eigenvectors in the modularity matrix. We apply the proposed learning framework on a multi-omics cancer dataset to identify the interactive genes for each cancer subtype. The detected genes are examined by DAVID and KEGG tools for systematic gene ontology enrichment analysis. The analysis results show that the detected genes have relationships to cancer development and the genes in different cancer subtypes are related to different biological processes and pathways, which are expected to yield important references for understanding tumor heterogeneity and improving patient survival.

SiameseCPP: a sequence-based Siamese network to predict cell-penetrating peptides by contrastive learning.

BACKGROUND: Cell-penetrating peptides (CPPs) have received considerable attention as a means of transporting pharmacologically active molecules into living cells without damaging the cell membrane, and thus hold great promise as future therapeutics. Recently, several machine learning-based algorithms have been proposed for predicting CPPs. However, most existing predictive methods do not consider the agreement (disagreement) between similar (dissimilar) CPPs and depend heavily on expert knowledge-based handcrafted features. RESULTS: In this study, we present SiameseCPP, a novel deep learning framework for automated CPPs prediction. SiameseCPP learns discriminative representations of CPPs based on a well-pretrained model and a Siamese neural network consisting of a transformer and gated recurrent units. Contrastive learning is used for the first time to build a CPP predictive model. Comprehensive experiments demonstrate that our proposed SiameseCPP is superior to existing baseline models for predicting CPPs. Moreover, SiameseCPP also achieves good performance on other functional peptide datasets, exhibiting satisfactory generalization ability.

Enhanced Authenticated Key Agreement for Surgical Applications in a Tactile Internet Environment.

The Tactile Internet enables physical touch to be transmitted over the Internet. In the context of electronic medicine, an authenticated key agreement for the Tactile Internet allows surgeons to perform operations via robotic systems and receive tactile feedback from remote patients. The fifth generation of networks has completely changed the network space and has increased the efficiency of the Tactile Internet with its ultra-low latency, high data rates, and reliable connectivity. However, inappropriate and insecure authentication key agreements for the Tactile Internet may cause misjudgment and improper operation by medical staff, endangering the life of patients. In 2021, Kamil et al. developed a novel and lightweight authenticated key agreement scheme that is suitable for remote surgery applications in the Tactile Internet environment. However, their scheme directly encrypts communication messages with constant secret keys and directly stores secret keys in the verifier table, making the scheme vulnerable to possible attacks. Therefore, in this investigation, we discuss the limitations of the scheme proposed by Kamil scheme and present an enhanced scheme. The enhanced scheme is developed using a one-time key to protect communication messages, whereas the verifier table is protected with a secret gateway key to mitigate the mentioned limitations. The enhanced scheme is proven secure against possible attacks, providing more security functionalities than similar schemes and retaining a lightweight computational cost.

iLoc-miRNA: extracellular/intracellular miRNA prediction using deep BiLSTM with attention mechanism.

The location of microRNAs (miRNAs) in cells determines their function in regulation activity. Studies have shown that miRNAs are stable in the extracellular environment that mediates cell-to-cell communication and are located in the intracellular region that responds to cellular stress and environmental stimuli. Though in situ detection techniques of miRNAs have made great contributions to the study of the localization and distribution of miRNAs, miRNA subcellular localization and their role are still in progress. Recently, some machine learning-based algorithms have been designed for miRNA subcellular location prediction, but their performance is still far from satisfactory. Here, we present a new data partitioning strategy that categorizes functionally similar locations for the precise and instructive prediction of miRNA subcellular location in Homo sapiens. To characterize the localization signals, we adopted one-hot encoding with post padding to represent the whole miRNA sequences, and proposed a deep bidirectional long short-term memory with the multi-head self-attention algorithm to model. The algorithm showed high selectivity in distinguishing extracellular miRNAs from intracellular miRNAs. Moreover, a series of motif analyses were performed to explore the mechanism of miRNA subcellular localization. To improve the convenience of the model, a user-friendly web server named iLoc-miRNA was established (http://iLoc-miRNA.lin-group.cn/).