IEEE/ACM Transactions on Computational Biology and Bioinformatics最新文献

{"title":"Hierarchical Hypergraph Learning in Association- Weighted Heterogeneous Network for miRNA- Disease Association Identification","authors":"Qiao Ning;Yaomiao Zhao;Jun Gao;Chen Chen;Minghao Yin","doi":"10.1109/TCBB.2024.3485788","DOIUrl":"10.1109/TCBB.2024.3485788","url":null,"abstract":"MicroRNAs (miRNAs) play a significant role in cell differentiation, biological development as well as the occurrence and growth of diseases. Although many computational methods contribute to predicting the association between miRNAs and diseases, they do not fully explore the attribute information contained in associated edges between miRNAs and diseases. In this study, we propose a new method, Hierarchical Hypergraph learning in Association-Weighted heterogeneous network for MiRNA-Disease association identification (HHAWMD). HHAWMD first adaptively fuses multi-view similarities based on channel attention and distinguishes the relevance of different associated relationships according to changes in expression levels of disease-related miRNAs, miRNA similarity information, and disease similarity information. Then, HHAWMD assigns edge weights and attribute features according to the association level to construct an association-weighted heterogeneous graph. Next, HHAWMD extracts the subgraph of the miRNA-disease node pair from the heterogeneous graph and builds the hyperedge (a kind of virtual edge) between the node pair to generate the hypergraph. Finally, HHAWMD proposes a hierarchical hypergraph learning approach, including node-aware attention and hyperedge-aware attention, which aggregates the abundant semantic information contained in deep and shallow neighborhoods to the hyperedge in the hypergraph. Our experiment results suggest that HHAWMD has better performance and can be used as a powerful tool for miRNA-disease association identification.","PeriodicalId":13344,"journal":{"name":"IEEE/ACM Transactions on Computational Biology and Bioinformatics","volume":"21 6","pages":"2531-2542"},"PeriodicalIF":3.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"circ2DGNN: circRNA-Disease Association Prediction via Transformer-Based Graph Neural Network","authors":"Keliang Cen;Zheming Xing;Xuan Wang;Yadong Wang;Junyi Li","doi":"10.1109/TCBB.2024.3488281","DOIUrl":"10.1109/TCBB.2024.3488281","url":null,"abstract":"Investigating the associations between circRNA and diseases is vital for comprehending the underlying mechanisms of diseases and formulating effective therapies. Computational prediction methods often rely solely on known circRNA-disease data, indirectly incorporating other biomolecules' effects by computing circRNA and disease similarities based on these molecules. However, this approach is limited, as other biomolecules also play significant roles in circRNA-disease interactions. To address this, we construct a comprehensive heterogeneous network incorporating data on human circRNAs, diseases, and other biomolecule interactions to develop a novel computational model, circ2DGNN, which is built upon a heterogeneous graph neural network. circ2DGNN directly takes heterogeneous networks as inputs and obtains the embedded representation of each node for downstream link prediction through graph representation learning. circ2DGNN employs a Transformer-like architecture, which can compute heterogeneous attention score for each edge, and perform message propagation and aggregation, using a residual connection to enhance the representation vector. It uniquely applies the same parameter matrix only to identical meta-relationships, reflecting diverse parameter spaces for different relationship types. After fine-tuning hyperparameters via five-fold cross-validation, evaluation conducted on a test dataset shows circ2DGNN outperforms existing state-of-the-art(SOTA) methods.","PeriodicalId":13344,"journal":{"name":"IEEE/ACM Transactions on Computational Biology and Bioinformatics","volume":"21 6","pages":"2556-2567"},"PeriodicalIF":3.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discriminative Domain Adaption Network for Simultaneously Removing Batch Effects and Annotating Cell Types in Single-Cell RNA-Seq","authors":"Qi Zhu;Aizhen Li;Zheng Zhang;Chuhang Zheng;Junyong Zhao;Jin-Xing Liu;Daoqiang Zhang;Wei Shao","doi":"10.1109/TCBB.2024.3487574","DOIUrl":"10.1109/TCBB.2024.3487574","url":null,"abstract":"Machine learning techniques have become increasingly important in analyzing single-cell RNA and identifying cell types, providing valuable insights into cellular development and disease mechanisms. However, the presence of batch effects poses major challenges in scRNA-seq analysis due to data distribution variation across batches. Although several batch effect mitigation algorithms have been proposed, most of