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mmContext: an open framework for multimodal contrastive learning of omics and text data.

SUMMARY: Multimodal approaches are increasingly leveraged for integrating omics data with textual biological knowledge. Yet there is still no accessible, standardized framework that enables systematic comparison of omics representations with different text encoders within a unified workflow. We present mmContext, a lightweight and extensible multimodal embedding framework built on top of the open-source Sentence Transformers library. The software allows researchers to train or apply models that jointly embed omics and text data using any numeric representation stored in an AnnData.obsm layer and any text encoder available in Hugging Face. mmContext supports integration of diverse biological text sources and provides pipelines for training, evaluation, and data preparation. We train and evaluate models for a RNA-Seq and text integration task, and demonstrate their utility through zero-shot classification of cell types and diseases across four independent datasets. By releasing all models, datasets, and tutorials openly, mmContext enables reproducible and accessible multimodal learning for omics-text integration. AVAILABILITY AND IMPLEMENTATION: Pretrained checkpoints and full source code for our custom MMContextEncoder are available on Hugging Face huggingface.co/jo-mengr. The Python package github.com/mengerj/mmcontext provides the model implementation and training and evaluation scripts for custom training. The releases for the publication can be accessed via zenodo: adata_hf_datasets: doi.org/10.5281/zenodo.19185217 and mmContext: doi.org/10.5281/zenodo.19185493.

Computational Biology

Integrating histology and spatial transcriptomics via multimodal transformers and contrastive representation learning for accurate gene expression prediction.

Predicting spatial gene expression from Histological images is a fundamental task in understanding tissue organization and molecular phenotypes. However, existing methods often rely on single-model representations or lack effective alignment between image and transcriptomic features. To address these limitations, we propose a unified multimodal learning framework that integrates histological imaging and spatial transcriptomics through a shared latent representation space. Specifically, histological H&E images are encoded by a ResNet50-based convolutional stem and a MobileViT Transformer backbone to extract hierarchical visual representations. Both modalities are projected into a shared latent space via linear-GELU-dropout transformation blocks, enabling cross-modal alignment through a contrastive learning objective that maximizes agreement between the corresponding image and the spot embeddings. Experimental results on the 10x Genomics Visium dataset of human liver tissue demonstrate that MViTGene achieves significantly higher prediction accuracy than existing methods across multiple gene subsets, with improvements of 20%, 33%, and 12% in predicting marker genes, highly expressed genes, and highly variable genes, respectively. The significant improvement in relevance indicates that the model can more accurately capture the true correspondence between tissue morphology and gene expression, therefore enabling more reliable biological interpretation. It provides a computational tool for high-throughput spatial gene expression prediction that balances performance and interpretability.

Humans

Multimodal alignment improves generalizability of genomic biomarker prediction in computational pathology.

Computational pathology models that use digitized histopathology whole-slide images have the potential to become a cost-effective and scalable alternative to molecular assays for the prediction of genomic biomarkers, a key task in precision oncology. However, as new genomic biomarkers are discovered or quantified, large, labeled datasets must be prospectively collected to train new models. To address this challenge, we developed multimodal alignment for biomarker learning and generalization (MARBLE), a multimodal contrastive pretraining strategy that integrates structured biomarker knowledge into representation learning of histopathology images. MARBLE aligns histopathology-derived representations with representations of genomic biomarkers generated by a large language model (LLM) and a protein language model (PLM). This biologically informed alignment enables data-efficient generalization to novel, out-of-distribution biomarkers. Using the MSK-IMPACT cohort of over 40,000 patients across multiple biomarker panel versions, we design experiments grounded in real-world data to demonstrate the value of our proposed approach.

CP: computational biology

Survival prediction for clear cell renal cell carcinoma based on deep multimodal synergistic survival network.

