Aakash Tripathi

Sabeen Ahmed, Ian E. Nielsen, Aakash Tripathi et al.

Transformer architecture has widespread applications, particularly in Natural Language Processing and computer vision. Recently Transformers have been employed in various aspects of time-series analysis. This tutorial provides an overview of the Transformer architecture, its applications, and a collection of examples from recent research papers in time-series analysis. We delve into an explanation of the core components of the Transformer, including the self-attention mechanism, positional encoding, multi-head, and encoder/decoder. Several enhancements to the initial, Transformer architecture are highlighted to tackle time-series tasks. The tutorial also provides best practices and techniques to overcome the challenge of effectively training Transformers for time-series analysis.

Asim Waqas, Aakash Tripathi, Ravi P. Ramachandran et al.

Cancer has relational information residing at varying scales, modalities, and resolutions of the acquired data, such as radiology, pathology, genomics, proteomics, and clinical records. Integrating diverse data types can improve the accuracy and reliability of cancer diagnosis and treatment. There can be disease-related information that is too subtle for humans or existing technological tools to discern visually. Traditional methods typically focus on partial or unimodal information about biological systems at individual scales and fail to encapsulate the complete spectrum of the heterogeneous nature of data. Deep neural networks have facilitated the development of sophisticated multimodal data fusion approaches that can extract and integrate relevant information from multiple sources. Recent deep learning frameworks such as Graph Neural Networks (GNNs) and Transformers have shown remarkable success in multimodal learning. This review article provides an in-depth analysis of the state-of-the-art in GNNs and Transformers for multimodal data fusion in oncology settings, highlighting notable research studies and their findings. We also discuss the foundations of multimodal learning, inherent challenges, and opportunities for integrative learning in oncology. By examining the current state and potential future developments of multimodal data integration in oncology, we aim to demonstrate the promising role that multimodal neural networks can play in cancer prevention, early detection, and treatment through informed oncology practices in personalized settings.

Aakash Tripathi, Asim Waqas, Kavya Venkatesan et al.

The advancements in data acquisition, storage, and processing techniques have resulted in the rapid growth of heterogeneous medical data. Integrating radiological scans, histopathology images, and molecular information with clinical data is essential for developing a holistic understanding of the disease and optimizing treatment. The need for integrating data from multiple sources is further pronounced in complex diseases such as cancer for enabling precision medicine and personalized treatments. This work proposes Multimodal Integration of Oncology Data System (MINDS) - a flexible, scalable, and cost-effective metadata framework for efficiently fusing disparate data from public sources such as the Cancer Research Data Commons (CRDC) into an interconnected, patient-centric framework. MINDS offers an interface for exploring relationships across data types and building cohorts for developing large-scale multimodal machine learning models. By harmonizing multimodal data, MINDS aims to potentially empower researchers with greater analytical ability to uncover diagnostic and prognostic insights and enable evidence-based personalized care. MINDS tracks granular end-to-end data provenance, ensuring reproducibility and transparency. The cloud-native architecture of MINDS can handle exponential data growth in a secure, cost-optimized manner while ensuring substantial storage optimization, replication avoidance, and dynamic access capabilities. Auto-scaling, access controls, and other mechanisms guarantee pipelines' scalability and security. MINDS overcomes the limitations of existing biomedical data silos via an interoperable metadata-driven approach that represents a pivotal step toward the future of oncology data integration.

Carlos Garcia-Fernandez, Luis Felipe, Monique Shotande et al.

Large language models (LLMs) show promise in healthcare, but hallucinations remain a major barrier to clinical use. We present CHECK, a continuous-learning framework that integrates structured clinical databases with a classifier grounded in information theory to detect both factual and reasoning-based hallucinations. Evaluated on 1500 questions from 100 pivotal clinical trials, CHECK reduced LLama3.3-70B-Instruct hallucination rates from 31% to 0.3% - making an open source model state of the art. Its classifier generalized across medical benchmarks, achieving AUCs of 0.95-0.96, including on the MedQA (USMLE) benchmark and HealthBench realistic multi-turn medical questioning. By leveraging hallucination probabilities to guide GPT-4o's refinement and judiciously escalate compute, CHECK boosted its USMLE passing rate by 5 percentage points, achieving a state-of-the-art 92.1%. By suppressing hallucinations below accepted clinical error thresholds, CHECK offers a scalable foundation for safe LLM deployment in medicine and other high-stakes domains.

