Multimodal large language models (MLLMs) can process and integrate information from multimodality sources, such as text and images. However, interrelationship among input modalities, uncertainties due to individual uni-modal data and potential clinical applications following such an uncertainty decomposition are yet fully understood in the context of large-scale MLLMs. In this work, we propose a multimodal uncertainty propagation model (MUPM) based on uncertainty propagation, to characterise the relationship among the uncertainties arising from image-only, text-only, and joint image-text variations in MLLM inputs. Using real clinical data consisting of cardiac MR scans and digital health records, we describe that MUPMs can be optimised robustly with a few samples. We then show that the fitted MUPMs are generalisable across different input data distributions and, perhaps surprisingly, across different downstream tasks. Such a transferability may be explained by the shared pretraining, comparatively light MLLM fine-tuning, along with the low-dimensional nature of the MUPMs. More importantly, this learned transferability, quantifying the relationship between these uncertainties, led to direct clinical applications in which uncertainties may be estimated and thus analysed robustly for varying data or even a novel set of cardiac disease prediction tasks. In addition, we show experimentally the efficiency in multimodal data required for estimating the overall uncertainty and its ability to identify redundant factors, both of which are considered practical yet clinically useful applications with the proposed MUPMs. Codes are available at https://github.com/yucheng722/MUPM.
Chronic diseases are long-term, manageable, yet typically incurable conditions, highlighting the need for effective preventive strategies. Machine learning has been widely used to assess individual risk for chronic diseases. However, many models rely on medical test data (e.g. blood results, glucose levels), which limits their utility for proactive self-assessment. Additionally, to gain public trust, machine learning models should be explainable and transparent. Although some research on self-assessment machine learning models includes explainability, their explanations are not validated against established medical literature, reducing confidence in their reliability. To address these issues, we develop deep learning models that predict the risk of developing 13 chronic diseases using only personal and lifestyle factors, enabling accessible, self-directed preventive care. Importantly, we use SHAP-based explainability to identify the most influential model features and validate them against established medical literature. Our results show a strong alignment between the models' most influential features and established medical literature, reinforcing the models' trustworthiness. Critically, we find that this observation holds across 13 distinct diseases, indicating that this machine learning approach can be broadly trusted for chronic disease prediction. This work lays the foundation for developing trustworthy machine learning tools for self-directed preventive care. Future research can explore other approaches for models' trustworthiness and discuss how the models can be used ethically and responsibly.
Disease-symptom datasets are significant and in demand for medical research, disease diagnosis, clinical decision-making, and AI-driven health management applications. These datasets help identify symptom patterns associated with specific diseases, thus improving diagnostic accuracy and enabling early detection. The dataset presented in this study systematically compiles disease-symptom relationships from various online sources, medical literature, and publicly available health databases. The data was gathered through analyzing peer-reviewed medical articles, clinical case studies, and disease-symptom association reports. Only the verified medical sources were included in the dataset, while those from non-peer-reviewed and anecdotal sources were excluded. The dataset is structured in a tabular format, where the first column represents diseases, and the remaining columns represent symptoms. Each symptom cell contains a binary value (1 or 0), indicating whether a symptom is associated with a disease (1 for presence, 0 for absence). Thereby, this structured representation makes the dataset very useful for a wide range of applications, including machine learning-based disease prediction, clinical decision support systems, and epidemiological studies. Although there are some advancements in the field of disease-symptom datasets, there is a significant gap in structured datasets for the Bangla language. This dataset aims to bridge that gap by facilitating the development of multilingual medical informatics tools and improving disease prediction models for underrepresented linguistic communities. Further developments should include region-specific diseases and further fine-tuning of symptom associations for better diagnostic performance
Alzheimer's disease (AD) dementia is the most common form of dementia. With the emergence of disease-modifying therapies, predicting disease risk before symptom onset has become critical. We introduce DuAL-Net, a hybrid deep learning framework for AD dementia prediction using whole genome sequencing (WGS) data. DuAL-Net integrates two components: local probability modeling, which segments the genome into non-overlapping windows, and global annotation-based modeling, which annotates SNPs and reorganizes WGS input to capture long-range functional relationships. Both employ out-of-fold stacking with TabNet and Random Forest classifiers. Final predictions combine local and global probabilities using an optimized weighting parameter alpha. We analyzed WGS data from 1,050 individuals (443 cognitively normal, 607 AD dementia) using five-fold cross-validation. DuAL-Net achieved an AUC of 0.671 using top-ranked SNPs, representing 35.0% and 20.3% higher performance than bottom-ranked and randomly selected SNPs, respectively. ROC analysis demonstrated strong positive correlation between SNP prioritization rank and predictive power. The model identified known AD-associated SNPs as top contributors alongside potentially novel variants. DuAL-Net presents a promising framework improving both predictive accuracy and biological interpretability. The framework and web implementation offer an accessible platform for broader research applications.