them focus only on the correlation of local structure embeddings, ignoring global distribution matching and discriminative feature representation in batch correction. In this paper, we proposed the discriminative domain adaption network (D2AN) for joint batch effects correction and type annotation with single-cell RNA-seq. Specifically, we first captured the global low-dimensional embeddings of samples from the source and target domains by adversarial domain adaption strategy. Second, a contrastive loss is developed to preliminarily align the source domain samples. Moreover, the semantic alignment of class centroids in the source and target domains is achieved for further local alignment. Finally, a self-paced learning mechanism based on inter-domain loss is adopted to gradually select samples with high similarity to the target domain for training, which is used to improve the robustness of the model. Experimental results demonstrated that the proposed method on multiple real datasets outperforms several state-of-the-art methods.","PeriodicalId":13344,"journal":{"name":"IEEE/ACM Transactions on Computational Biology and Bioinformatics","volume":"21 6","pages":"2543-2555"},"PeriodicalIF":3.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MLW-BFECF: A Multi-Weighted Dynamic Cascade Forest Based on Bilinear Feature Extraction for Predicting the Stage of Kidney Renal Clear Cell Carcinoma on Multi-Modal Gene Data","authors":"Liye Jia;Liancheng Jiang;Junhong Yue;Fang Hao;Yongfei Wu;Xilin Liu","doi":"10.1109/TCBB.2024.3486742","DOIUrl":"10.1109/TCBB.2024.3486742","url":null,"abstract":"The stage prediction of kidney renal clear cell carcinoma (KIRC) is important for the diagnosis, personalized treatment, and prognosis of patients. Many prediction methods have been proposed, but most of them are based on unimodal gene data, and their accuracy is difficult to further improve. Therefore, we propose a novel multi-weighted dynamic cascade forest based on the bilinear feature extraction (MLW-BFECF) model for stage prediction of KIRC using multimodal gene data (RNA-seq, CNA, and methylation). The proposed model utilizes a dynamic cascade framework with shuffle layers to prevent early degradation of the model. In each cascade layer, a voting technique based on three gene selection algorithms is first employed to effectively retain gene features more relevant to KIRC and eliminate redundant information in gene features. Then, two new bilinear models based on the gated attention mechanism are proposed to better extract new intra-modal and inter-modal gene features; Finally, based on the idea of the bagging, a multi-weighted ensemble forest classifiers module is proposed to extract and fuse probabilistic features of the three-modal gene data. A series of experiments demonstrate that the MLW-BFECF model based on the three-modal KIRC dataset achieves the highest prediction performance with an accuracy of 88.9 %.","PeriodicalId":13344,"journal":{"name":"IEEE/ACM Transactions on Computational Biology and Bioinformatics","volume":"21 6","pages":"2568-2579"},"PeriodicalIF":3.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An End-to-End Knowledge Graph Fused Graph Neural Network for Accurate Protein-Protein Interactions Prediction","authors":"Jie Yang;Yapeng Li;Guoyin Wang;Zhong Chen;Di Wu","doi":"10.1109/TCBB.2024.3486216","DOIUrl":"10.1109/TCBB.2024.3486216","url":null,"abstract":"Protein-protein interactions (PPIs) are essential to understanding cellular mechanisms, signaling networks, disease processes, and drug development, as they represent the physical contacts and functional associations between proteins. Recent advances have witnessed the achievements of artificial intelligence (AI) methods aimed at predicting PPIs. However, these approaches often handle the intricate web of relationships and mechanisms among proteins, drugs, diseases, ribonucleic acid (RNA), and protein structures in a fragmented or superficial manner. This is typically due to the limitations of non-end-to-end learning frameworks, which can lead to sub-optimal feature extraction and fusion, thereby compromising the prediction accuracy. To address these deficiencies, this paper introduces a novel end-to-end learning model, the Knowledge Graph Fused Graph Neural Network (KGF-GNN). This model comprises three integral components: (1) \u0000<bold>Protein Associated Network (PAN) Construction</b>\u0000: We begin by constructing a PAN that extensively captures the diverse relationships and mechanisms linking proteins with drugs, diseases, RNA, and protein structures. (2) \u0000<bold>Graph Neural Network for Feature Extraction</b>\u0000: A Graph Neural Network (GNN) is then employed to distill both topological and semantic features from the PAN, alongside another GNN designed to extract topological features directly