Objective.To propose a deep multimodal synergistic survival analysis framework (Deep Multimodal Synergistic Survival Network, DMSSN) to achieve accurate prognostic analysis for clear cell renal cell carcinoma (ccRCC).Methods.This study (DMSSN) utilized matched multimodal data from the Cancer Genome Atlas-KIRC database, including CT imaging data, whole slide images, copy number variation (CNV) features, and clinical data. Deep Canonical Correlation Analysis was employed to map heterogeneous modalities into a shared latent space. Contrastive learning was introduced to enhance semantic consistency across multimodal features, and a gating network was utilized for the adaptive fusion of multimodal information to achieve precise survival risk prediction for patients.Results.Experimental results demonstrated that DMSSN achieved a Concordance Index (C-index) of 0.8153 ± 0.0994, with a Log-rank testp-value of 1.6553×10-11. DMSSN exhibited significant performance advantages over traditional statistical methods like Log-rank-Cox (0.7055 ± 0.0670) and machine learning methods such as Random Survival Forest (RSF) (0.6836 ± 0.1048). Furthermore, in comparison with similar deep learning approaches, DMSSN outperformed late fusion strategies (0.7493 ± 0.1211) and discrete-time survival models such as DeepHit (0.7655 ± 0.1041) and Nnet-surv (0.7694 ± 0.0635). Notably, DMSSN still achieved the best predictive performance when compared to the classic deep survival model DeepSurv (0.7919 ± 0.0978) and advanced state-of-the-art multimodal fusion frameworks like Context-Aware Transformer (0.7735 ± 0.0818) and Multimodal Co-Attention Transformer (0.8102 ± 0.0972). Ablation studies showed that removing any single modality led to a decline in performance, with the largest numerical decrease occurring after removing CT imaging features (C-index decreased to 0.7327), validating the complementarity of multimodal data and the pivotal role of radiomic features in prognostic assessment. Module ablation experiments further confirmed the effectiveness of the core components.Conclusion:By effectively integrating imaging, pathology, genomic, and clinical features, the DMSSN framework demonstrates superior performance and robustness in the survival prediction of ccRCC.

Carcinoma, Renal Cell

A Graph Contrastive Learning Method for Enhancing Genome Recovery in Complex Microbial Communities.

Accurate genome binning is essential for resolving microbial community structure and functional potential from metagenomic data. However, existing approaches-primarily reliant on tetranucleotide frequency (TNF) and abundance profiles-often perform sub-optimally in the face of complex community compositions, low-abundance taxa, and long-read sequencing datasets. To address these limitations, we present MBGCCA, a novel metagenomic binning framework that synergistically integrates graph neural networks (GNNs), contrastive learning, and information-theoretic regularization to enhance binning accuracy, robustness, and biological coherence. MBGCCA operates in two stages: (1) multimodal information integration, where TNF and abundance profiles are fused via a deep neural network trained using a multi-view contrastive loss, and (2) self-supervised graph representation learning, which leverages assembly graph topology to refine contig embeddings. The contrastive learning objective follows the InfoMax principle by maximizing mutual information across augmented views and modalities, encouraging the model to extract globally consistent and high-information representations. By aligning perturbed graph views while preserving topological structure, MBGCCA effectively captures both global genomic characteristics and local contig relationships. Comprehensive evaluations using both synthetic and real-world datasets-including wastewater and soil microbiomes-demonstrate that MBGCCA consistently outperforms state-of-the-art binning methods, particularly in challenging scenarios marked by sparse data and high community complexity. These results highlight the value of entropy-aware, topology-preserving learning for advancing metagenomic genome reconstruction.

canonical correlation analysis

Artificial intelligence (AI) uses in stereotactic radiosurgery (SRS): diagnosis with brain metastasis (BM) - A systematic review.

BACKGROUND: Brain metastases (BM) are the most common intracranial tumors in adults, and stereotactic radiosurgery (SRS) has become a mainstay of management. However, several diagnostic challenges persist in the SRS pathway, particularly the differentiation of radiation necrosis (RN) from true tumor progression, which conventional MRI and even advanced imaging techniques often cannot reliably resolve. Recent advances in artificial intelligence (AI) offer the potential to address these diagnostic limitations. This systematic review synthesizes current literature on AI applications for MRI-based diagnostic decision support in BM patients undergoing SRS, with a focus on radiomics and deep learning tools for distinguishing RN from progression, classifying molecular and histologic subtypes, and predicting treatment response. METHODS: A systematic review was performed in accordance with PRISMA guidelines. PubMed, Web of Science, and Scopus were searched using a targeted query combining terms related to AI, brain metastasis, diagnosis or imaging, and SRS. After screening 483 records and applying strict inclusion and exclusion criteria, 18 studies published between 2015 and 2025 were included. Data were extracted on study design, cohort characteristics, imaging modality, AI methodology, validation strategy, and reported diagnostic performance. RESULTS: Among the 18 included studies, AI models demonstrated strong performance across diagnostic tasks in the BM-SRS pathway. The differentiation of RN from true tumor progression was the most extensively studied application, addressed by 14 of 18 studies, with reported AUCs ranging from 0.71 to 0.94. Support vector machines, random-forest ensembles, convolutional neural networks, and transformer-based multimodal architectures were widely used. The literature evolved from single-sequence radiomic classifiers in 2018 to multimodal deep learning frameworks fusing imaging with clinical and genomic data in 2025. Contrast-enhanced T1-weighted MRI was the dominant imaging input, and texture-based radiomic features (GLCM, GLSZM, GLDM, and wavelet-derived features) were the most consistently predictive. The highest-performing models reached AUCs of 0.85-0.91 through multimodal integration of imaging with clinical and genomic features, and consistently outperformed expert neuroradiologist read on matched cases. Remaining studies addressed longitudinal segmentation-based detection of local failure and adverse radiation effects, BRAF mutation status in melanoma BM, early Gamma Knife treatment response, and primary tumor histology classification, with more variable performance. CONCLUSION: AI models, particularly those integrating MRI-derived radiomic features with clinical and genomic data, show high accuracy in supporting diagnostic decisions for BM patients treated with SRS. The post-SRS differentiation of radiation necrosis from true tumor progression has reached the greatest level of maturity and is closest to clinical translation, with potential to reduce unnecessary biopsies, personalize surveillance intervals, and rationalize treatment-pathway decisions. Other diagnostic applications, including molecular subtyping and primary tumor histology classification, remain exploratory and require further multicenter validation. Integration of AI tools into multidisciplinary tumor-board workflows, combined with prospective validation and standardized reporting, will be essential to realize the full clinical benefits of AI in SRS for brain metastases.