Deep learning models have shown strong performance in classifying Alzheimer's disease (AD) from R2* maps, but their decision-making remains opaque, raising concerns about interpretability. Previous studies suggest biases in model decisions, necessitating further analysis. This study uses Layer-wise Relevance Propagation (LRP) and spectral clustering to explore classifier decision strategies across preprocessing and training configurations using R2* maps. We trained a 3D convolutional neural network on R2* maps, generating relevance heatmaps via LRP and applied spectral clustering to identify dominant patterns. t-Stochastic Neighbor Embedding (t-SNE) visualization was used to assess clustering structure. Spectral clustering revealed distinct decision patterns, with the relevance-guided model showing the clearest separation between AD and normal control (NC) cases. The t-SNE visualization confirmed that this model aligned heatmap groupings with the underlying subject groups. Our findings highlight the significant impact of preprocessing and training choices on deep learning models trained on R2* maps, even with similar performance metrics. Spectral clustering offers a structured method to identify classification strategy differences, emphasizing the importance of explainability in medical AI.
Modelling disease progression in precision medicine requires capturing complex spatio-temporal dynamics while preserving anatomical integrity. Existing methods often struggle with longitudinal dependencies and structural consistency in progressive disorders. To address these limitations, we introduce MambaControl, a novel framework that integrates selective state-space modelling with diffusion processes for high-fidelity prediction of medical image trajectories. To better capture subtle structural changes over time while maintaining anatomical consistency, MambaControl combines Mamba-based long-range modelling with graph-guided anatomical control to more effectively represent anatomical correlations. Furthermore, we introduce Fourier-enhanced spectral graph representations to capture spatial coherence and multiscale detail, enabling MambaControl to achieve state-of-the-art performance in Alzheimer's disease prediction. Quantitative and regional evaluations demonstrate improved progression prediction quality and anatomical fidelity, highlighting its potential for personalised prognosis and clinical decision support.
This study presents a machine learning-based framework for heart disease prediction using the heart-disease dataset, comprising 303 samples with 14 features. The methodology involves data preprocessing, model training, and evaluation using three classifiers: Logistic Regression, K-Nearest Neighbors (KNN), and Random Forest. Hyperparameter tuning with GridSearchCV and RandomizedSearchCV was employed to enhance model performance. The Random Forest classifier outperformed other models, achieving an accuracy of 91% and an F1-score of 0.89. Evaluation metrics, including precision, recall, and confusion matrix, revealed balanced performance across classes. The proposed model demonstrates strong potential for aiding clinical decision-making by effectively predicting heart disease. Limitations such as dataset size and generalizability underscore the need for future studies using larger and more diverse datasets. This work highlights the utility of machine learning in healthcare, offering insights for further advancements in predictive diagnostics.
Medical disease prediction, particularly through imaging, remains a challenging task due to the complexity and variability of medical data, including noise, ambiguity, and differing image quality. Recent deep learning models, including Knowledge Distillation (KD) methods, have shown promising results in brain tumor image identification but still face limitations in handling uncertainty and generalizing across diverse medical conditions. Traditional KD methods often rely on a context-unaware temperature parameter to soften teacher model predictions, which does not adapt effectively to varying uncertainty levels present in medical images. To address this issue, we propose a novel framework that integrates Ant Colony Optimization (ACO) for optimal teacher-student model selection and a novel context-aware predictor approach for temperature scaling. The proposed context-aware framework adjusts the temperature based on factors such as image quality, disease complexity, and teacher model confidence, allowing for more robust knowledge transfer. Additionally, ACO efficiently selects the most appropriate teacher-student model pair from a set of pre-trained models, outperforming current optimization methods by exploring a broader solution space and better handling complex, non-linear relationships within the data. The proposed framework is evaluated using three publicly available benchmark datasets, each corresponding to a distinct medical imaging task. The results demonstrate that the proposed framework significantly outperforms current state-of-the-art methods, achieving top accuracy rates: 98.01% on the MRI brain tumor (Kaggle) dataset, 92.81% on the Figshare MRI dataset, and 96.20% on the GastroNet dataset. This enhanced performance is further evidenced by the improved results, surpassing existing benchmarks of 97.24% (Kaggle), 91.43% (Figshare), and 95.00% (GastroNet).