from observed PPI networks. (3) \u0000<bold>Multi-layer Perceptron for Feature Fusion</b>\u0000: Finally, a multi-layer perceptron integrates these varied features through end-to-end learning, ensuring that the feature extraction and fusion processes are both comprehensive and optimized for PPI prediction. Extensive experiments conducted on real-world PPI datasets validate the effectiveness of our proposed KGF-GNN approach, which not only achieves high accuracy in predicting PPIs but also significantly surpasses existing state-of-the-art models. This work not only enhances our ability to predict PPIs with a higher precision but also contributes to the broader application of AI in Bioinformatics, offering profound implications for biological research and therapeutic development.","PeriodicalId":13344,"journal":{"name":"IEEE/ACM Transactions on Computational Biology and Bioinformatics","volume":"21 6","pages":"2518-2530"},"PeriodicalIF":3.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Evaluation Framework for Benchmarking Multi-Objective Feature Selection in Omics-Based Biomarker Discovery","authors":"Luca Cattelani;Arindam Ghosh;Teemu J. Rintala;Vittorio Fortino","doi":"10.1109/TCBB.2024.3480150","DOIUrl":"10.1109/TCBB.2024.3480150","url":null,"abstract":"Machine learning algorithms have been extensively used for accurate classification of cancer subtypes driven by gene expression-based biomarkers. However, biomarker models combining multiple gene expression signatures are often not reproducible in external validation datasets and their feature set size is often not optimized, jeopardizing their translatability into cost-effective clinical tools. We investigated how to solve the multi-objective problem of finding the best trade-offs between classification performance and set size applying seven algorithms for machine learning-driven feature subset selection and analyse how they perform in a benchmark with eight large-scale transcriptome datasets of cancer, covering both training and external validation sets. The benchmark includes evaluation metrics assessing the performance of the individual biomarkers and the solution sets, according to their accuracy, diversity, and stability of the composing genes. Moreover, a new evaluation metric for cross-validation studies is proposed that generalizes the hypervolume, which is commonly used to assess the performance of multi-objective optimization algorithms. Biomarkers exhibiting 0.8 of balanced accuracy on the external dataset for breast, kidney and ovarian cancer using respectively 4, 2 and 7 features, were obtained. Genetic algorithms often provided better performance than other considered algorithms, and the recently proposed NSGA2-CH and NSGA2-CHS were the best performing methods in most cases.","PeriodicalId":13344,"journal":{"name":"IEEE/ACM Transactions on Computational Biology and Bioinformatics","volume":"21 6","pages":"2432-2446"},"PeriodicalIF":3.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=10716353","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generative Biomedical Event Extraction With Constrained Decoding Strategy","authors":"Fangfang Su;Chong Teng;Fei Li;Bobo Li;Jun Zhou;Donghong Ji","doi":"10.1109/TCBB.2024.3480088","DOIUrl":"10.1109/TCBB.2024.3480088","url":null,"abstract":"Currently, biomedical event extraction has received considerable attention in various fields, including natural language processing, bioinformatics, and computational biomedicine. This has led to the emergence of numerous machine learning and deep learning models that have been proposed and applied to tackle this complex task. While existing models typically adopt an extraction-based approach, which requires breaking down the extraction of biomedical events into multiple subtasks for sequential processing, making it prone to cascading errors. This paper presents a novel approach by constructing a biomedical event generation model based on the framework of the pre-trained language model \u0000<italic>T5</i>\u0000. We employ a sequence-to-sequence generation paradigm to obtain events, the model utilizes constrained decoding algorithm to guide sequence generation, and a curriculum learning algorithm for efficient model learning. To demonstrate the effectiveness of our model, we evaluate it on two public benchmark datasets, Genia 2011 and Genia 2013. Our model achieves superior performance, illustrating the effectiveness of generative modeling of biomedical events.","PeriodicalId":13344,"journal":{"name":"IEEE/ACM Transactions on Computational Biology and Bioinformatics","volume":"21 6","pages":"2471-2484"},"PeriodicalIF":3.