Viruses exert a profound influence on both human health and the global ecosystem, yet they remain largely unexplored. Precise taxonomic classification of viral sequences is essential for discovering novel viruses, elucidating their functions, and assessing their implications for public health and environmental monitoring. Traditional taxonomy methods based on genome references are limited by the vast number of unexplored viruses, rapid mutation rates, and high genetic diversity. Additionally, highly imbalanced species distribution and significant variances in inter-species genomic distances across taxonomic units pose challenges to classifier training. Conceptualizing genomic sequences as sentences in a natural language, large language models provide novel approaches for extracting intrinsic viral genome characteristics. In this study, we introduce ViTax, a virus taxonomy classification tool powered by HyenaDNA, a large language foundation model for long-range genomic sequences at single nucleotide resolution. ViTax integrates supervised prototypical contrastive learning to address the highly imbalanced distributions across various taxonomic clades and demonstrates superior performance to current leading methods in virus taxonomy, particularly significant for long sequences. Moreover, ViTax designs a belief mapping tree using the Lowest Common Ancestor algorithm to adaptively assign a sequence to the lowest taxonomy clade with confidence. For the open-set problem, where sequences belong to novel and unexplored genera, ViTax can adaptively assign them to a higher level of known taxonomy with outstanding performance. These capabilities make ViTax a robust tool for advancing the accuracy and reliability of viral taxonomy classification. The code is available at https://github.com/Ying-Lab/ViTax.

Accumulating evidence indicates that microRNAs (miRNAs) can control and coordinate various biological processes. Consequently, abnormal expressions of miRNAs have been linked to various complex diseases. Recognizable proof of miRNA-disease associations (MDAs) will contribute to the diagnosis and treatment of human diseases. Nevertheless, traditional experimental verification of MDAs is laborious and limited to small-scale. Therefore, it is necessary to develop reliable and effective computational methods to predict novel MDAs. In this work, a multi-kernel graph attention deep autoencoder (MGADAE) method is proposed to predict potential MDAs. In detail, MGADAE first employs the multiple kernel learning (MKL) algorithm to construct an integrated miRNA similarity and disease similarity, providing more biological information for further feature learning. Second, MGADAE combines the known MDAs, disease similarity, and miRNA similarity into a heterogeneous network, then learns the representations of miRNAs and diseases through graph convolution operation. After that, an attention mechanism is introduced into MGADAE to integrate the representations from multiple graph convolutional network (GCN) layers. Lastly, the integrated representations of miRNAs and diseases are input into the bilinear decoder to obtain the final predicted association scores. Corresponding experiments prove that the proposed method outperforms existing advanced approaches in MDA prediction. Furthermore, case studies related to two human cancers provide further confirmation of the reliability of MGADAE in practice.

With the development of bioinformatics, the important role played by lncRNAs in various intractable diseases has aroused the interest of many experts. In recent studies, researchers have found that several human diseases are related to lncRANs. Moreover, it is very difficult and expensive to explore the unknown lncRNA-disease associations (LDAs), so only a few associations have been confirmed. It is vital to find a more accurate and effective method to identify potential LDAs. In this study, a method of collaborative matrix factorization based on correntropy (LDCMFC) is proposed for the identification of potential LDAs. To improve the robustness of the algorithm, the traditional minimization of the Euclidean distance is replaced with the maximized correntropy. In addition, the weighted K nearest known neighbor (WKNKN) method is used to rebuild the adjacency matrix. Finally, the performance of LDCMFC is tested by 5-fold cross-validation. Compared with other traditional methods, LDACMFC obtains a higher AUC of 0.8628. In different types of studies of three important cancer cases, most of the potentially relevant lncRNAs derived from the experiments have been validated in the databases. The final result shows that LDCMFC is a feasible method to predict LDAs.