Diabetes remains a significant health challenge globally, contributing to severe complications like kidney disease, vision loss, and heart issues. The application of machine learning (ML) in healthcare enables efficient and accurate disease prediction, offering avenues for early intervention and patient support. Our study introduces an innovative diabetes prediction framework, leveraging both traditional ML techniques such as Logistic Regression, SVM, Na\"ive Bayes, and Random Forest and advanced ensemble methods like AdaBoost, Gradient Boosting, Extra Trees, and XGBoost. Central to our approach is the development of a novel model, DNet, a hybrid architecture combining Convolutional Neural Network (CNN) and Long Short-Term Memory (LSTM) layers for effective feature extraction and sequential learning. The DNet model comprises an initial convolutional block for capturing essential features, followed by a residual block with skip connections to facilitate efficient information flow. Batch Normalization and Dropout are employed for robust regularization, and an LSTM layer captures temporal dependencies within the data. Using a Kaggle-sourced real-world diabetes dataset, our model evaluation spans cross-validation accuracy, precision, recall, F1 score, and ROC-AUC. Among the models, DNet demonstrates the highest efficacy with an accuracy of 99.79% and an AUC-ROC of 99.98%, establishing its potential for superior diabetes prediction. This robust hybrid architecture showcases the value of combining CNN and LSTM layers, emphasizing its applicability in medical diagnostics and disease prediction tasks.
The scarcity of high-quality multimodal biomedical data limits the ability to effectively fine-tune pretrained Large Language Models (LLMs) for specialized biomedical tasks. To address this challenge, we introduce MINT (Multimodal Integrated kNowledge Transfer), a framework that aligns unimodal large decoder models with domain-specific decision patterns from multimodal biomedical data through preference optimization. While MINT supports different optimization techniques, we primarily implement it with the Odds Ratio Preference Optimization (ORPO) framework as its backbone. This strategy enables the aligned LLMs to perform predictive tasks using text-only or image-only inputs while retaining knowledge learnt from multimodal data. MINT leverages an upstream multimodal machine learning (MML) model trained on high-quality multimodal data to transfer domain-specific insights to downstream text-only or image-only LLMs. We demonstrate its effectiveness through two key applications: (1) Rare genetic disease prediction from texts, where MINT uses a multimodal encoder model, trained on facial photos and clinical notes, to generate a preference dataset for aligning a lightweight Llama 3.2-3B-Instruct. Despite relying on text input only, the MINT-derived model outperforms models trained with SFT, RAG, or DPO, and even outperforms Llama 3.1-405B-Instruct. (2) Tissue type classification using cell nucleus images, where MINT uses a vision-language foundation model as the preference generator, containing knowledge learnt from both text and histopathological images to align downstream image-only models. The resulting MINT-derived model significantly improves the performance of Llama 3.2-Vision-11B-Instruct on tissue type classification. In summary, MINT provides an effective strategy to align unimodal LLMs with high-quality multimodal expertise through preference optimization.
With the rapid digitalization of healthcare systems, there has been a substantial increase in the generation and sharing of private health data. Safeguarding patient information is essential for maintaining consumer trust and ensuring compliance with legal data protection regulations. Machine learning is critical in healthcare, supporting personalized treatment, early disease detection, predictive analytics, image interpretation, drug discovery, efficient operations, and patient monitoring. It enhances decision-making, accelerates research, reduces errors, and improves patient outcomes. In this paper, we utilize machine learning methodologies, including differential privacy and federated learning, to develop privacy-preserving models that enable healthcare stakeholders to extract insights without compromising individual privacy. Differential privacy introduces noise to data to guarantee statistical privacy, while federated learning enables collaborative model training across decentralized datasets. We explore applying these technologies to Heart Disease Data, demonstrating how they preserve privacy while delivering valuable insights and comprehensive analysis. Our results show that using a federated learning model with differential privacy achieved a test accuracy of 85%, ensuring patient data remained secure and private throughout the process.
