Large Language Models (LLMs) hold significant promise for improving clinical decision support and reducing physician burnout by synthesizing complex, longitudinal cancer Electronic Health Records (EHRs). However, their implementation in this critical field faces three primary challenges: the inability to effectively process the extensive length and fragmented nature of patient records for accurate temporal analysis; a heightened risk of clinical hallucination, as conventional grounding techniques such as Retrieval-Augmented Generation (RAG) do not adequately incorporate process-oriented clinical guidelines; and unreliable evaluation metrics that hinder the validation of AI systems in oncology. To address these issues, we propose CliCARE, a framework for Grounding Large Language Models in Clinical Guidelines for Decision Support over Longitudinal Cancer Electronic Health Records. The framework operates by transforming unstructured, longitudinal EHRs into patient-specific Temporal Knowledge Graphs (TKGs) to capture long-range dependencies, and then grounding the decision support process by aligning these real-world patient trajectories with a normative guideline knowledge graph. This approach provides oncologists with evidence-grounded decision support by generating a high-fidelity clinical summary and an actionable recommendation. We validated our framework using large-scale, longitudinal data from a private Chinese cancer dataset and the public English MIMIC-IV dataset. In these settings, CliCARE significantly outperforms baselines, including leading long-context LLMs and Knowledge Graph-enhanced RAG methods. The clinical validity of our results is supported by a robust evaluation protocol, which demonstrates a high correlation with assessments made by oncologists.

Single-cell multi-omics technologies have revolutionized the study of cell states and functions by simultaneously profiling multiple molecular layers within individual cells. However, existing methods for integrating these data struggle to preserve critical feature information and fail to exploit known regulatory knowledge, which is essential for understanding cell functions. This limitation hinders their ability to provide comprehensive and accurate insights into cells. Here, we propose FactVAE, an innovative factorized variational autoencoder designed for the robust and accurate understanding of single-cell multi-omics data. FactVAE integrates the factorization principle into the variational autoencoder framework, ensuring the preservation of feature information while leveraging the non-linear capture of sample information by neural networks. Additionally, known regulatory knowledge is incorporated during model training, and a knowledge transfer strategy is employed for cell embedding optimization and data augmentation. Comparative analyses of single-cell multi-omics datasets from different protocols and the spatial multi-omics dataset demonstrate that FactVAE not only outperforms benchmark methods in clustering performance but also generates augmented data that reveals the clearest cell-type-specific motif expression. Moreover, the feature embeddings captured by FactVAE enable the inference of potential and reliable gene regulatory relationships. Overall, FactVAE's superior performance and strong scalability make it a promising new solution for single-cell multi-omics data analysis.

Dimensionality reduction and clustering are crucial tasks in single-cell RNA sequencing (scRNA-seq) data analysis, treated independently in the current process, hindering their mutual benefits. The latest methods jointly optimize these tasks through deep clustering. However, contrastive learning, with powerful representation capability, can bridge the gap that common deep clustering methods face, which requires pre-defined cluster centers. Therefore, a dual-level contrastive clustering method with nonuniform sampling (nsDCC) is proposed for scRNA-seq data analysis. Dual-level contrastive clustering, which combines instance-level contrast and cluster-level contrast, jointly optimizes dimensionality reduction and clustering. Multi-positive contrastive learning and unit matrix constraint are introduced in instance- and cluster-level contrast, respectively. Furthermore, the attention mechanism is introduced to capture inter-cellular information, which is beneficial for clustering. The nsDCC focuses on important samples at category boundaries and in minority categories by the proposed nearest boundary sparsest density weight assignment algorithm, making it capable of capturing comprehensive characteristics against imbalanced datasets. Experimental results show that nsDCC outperforms the six other state-of-the-art methods on both real and simulated scRNA-seq data, validating its performance on dimensionality reduction and clustering of scRNA-seq data, especially for imbalanced data. Simulation experiments demonstrate that nsDCC is insensitive to "dropout events" in scRNA-seq. Finally, cluster differential expressed gene analysis confirms the meaningfulness of results from nsDCC. In summary, nsDCC is a new way of analyzing and understanding scRNA-seq data.