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guest Editors' Introduction to the Special Section on Bioinformatics Research and Applications","authors":"Zhipeng Cai;Alexander Zelikovsky","doi":"10.1109/TCBB.2024.3390374","DOIUrl":"https://doi.org/10.1109/TCBB.2024.3390374","url":null,"abstract":"","PeriodicalId":13344,"journal":{"name":"IEEE/ACM Transactions on Computational Biology and Bioinformatics","volume":"21 5","pages":"1141-1142"},"PeriodicalIF":3.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=10712175","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142397043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"De Novo Drug Design by Multi-Objective Path Consistency Learning With Beam A* Search","authors":"Dengwei Zhao;Jingyuan Zhou;Shikui Tu;Lei Xu","doi":"10.1109/TCBB.2024.3477592","DOIUrl":"10.1109/TCBB.2024.3477592","url":null,"abstract":"Generating high-quality and drug-like molecules from scratch within the expansive chemical space presents a significant challenge in the field of drug discovery. In prior research, value-based reinforcement learning algorithms have been employed to generate molecules with multiple desired properties iteratively. The immediate reward was defined as the evaluation of intermediate-state molecules at each step, and the learning objective would be maximizing the expected cumulative evaluation scores for all molecules along the generative path. However, this definition of the reward was misleading, as in reality, the optimization target should be the evaluation score of only the final generated molecule. Furthermore, in previous works, randomness was introduced into the decision-making process, enabling the generation of diverse molecules but no longer pursuing the maximum future rewards. In this paper, immediate reward is defined as the improvement achieved through the modification of the molecule to maximize the evaluation score of the final generated molecule exclusively. Originating from the A\u0000<inline-formula><tex-math>$^*$</tex-math></inline-formula>\u0000 search, path consistency (PC), i.e., \u0000<inline-formula><tex-math>$f$</tex-math></inline-formula>\u0000 values on one optimal path should be identical, is employed as the objective function in the update of the \u0000<inline-formula><tex-math>$f$</tex-math></inline-formula>\u0000 value estimator to train a multi-objective \u0000<i>de novo</i>\u0000 drug designer. By incorporating the \u0000<inline-formula><tex-math>$f$</tex-math></inline-formula>\u0000 value into the decision-making process of beam search, the DrugBA\u0000<inline-formula><tex-math>$^*$</tex-math></inline-formula>\u0000 algorithm is proposed to enable the large-scale generation of molecules that exhibit both high quality and diversity. Experimental results demonstrate a substantial enhancement over the state-of-the-art algorithm QADD in multiple molecular properties of the generated molecules.","PeriodicalId":13344,"journal":{"name":"IEEE/ACM Transactions on Computational Biology and Bioinformatics","volume":"21 6","pages":"2459-2470"},"PeriodicalIF":3.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orientation Determination of Cryo-EM Projection Images Using Reliable Common Lines and Spherical Embeddings","authors":"Xiangwen Wang;Qiaoying Jin;Li Zou;Xianghong Lin;Yonggang Lu","doi":"10.1109/TCBB.2024.3476619","DOIUrl":"10.1109/TCBB.2024.3476619","url":null,"abstract":"Three-dimensional (3D) reconstruction in single-particle cryo-electron microscopy (cryo-EM) is a critical technique for recovering and studying the fine 3D structure of proteins and other biological macromolecules, where the primary issue is to determine the orientations of projection images with high levels of noise. This paper proposes a method to determine the orientations of cryo-EM projection images using reliable common lines and spherical embeddings. First, the reliability of common lines between projection images is evaluated using a weighted voting algorithm based on an iterative improvement technique and binarized weighting. Then, the reliable common lines are used to calculate the normal vectors and local \u0000<inline-formula><tex-math>$X$</tex-math></inline-formula>\u0000-axis vectors of projection images after two spherical embeddings. Finally, the orientations of projection images are determined by aligning the results of the two spherical embeddings using an orthogonal constraint. Experimental results on both synthetic and real cryo-EM projection image datasets demonstrate that the proposed method can achieve higher accuracy in estimating the orientations of projection images and higher resolution in reconstructing preliminary 3D structures than some common line-based methods, indicating that the proposed method is effective in single-particle cryo-EM 3D reconstruction.","PeriodicalId":13344,"journal":{"name":"IEEE/ACM Transactions on Computational Biology and Bioinformatics","volume":"21 6","pages":"2496-2509"},"PeriodicalIF":3.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}