This research paper investigates the application of Large Language Models (LLMs) in healthcare, specifically focusing on enhancing medical decision support through Retrieval-Augmented Generation (RAG) integrated with hospital-specific data and fine-tuning using Quantized Low-Rank Adaptation (QLoRA). The system utilizes Llama 3.2-3B-Instruct as its foundation model. By embedding and retrieving context-relevant healthcare information, the system significantly improves response accuracy. QLoRA facilitates notable parameter efficiency and memory optimization, preserving the integrity of medical information through specialized quantization techniques. Our research also shows that our model performs relatively well on various medical benchmarks, indicating that it can be used to make basic medical suggestions. This paper details the system's technical components, including its architecture, quantization methods, and key healthcare applications such as enhanced disease prediction from patient symptoms and medical history, treatment suggestions, and efficient summarization of complex medical reports. We touch on the ethical considerations-patient privacy, data security, and the need for rigorous clinical validation-as well as the practical challenges of integrating such systems into real-world healthcare workflows. Furthermore, the lightweight quantized weights ensure scalability and ease of deployment even in low-resource hospital environments. Finally, the paper concludes with an analysis of the broader impact of LLMs on healthcare and outlines future directions for LLMs in medical settings.
Large language models (LLMs) offer a promising pre-screening tool, improving early disease detection and providing enhanced healthcare access for underprivileged communities. The early diagnosis of various diseases continues to be a significant challenge in healthcare, primarily due to the nonspecific nature of early symptoms, the shortage of expert medical practitioners, and the need for prolonged clinical evaluations, all of which can delay treatment and adversely affect patient outcomes. With impressive accuracy in prediction across a range of diseases, LLMs have the potential to revolutionize clinical pre-screening and decision-making for various medical conditions. In this work, we study the diagnostic capability of LLMs for Rheumatoid Arthritis (RA) with real world patients data. Patient data was collected alongside diagnoses from medical experts, and the performance of LLMs was evaluated in comparison to expert diagnoses for RA disease prediction. We notice an interesting pattern in disease diagnosis and find an unexpected \textit{misalignment between prediction and explanation}. We conduct a series of multi-round analyses using different LLM agents. The best-performing model accurately predicts rheumatoid arthritis (RA) diseases approximately 95\% of the time. However, when medical experts evaluated the reasoning generated by the model, they found that nearly 68\% of the reasoning was incorrect. This study highlights a clear misalignment between LLMs high prediction accuracy and its flawed reasoning, raising important questions about relying on LLM explanations in clinical settings. \textbf{LLMs provide incorrect reasoning to arrive at the correct answer for RA disease diagnosis.}
With the advance of high-throughput genotyping and sequencing technologies, it becomes feasible to comprehensive evaluate the role of massive genetic predictors in disease prediction. There exists, therefore, a critical need for developing appropriate statistical measurements to access the combined effects of these genetic variants in disease prediction. Predictiveness curve is commonly used as a graphical tool to measure the predictive ability of a risk prediction model on a single continuous biomarker. Yet, for most complex diseases, risk prediciton models are formed on multiple genetic variants. We therefore propose a multi-marker predictiveness curve and provide a non-parametric method to construct the curve for case-control studies. We further introduce a global predictiveness U and a partial predictiveness U to summarize prediction curve across the whole population and sub-population of clinical interest, respectively. We also demonstrate the connections of predictiveness curve with ROC curve and Lorenz curve. Through simulation, we compared the performance of the predictiveness U to other three summary indices: R square, Total Gain, and Average Entropy, and showed that Predictiveness U outperformed the other three indexes in terms of unbiasedness and robustness. Moreover, we simulated a series of rare-variants disease model, found partial predictiveness U performed better than global predictiveness U. Finally, we conducted a real data analysis, using predictiveness curve and predictiveness U to evaluate a risk prediction model for Nicotine Dependence.