MicroRNAs (miRNAs) are single-stranded small RNAs. An increasing number of studies have shown that miRNAs play a vital role in many important biological processes. However, some experimental methods to predict unknown miRNA-disease associations (MDAs) are time-consuming and costly. Only a small percentage of MDAs are verified by researchers. Therefore, there is a great need for high-speed and efficient methods to predict novel MDAs. In this paper, a new computational method based on Dual-Network Information Fusion (DNIF) is developed to predict potential MDAs. Specifically, on the one hand, two enhanced sub-models are integrated to reconstruct an effective prediction framework; on the other hand, the prediction performance of the algorithm is improved by fully fusing multiple omics data information, including validated miRNA-disease associations network, miRNA functional similarity, disease semantic similarity and Gaussian interaction profile (GIP) kernel network associations. As a result, DNIF achieves the excellent performance under situation of 5-fold cross validation (average AUC of 0.9571). In the cases study of three important human diseases, our model has achieved satisfactory performance in predicting potential miRNAs for certain diseases. The reliable experimental results demonstrate that DNIF could serve as an effective calculation method to accelerate the identification of MDAs.

Determining microRNA (miRNA)-disease associations (MDAs) is an integral part in the prevention, diagnosis, and treatment of complex diseases. However, wet experiments to discern MDAs are inefficient and expensive. Hence, the development of reliable and efficient data integrative models for predicting MDAs is of significant meaning. In the present work, a novel deep learning method for predicting MDAs through deep autoencoder with multiple kernel learning (DAEMKL) is presented. Above all, DAEMKL applies multiple kernel learning (MKL) in miRNA space and disease space to construct miRNA similarity network and disease similarity network, respectively. Then, for each disease or miRNA, its feature representation is learned from the miRNA similarity network and disease similarity network via the regression model. After that, the integrated miRNA feature representation and disease feature representation are input into deep autoencoder (DAE). Furthermore, the novel MDAs are predicted through reconstruction error. Ultimately, the AUC results show that DAEMKL achieves outstanding performance. In addition, case studies of three complex diseases further prove that DAEMKL has excellent predictive performance and can discover a large number of underlying MDAs. On the whole, our method DAEMKL is an effective method to identify MDAs.

With the development of research on the complex aetiology of many diseases, computational drug repositioning methodology has proven to be a shortcut to costly and inefficient traditional methods. Therefore, developing more promising computational methods is indispensable for finding new candidate diseases to treat with existing drugs. In this paper, a model integrating a new variant of message passing neural network and a novel-gated fusion mechanism called GLGMPNN is proposed for drug-disease association prediction. First, a light-gated message passing neural network (LGMPNN), including message passing, aggregation and updating, is proposed to separately extract multiple pieces of information from the similarity networks and the association network. Then, a gated fusion mechanism consisting of a forget gate and an output gate is applied to integrate the multiple pieces of information to extent. The forget gate calculated by the multiple embeddings is built to integrate the association information into the similarity information. Furthermore, the final node representations are controlled by the output gate, which fuses the topology information of the networks and the initial similarity information. Finally, a bilinear decoder is adopted to reconstruct an adjacency matrix for drug-disease associations. Evaluated by 10-fold cross-validations, GLGMPNN achieves excellent performance compared with the current models. The following studies show that our model can effectively discover novel drug-disease associations.

BACKGROUND: With the rapid development of various advanced biotechnologies, researchers in related fields have realized that microRNAs (miRNAs) play critical roles in many serious human diseases. However, experimental identification of new miRNA-disease associations (MDAs) is expensive and time-consuming. Practitioners have shown growing interest in methods for predicting potential MDAs. In recent years, an increasing number of computational methods for predicting novel MDAs have been developed, making a huge contribution to the research of human diseases and saving considerable time. In this paper, we proposed an efficient computational method, named bipartite graph-based collaborative matrix factorization (BGCMF), which is highly advantageous for predicting novel MDAs. RESULTS: By combining two improved recommendation methods, a new model for predicting MDAs is generated. Based on the idea that some new miRNAs and diseases do not have any associations, we adopt the bipartite graph based on the collaborative matrix factorization method to complete the prediction. The BGCMF achieves a desirable result, with AUC of up to 0.9514 ± (0.0007) in the five-fold cross-validation experiments. CONCLUSIONS: Five-fold cross-validation is used to evaluate the capabilities of our method. Simulation experiments are implemented to predict new MDAs. More importantly, the AUC value of our method is higher than those of some state-of-the-art methods. Finally, many associations between new miRNAs and new diseases are successfully predicted by performing simulation experiments, indicating that BGCMF is a useful method to predict more potential miRNAs with roles in various diseases.