Aakash Tripathi, Asim Waqas, Matthew B. Schabath et al.

HONeYBEE (Harmonized ONcologY Biomedical Embedding Encoder) is an open-source framework that integrates multimodal biomedical data for oncology applications. It processes clinical data (structured and unstructured), whole-slide images, radiology scans, and molecular profiles to generate unified patient-level embeddings using domain-specific foundation models and fusion strategies. These embeddings enable survival prediction, cancer-type classification, patient similarity retrieval, and cohort clustering. Evaluated on 11,400+ patients across 33 cancer types from The Cancer Genome Atlas (TCGA), clinical embeddings showed the strongest single-modality performance with 98.5% classification accuracy and 96.4% precision@10 in patient retrieval. They also achieved the highest survival prediction concordance indices across most cancer types. Multimodal fusion provided complementary benefits for specific cancers, improving overall survival prediction beyond clinical features alone. Comparative evaluation of four large language models revealed that general-purpose models like Qwen3 outperformed specialized medical models for clinical text representation, though task-specific fine-tuning improved performance on heterogeneous data such as pathology reports.

Asim Waqas, Aakash Tripathi, Sabeen Ahmed et al.

Multi-omics research has enhanced our understanding of cancer heterogeneity and progression. Investigating molecular data through multi-omics approaches is crucial for unraveling the complex biological mechanisms underlying cancer, thereby enabling more effective diagnosis, treatment, and prevention strategies. However, predicting patient outcomes through the integration of all available multi-omics data is still an under-study research direction. Here, we present SeNMo, a foundation model that has been trained on multi-omics data across 33 cancer types. SeNMo is particularly efficient in handling multi-omics data characterized by high-width and low-length attributes. We trained SeNMo for the task of overall survival of patients using pan-cancer multi-omics data involving 33 cancer sites from the GDC. The training multi-omics data includes gene expression, DNA methylation, miRNA expression, DNA mutations, protein expression modalities, and clinical data. SeNMo was validated on two independent cohorts: Moffitt Cancer Center and CPTAC lung squamous cell carcinoma. We evaluated the model's performance in predicting patient's overall survival using the C-Index. SeNMo performed consistently well in the training regime, reflected by the validation C-Index of 0.76 on GDC's public data. In the testing regime, SeNMo performed with a C-Index of 0.758 on a held-out test set. The model showed an average accuracy of 99.8% on the task of classifying the primary cancer type on the pan-cancer test cohort. SeNMo demonstrated robust performance on the classification task of predicting the primary cancer type of patients. SeNMo further demonstrated significant performance in predicting tertiary lymph structures from multi-omics data, showing generalizability across cancer types, molecular data types, and clinical endpoints.

Aakash Tripathi, Ian E. Nielsen, Muhammad Umer et al.

Transcription Factor Binding Site (TFBS) prediction is crucial for understanding gene regulation and various biological processes. This study introduces a novel Mixture of Experts (MoE) approach for TFBS prediction, integrating multiple pre-trained Convolutional Neural Network (CNN) models, each specializing in different TFBS patterns. We evaluate the performance of our MoE model against individual expert models on both in-distribution and out-of-distribution (OOD) datasets, using six randomly selected transcription factors (TFs) for OOD testing. Our results demonstrate that the MoE model achieves competitive or superior performance across diverse TF binding sites, particularly excelling in OOD scenarios. The Analysis of Variance (ANOVA) statistical test confirms the significance of these performance differences. Additionally, we introduce ShiftSmooth, a novel attribution mapping technique that provides more robust model interpretability by considering small shifts in input sequences. Through comprehensive explainability analysis, we show that ShiftSmooth offers superior attribution for motif discovery and localization compared to traditional Vanilla Gradient methods. Our work presents an efficient, generalizable, and interpretable solution for TFBS prediction, potentially enabling new discoveries in genome biology and advancing our understanding of transcriptional regulation.