BACKGROUND: In the field of genomics and personalized medicine, it is a key issue to find biomarkers directly related to the diagnosis of specific diseases from high-throughput gene microarray data. Feature selection technology can discover biomarkers with disease classification information. RESULTS: We use support vector machines as classifiers and use the five-fold cross-validation average classification accuracy, recall, precision and F1 score as evaluation metrics to evaluate the identified biomarkers. Experimental results show classification accuracy above 0.93, recall above 0.92, precision above 0.91, and F1 score above 0.94 on eight microarray datasets. METHOD: This paper proposes a two-stage hybrid biomarker selection method based on ensemble filter and binary differential evolution incorporating binary African vultures optimization (EF-BDBA), which can effectively reduce the dimension of microarray data and obtain optimal biomarkers. In the first stage, we propose an ensemble filter feature selection method. The method combines an improved fast correlation-based filter algorithm with Fisher score. obviously redundant and irrelevant features can be filtered out to initially reduce the dimensionality of the microarray data. In the second stage, the optimal feature subset is selected using an improved binary differential evolution incorporating an improved binary African vultures optimization algorithm. The African vultures optimization algorithm has excellent global optimization ability. It has not been systematically applied to feature selection problems, especially for gene microarray data. We combine it with a differential evolution algorithm to improve population diversity. CONCLUSION: Compared with traditional feature selection methods and advanced hybrid methods, the proposed method achieves higher classification accuracy and identifies excellent biomarkers while retaining fewer features. The experimental results demonstrate the effectiveness and advancement of our proposed algorithmic model.

Obtaining essential genes from microarray data that can diagnose diseases can be very useful for researchers to understand diseases and develop drugs. However, the high computational cost due to the “curse of dimensionality” and the high redundancy among features limit the application of evolutionary algorithms to the feature selection problem for high-dimensional data. This paper proposes a two-stage hybrid feature selection method to address this problem. In the first stage, a simple and efficient filtering me thod is used to initially filter redundant features, reduce the feature dimensionality, and reduce the search space of the evolutionary algorithm in the second stage. In the second stage, we propose an improved differential evolution algorithm. We redesign the binary quantization of the differential evolution algorithm for the characteristics of microarray data and improve the algorithm’s variation process to balance the algorithm’s search efficiency and accuracy. In addition, we define the redundancy of feature subsets and add it to the fitness function to reduce the redundancy of the final feature subsets. The proposed method is compared with classical feature selection methods and advanced hybrid feature selection methods on eight publicly available microarray data, and the effectiveness and advancement of the proposed method are demonstrated.

The discovery of diagnostically significant genes from microarray data is essential for disease diagnosis and drug research. However, the difficulty of analyzing microarray data comes from its high dimensionality and small sample size. Feature selection can effectively remove irrelevant and redundant features, reduce data dimensionality, and improve the accuracy of classifiers. This paper proposes a two-stage hybrid feature selection method MMBDE based on the improved min-Redundancy and Max-Relevance (mRMR) and the improved Binary Differential Evolution (BDE) algorithm. The improved mRMR is used to reduce the feature dimensionality at a coarse-scale significantly. In contrast, the improved BDE is used to refine the feature dimensionality at fine-scale further and select the best features. The experimental results show that MMBDE successfully reduces the dimensionality of microarray gene expression data, obtains high classification accuracy, and extracts effective features closely related to diseases from microarray gene expression data. The relevant datasets and codes can be obtained from https://github.com/xwdshiwo/MMBDE.

BACKGROUND: Finding significant genes or proteins from gene chip data for disease diagnosis and drug development is an important task. However, the challenge comes from the curse of the data dimension. It is of great significance to use machine learning methods to find important features from the data and build an accurate classification model. RESULTS: The proposed method has proved superior to the published advanced hybrid feature selection method and traditional feature selection method on different public microarray data sets. In addition, the biomarkers selected using our method show a match to those provided by the cooperative hospital in a set of clinical cleft lip and palate data. METHOD: In this paper, a feature selection algorithm ILRC based on clustering and improved L1 regularization is proposed. The features are firstly clustered, and the redundant features in the sub-clusters are deleted. Then all the remaining features are iteratively evaluated using ILR. The final result is given according to the cumulative weight reordering. CONCLUSION: The proposed method can effectively remove redundant features. The algorithm's output has high stability and classification accuracy, which can potentially select potential biomarkers.