Humans

Scalable, generalizable and uncertainty-aware integration of spatial multiomics across diverse modalities and platforms with SCIGMA.

Recent advances in spatial omics technologies have enabled simultaneous profiling of transcriptomic, proteomic, epigenomic, metabolomic and imaging data at high spatial resolution, offering unprecedented opportunities to dissect tissue complexity. However, integrating these diverse and large-scale spatial multimodal datasets remains a major computational challenge. We present SCIGMA, a scalable and generalizable deep learning framework for spatial multiomics integration. SCIGMA introduces an uncertainty-aware contrastive learning objective and multiview graph neural networks to preserve modality-specific signals while learning biologically meaningful joint representations. Unlike previous methods, SCIGMA provides spatially resolved uncertainty estimates, interpretably identifying regions of biological or technical heterogeneity. SCIGMA supports integration of up to five modalities, and its modular framework is extensible to future technologies with even more modalities. It also scales to more than 1 million spatial locations, enabling analysis of high-resolution datasets such as Visium HD and Xenium Prime. We evaluated SCIGMA across 19 datasets spanning 8 modalities, 10 tissues and 9 platforms. On benchmarkable datasets, SCIGMA outperformed other methods in spatial domain detection, modality preservation, feature reconstruction and reproducibility. SCIGMA identifies biologically meaningful structures, refined spatial domains and modality-specific regulatory programs, providing a robust, flexible and future-ready solution for scalable spatial multimodal integration.

Multiomics

Breast Cancer Recurrence Status Assessment in 5 Years Using Multimodal Integrated Learning: A Feasibility Study.

Despite advances in breast cancer detection and treatment, recurrence after curative therapy continues to impact long-term survival and quality of life. Therefore, early identification of high-risk patients is crucial to guide personalized treatment and follow-up strategies. Although genomic assays provide valuable prognostic insights, their high cost and limited accessibility hinder widespread adoption in clinical practice. Recent machine learning or deep learning approaches leveraging clinical, imaging, or multimodal data have shown promise but do not reflect real-world clinical scenarios. This study proposes a deep learning-based multimodal framework for predicting 5-year breast cancer recurrence using routinely collected clinical data. The framework consists of three main components. First, we adopted automated tumor segmentation with MedSAM to extract the tumor region from ultrasound images. The radiomics features are extracted from those tumor regions. Second, report features are extracted using a Med-Contrastive Pre-trained Transformers (MedCPT)-based approach incorporating predefined, clinically informed queries. Third, a multimodal integration model jointly processes image, radiomics, clinical features, and report features through modality-specific branches. The image branch employs the Ultrasound Foundation Model (USFM) as the backbone, while structured tabular data is processed using the FT-Transformer architecture. The features of all branches are fused using a mixture-of-experts (MoE)-based classifier, and the entire model is trained using a progressive fusion training strategy. Experimental results confirm the feasibility of using ultrasound images with tumor mask integration for recurrence prediction and demonstrate the additive value of integrating multiple data modalities through the proposed multimodal integration model. The final model for recurrence prediction achieved an AUC of 0.7540, accuracy of 74.61%, sensitivity of 70.41%, and specificity of 76.44%. This feasibility study's findings underscore the potential of the proposed multimodal deep learning framework to provide accessible, accurate, and generalizable recurrence risk prediction using routinely available clinical data, potentially supporting more informed treatment decisions and personalized post-treatment monitoring in real-world clinical practice.

Breast cancer recurrence

Proprioception Training and Surrogate Outcomes: A Systematic Review of Definitions, Measures, and Effectiveness Claims.