Aakash Tripathi, Asim Waqas, Matthew B. Schabath et al.

Accurate cancer survival prediction requires integration of diverse data modalities that reflect the complex interplay between imaging, clinical parameters, and textual reports. However, existing multimodal approaches suffer from simplistic fusion strategies, massive computational requirements, and lack of interpretability-critical barriers to clinical adoption. We present EAGLE (Efficient Alignment of Generalized Latent Embeddings), a novel deep learning framework that addresses these limitations through attention-based multimodal fusion with comprehensive attribution analysis. EAGLE introduces four key innovations: (1) dynamic cross-modal attention mechanisms that learn hierarchical relationships between modalities, (2) massive dimensionality reduction (99.96%) while maintaining predictive performance, (3) three complementary attribution methods providing patient-level interpretability, and (4) a unified pipeline enabling seamless adaptation across cancer types. We evaluated EAGLE on 911 patients across three distinct malignancies: glioblastoma (GBM, n=160), intraductal papillary mucinous neoplasms (IPMN, n=171), and non-small cell lung cancer (NSCLC, n=580). Patient-level analysis showed high-risk individuals relied more heavily on adverse imaging features, while low-risk patients demonstrated balanced modality contributions. Risk stratification identified clinically meaningful groups with 4-fold (GBM) to 5-fold (NSCLC) differences in median survival, directly informing treatment intensity decisions. By combining state-of-the-art performance with clinical interpretability, EAGLE bridges the gap between advanced AI capabilities and practical healthcare deployment, offering a scalable solution for multimodal survival prediction that enhances both prognostic accuracy and physician trust in automated predictions.

Luis Felipe, Carlos Garcia, Issam El Naqa et al.

The need for robust and diverse data sets to train clinical large language models (cLLMs) is critical given that currently available public repositories often prove too limited in size or scope for comprehensive medical use. While resources like PubMed provide foundational medical literature, they capture only a narrow range of formal publications and omit the broader medical discourse on the internet. To address these deficits, we introduce TheBlueScrubs-v1, a curated dataset of over 25 billion medical tokens - nearly three times larger than PubMed - drawn from a broad-scale internet corpus. Our two-stage filtering pipeline employs a Logistic Regression model for document screening (achieving an AUC of approximately 0.95 on external validation), followed by verification via a 70B-parameter Llama 3.1 instruct model. Each text is assigned three LLM-based quality scores encompassing medical relevance, precision and factual detail, and safety and ethical standards. Clinician reviews confirm high concordance with these automated evaluations, and a specialized cancer classifier further labels approximately 11 billion oncology tokens. Two demonstration tasks highlight the dataset's practical value: first, we distill the safety evaluations to a smaller BERT-style model that reaches an AUC near 0.96 on unseen data; second, we fine-tune a compact LLM on a filtered subset, showing measurable improvements over standard baselines in medical benchmarks as well as private ones. This Data Descriptor details the dataset's creation and validation, underscoring its potential utility for medical AI research.

Asim Waqas, Aakash Tripathi, Paul Stewart et al.

Cancer clinics capture disease data at various scales, from genetic to organ level. Current bioinformatic methods struggle to handle the heterogeneous nature of this data, especially with missing modalities. We propose PARADIGM, a Graph Neural Network (GNN) framework that learns from multimodal, heterogeneous datasets to improve clinical outcome prediction. PARADIGM generates embeddings from multi-resolution data using foundation models, aggregates them into patient-level representations, fuses them into a unified graph, and enhances performance for tasks like survival analysis. We train GNNs on pan-Squamous Cell Carcinomas and validate our approach on Moffitt Cancer Center lung SCC data. Multimodal GNN outperforms other models in patient survival prediction. Converging individual data modalities across varying scales provides a more insightful disease view. Our solution aims to understand the patient's circumstances comprehensively, offering insights on heterogeneous data integration and the benefits of converging maximum data views.