Our research is motivated by the urgent global issue of a large population affected by retinal diseases, which are evenly distributed but underserved by specialized medical expertise, particularly in non-urban areas. Our primary objective is to bridge this healthcare gap by developing a comprehensive diagnostic system capable of accurately predicting retinal diseases solely from fundus images. However, we faced significant challenges due to limited, diverse datasets and imbalanced class distributions. To overcome these issues, we have devised innovative strategies. Our research introduces novel approaches, utilizing hybrid models combining deeper Convolutional Neural Networks (CNNs), Transformer encoders, and ensemble architectures sequentially and in parallel to classify retinal fundus images into 20 disease labels. Our overarching goal is to assess these advanced models' potential in practical applications, with a strong focus on enhancing retinal disease diagnosis accuracy across a broader spectrum of conditions. Importantly, our efforts have surpassed baseline model results, with the C-Tran ensemble model emerging as the leader, achieving a remarkable model score of 0.9166, surpassing the baseline score of 0.9. Additionally, experiments with the IEViT model showcased equally promising outcomes with improved computational efficiency. We've also demonstrated the effectiveness of dynamic patch extraction and the integration of domain knowledge in computer vision tasks. In summary, our research strives to contribute significantly to retinal disease diagnosis, addressing the critical need for accessible healthcare solutions in underserved regions while aiming for comprehensive and accurate disease prediction.
Heart disease remains one of the leading causes of morbidity and mortality worldwide, necessitating the development of effective diagnostic tools to enable early diagnosis and clinical decision-making. This study evaluates the impact of feature selection techniques Mutual Information (MI), Analysis of Variance (ANOVA), and Chi-Square on the predictive performance of various machine learning (ML) and deep learning (DL) models using a dataset of clinical indicators for heart disease. Eleven ML/DL models were assessed using metrics such as precision, recall, AUC score, F1-score, and accuracy. Results indicate that MI outperformed other methods, particularly for advanced models like neural networks, achieving the highest accuracy of 82.3% and recall score of 0.94. Logistic regression (accuracy 82.1%) and random forest (accuracy 80.99%) also demonstrated improved performance with MI. Simpler models such as Naive Bayes and decision trees achieved comparable results with ANOVA and Chi-Square, yielding accuracies of 76.45% and 75.99%, respectively, making them computationally efficient alternatives. Conversely, k Nearest Neighbors (KNN) and Support Vector Machines (SVM) exhibited lower performance, with accuracies ranging between 51.52% and 54.43%, regardless of the feature selection method. This study provides a comprehensive comparison of feature selection methods for heart disease prediction, demonstrating the critical role of feature selection in optimizing model performance. The results offer practical guidance for selecting appropriate feature selection techniques based on the chosen classification algorithm, contributing to the development of more accurate and efficient diagnostic tools for enhanced clinical decision-making in cardiology.
The early detection and prediction of cardiovascular diseases are crucial for reducing the severe morbidity and mortality associated with these conditions worldwide. A multi-headed self-attention mechanism, widely used in natural language processing (NLP), is operated by Transformers to understand feature interactions in feature spaces. However, the relationships between various features within biological systems remain ambiguous in these spaces, highlighting the necessity of early detection and prediction of cardiovascular diseases to reduce the severe morbidity and mortality with these conditions worldwide. We handle this issue with CardioTabNet, which exploits the strength of tab transformer to extract feature space which carries strong understanding of clinical cardiovascular data and its feature ranking. As a result, performance of downstream classical models significantly showed outstanding result. Our study utilizes the open-source dataset for heart disease prediction with 1190 instances and 11 features. In total, 11 features are divided into numerical (age, resting blood pressure, cholesterol, maximum heart rate, old peak, weight, and fasting blood sugar) and categorical (resting ECG, exercise angina, and ST slope). Tab transformer was used to extract important features and ranked them using random forest (RF) feature ranking algorithm. Ten machine-learning models were used to predict heart disease using selected features. After extracting high-quality features, the top downstream model (a hyper-tuned ExtraTree classifier) achieved an average accuracy rate of 94.1% and an average Area Under Curve (AUC) of 95.0%. Furthermore, a nomogram analysis was conducted to evaluate the model's effectiveness in cardiovascular risk assessment. A benchmarking study was conducted using state-of-the-art models to evaluate our transformer-driven framework.