BACKGROUND: "Proprioception training" is widely advocated in rehabilitation and sports practice, yet the term encompasses heterogeneous constructs, interventions, and outcomes. Many trials infer proprioceptive benefits from surrogate outcomes (balance, strength, or pain) rather than direct psychophysical indices. OBJECTIVE: We aimed to examine how proprioception is defined and measured, and how improvement is claimed, in randomized controlled trials. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020, PubMed, Scopus, and Web of Science were searched to October 2025. Eligible randomized controlled trials explicitly described interventions as "proprioceptive" or "sensorimotor training" and reported at least one proprioceptive outcome, either direct (e.g., joint position reproduction, threshold to detection of passive motion, active movement extent discrimination) or indirect (e.g., sway, balance). Methodological quality was appraised with the Physiotherapy Evidence Database (PEDro) scale and risk of bias using the Cochrane Risk of Bias 2 (RoB 2) tool. RESULTS: Fifty-one randomized controlled trials (n = 2319) were included. Comparative synthesis showed that improvements inferred from surrogate outcomes were more frequent and often larger than improvements observed in direct psychophysical measures. Directly targeted practice, angle specific, attentionally demanding, and aligned with the measured proprioceptive submodality and task construct, produced the most consistent benefits in position-reproduction accuracy/error, movement-detection sensitivity, or discrimination performance, depending on the outcome assessed. In contrast, multimodal regimens (balance, strengthening, taping, manual therapy) commonly improved balance, pain, strength, or function without comparably consistent evidence of enhanced direct psychophysical proprioceptive function. CONCLUSIONS: Specific psychophysical components of proprioceptive function appear modifiable, but only when training explicitly targets the sensory construct measured. The field remains conceptually diffuse, with frequent conflation of sensorimotor performance and proprioception. Progress depends on defining proprioceptive submodalities a priori, privileging validated psychophysical outcomes over surrogate outcomes, and aligning intervention content with measurement to substantiate true perceptual learning rather than generic motor adaptation.

Journal Article

Deep learning-based cross-attention fusion of multimodal MRI for survival prediction and risk stratification in IDH-wildtype glioblastoma: a multicenter study.

BACKGROUND: Glioblastoma (GBM) exhibits profound molecular and spatial heterogeneity, complicating prognostic evaluations. While multiparametric MRI provides crucial multidimensional biological information, conventional end-to-end deep learning integration strategies, such as early or late fusion, often fail to capture complex nonlinear cross-modal interactions. We aimed to systematically evaluate a cross-attention fusion (CAF) architecture for GBM survival prediction and quantify its incremental prognostic value relative to existing clinical tools. METHODS: In this multicenter retrospective study, 386 adults with IDH-wildtype, WHO grade 4 GBM were assembled from an institutional cohort (n = 226), the Chinese Glioma Genome Atlas (CGGA, n = 62), and The Cancer Genome Atlas (TCGA, n = 98). Using a unified 3D ResNet-18 backbone, we compared single-modality models, early fusion, late fusion, and CAF on preoperative T1-weighted, contrast-enhanced T1-weighted (T1CE), and T2-weighted MRI, and integrated the resulting deep learning risk score with routine clinical variables through multivariable Cox regression. Performance was assessed using Harrell's C-index, time-dependent AUC, and decision curve analysis. RESULTS: CAF showed numerically higher, more consistent C-index trends than early fusion, late fusion, and single-modality models (pooled C-index 0.629, 95% CI 0.594-0.664), although pairwise differences in time-dependent AUC were not statistically significant. Integrating clinical variables raised the pooled C-index to 0.691 (95% CI 0.660-0.721) in the treatment-era model, with comparable performance across the three cohorts (Local 0.688; CGGA 0.716; TCGA 0.689); a pre-treatment configuration excluding adjuvant therapy yielded a pooled C-index of 0.642. Under leave-one-cohort-out external validation, the combined model retained significant risk stratification in all held-out cohorts (C-index 0.63-0.71; all log-rank P&#xa0;<&#xa0;0.01), albeit with attenuated discrimination. The deep learning risk score remained independent after multivariable adjustment (HR 1.41 per SD, 95% CI 1.26-1.57; P&#xa0;<&#xa0;0.001). Kaplan-Meier analysis confirmed significant high- versus low-risk separation in all cohorts, and decision curve analysis showed greater net benefit than clinical-only and deep-learning-only models. CONCLUSION: The CAF-derived risk score offers prognostic information complementary to routine clinical variables, representing a promising noninvasive tool for individualized risk stratification when molecular profiling is incomplete or unavailable; these findings warrant prospective external validation before clinical use.

cross-attention fusion