Alzheimer's disease (AD) affects 50 million people worldwide and is projected to overwhelm 152 million by 2050. AD is characterized by cognitive decline due partly to disruptions in metabolic brain connectivity. Thus, early and accurate detection of metabolic brain network impairments is crucial for AD management. Chief to identifying such impairments is FDG-PET data. Despite advancements, most graph-based studies using FDG-PET data rely on group-level analysis or thresholding. Yet, group-level analysis can veil individual differences and thresholding may overlook weaker but biologically critical brain connections. Additionally, machine learning-based AD prediction largely focuses on univariate outcomes, such as disease status. Here, we introduce explainable graph-theoretical machine learning (XGML), a framework employing kernel density estimation and dynamic time warping to construct individual metabolic brain graphs that capture the distance between pair-wise brain regions and identify subgraphs most predictive of multivariate AD-related outcomes. Using FDG-PET data from the Alzheimer's Disease Neuroimaging Initiative, XGML builds metabolic brain graphs and uncovers subgraphs predictive of eight AD-related cognitive scores in new subjects. XGML shows robust performance, particularly for predicting scores measuring learning, memory, language, praxis, and orientation, such as CDRSB ($r = 0.74$), ADAS11 ($r = 0.73$), and ADAS13 ($r = 0.71$). Moreover, XGML unveils key edges jointly but differentially predictive of several AD-related outcomes; they may serve as potential network biomarkers for assessing overall cognitive decline. Together, we show the promise of graph-theoretical machine learning in biomarker discovery and disease prediction and its potential to improve our understanding of network neural mechanisms underlying AD.
Repositioning drug-disease relationships has always been a hot field of research. However, actual cases of biologically validated drug relocation remain very limited, and existing models have not yet fully utilized the structural information of the drug. Furthermore, most repositioning models are only used to complete the relationship matrix, and their practicality is poor when dealing with drug cold start problems. This paper proposes a structure-enhanced multimodal relationship prediction model (SMRP). SMPR is based on the SMILE structure of the drug, using the Mol2VEC method to generate drug embedded representations, and learn disease embedded representations through heterogeneous network graph neural networks. Ultimately, a drug-disease relationship matrix is constructed. In addition, to reduce the difficulty of users' use, SMPR also provides a cold start interface based on structural similarity based on reposition results to simply and quickly predict drug-related diseases. The repositioning ability and cold start capability of the model are verified from multiple perspectives. While the AUC and ACUPR scores of repositioning reach 99% and 61% respectively, the AUC of cold start achieve 80%. In particular, the cold start Recall indicator can reach more than 70%, which means that SMPR is more sensitive to positive samples. Finally, case analysis is used to verify the practical value of the model and visual analysis directly demonstrates the improvement of the structure to the model. For quick use, we also provide local deployment of the model and package it into an executable program.
Alzheimer's disease, a neurodegenerative disorder, is associated with neural, genetic, and proteomic factors while affecting multiple cognitive and behavioral faculties. Traditional AD prediction largely focuses on univariate disease outcomes, such as disease stages and severity. Multimodal data encode broader disease information than a single modality and may, therefore, improve disease prediction; but they often contain missing values. Recent "deeper" machine learning approaches show promise in improving prediction accuracy, yet the biological relevance of these models needs to be further charted. Integrating missing data analysis, predictive modeling, multimodal data analysis, and explainable AI, we propose OPTIMUS, a predictive, modular, and explainable machine learning framework, to unveil the many-to-many predictive pathways between multimodal input data and multivariate disease outcomes amidst missing values. OPTIMUS first applies modality-specific imputation to uncover data from each modality while optimizing overall prediction accuracy. It then maps multimodal biomarkers to multivariate outcomes using machine-learning and extracts biomarkers respectively predictive of each outcome. Finally, OPTIMUS incorporates XAI to explain the identified multimodal biomarkers. Using data from 346 cognitively normal subjects, 608 persons with mild cognitive impairment, and 251 AD patients, OPTIMUS identifies neural and transcriptomic signatures that jointly but differentially predict multivariate outcomes related to executive function, language, memory, and visuospatial function. Our work demonstrates the potential of building a predictive and biologically explainable machine-learning framework to uncover multimodal biomarkers that capture disease profiles across varying cognitive landscapes. The results improve our understanding of the complex many-to-many pathways in AD.