Integration and analysis of multi-omics data provide valuable insights for cancer subtype classification. However, such data are inherently heterogeneous, high-dimensional, and exhibit complex intra- and inter-modality dependencies. Recent advances in graph neural networks (GNNs) offer powerful tools for modeling such structure. Yet, most existing methods rely on prior knowledge or predefined similarity networks to construct graphs, which are often undirected or unweighted, failing to capture the directionality and strength of biological interactions. Interpretability at both the modality and feature levels also remains limited. To address these challenges, we propose TF-DWGNet, a novel Graph Neural Network framework that combines tree-based Directed Weighted graph construction with Tensor Fusion for multiclass cancer subtype classification. TF-DWGNet introduces two key innovations: a supervised tree-based approach for constructing directed, weighted graphs tailored to each omics modality, and a tensor fusion mechanism that captures unimodal, bimodal, and trimodal interactions using low-rank decomposition for efficiency. TF-DWGNet enables modality-specific representation learning, joint embedding fusion, and interpretable subtype prediction. Experiments on real-world cancer datasets show that TF-DWGNet consistently outperforms state-of-the-art baselines across multiple metrics and statistical tests. Moreover, it provides biologically meaningful insights by ranking influential features and modalities. These results highlight TF-DWGNet's potential for effective and interpretable multi-omics integration in cancer research.

Cancer subtype classification is crucial for personalized treatment and prognostic assessment. However, effectively integrating multi-omic data remains challenging due to the heterogeneous nature of genomic, epigenomic, and transcriptomic features. In this work, we propose Modality-Aware Cross-Attention MoXGATE, a novel deep-learning framework that leverages cross-attention and learnable modality weights to enhance feature fusion across multiple omics sources. Our approach effectively captures inter-modality dependencies, ensuring robust and interpretable integration. Through experiments on Gastrointestinal Adenocarcinoma (GIAC) and Breast Cancer (BRCA) datasets from TCGA, we demonstrate that MoXGATE outperforms existing methods, achieving 95\% classification accuracy. Ablation studies validate the effectiveness of cross-attention over simple concatenation and highlight the importance of different omics modalities. Moreover, our model generalizes well to unseen cancer types e.g., breast cancer, underscoring its adaptability. Key contributions include (1) a cross-attention-based multi-omic integration framework, (2) modality-weighted fusion for enhanced interpretability, (3) application of focal loss to mitigate data imbalance, and (4) validation across multiple cancer subtypes. Our results indicate that MoXGATE is a promising approach for multi-omic cancer subtype classification, offering improved performance and biological generalizability.

Molecular subtyping of breast cancer is crucial for personalized treatment and prognosis. Traditional classification approaches rely on either histopathological images or gene expression profiling, limiting their predictive power. In this study, we propose a deep multimodal learning framework that integrates histopathological images and gene expression data to classify breast cancer into BRCA.Luminal and BRCA.Basal / Her2 subtypes. Our approach employs a ResNet-50 model for image feature extraction and fully connected layers for gene expression processing, with a cross-attention fusion mechanism to enhance modality interaction. We conduct extensive experiments using five-fold cross-validation, demonstrating that our multimodal integration outperforms unimodal approaches in terms of classification accuracy, precision-recall AUC, and F1-score. Our findings highlight the potential of deep learning for robust and interpretable breast cancer subtype classification, paving the way for improved clinical decision-making.

Accurate classification of histological subtypes of non-small cell lung cancer (NSCLC) is essential in the era of precision medicine, yet current invasive techniques are not always feasible and may lead to clinical complications. This study presents a multi-stage intermediate fusion approach to classify NSCLC subtypes from CT and PET images. Our method integrates the two modalities at different stages of feature extraction, using voxel-wise fusion to exploit complementary information across varying abstraction levels while preserving spatial correlations. We compare our method against unimodal approaches using only CT or PET images to demonstrate the benefits of modality fusion, and further benchmark it against early and late fusion techniques to highlight the advantages of intermediate fusion during feature extraction. Additionally, we compare our model with the only existing intermediate fusion method for histological subtype classification using PET/CT images. Our results demonstrate that the proposed method outperforms all alternatives across key metrics, with an accuracy and AUC equal to 0.724 and 0.681, respectively. This non-invasive approach has the potential to significantly improve diagnostic accuracy, facilitate more informed treatment decisions, and advance personalized care in lung cancer management.

Molecular subtyping of cancer is recognized as a critical and challenging upstream task for personalized therapy. Existing deep learning methods have achieved significant performance in this domain when abundant data samples are available. However, the acquisition of densely labeled samples for cancer molecular subtypes remains a significant challenge for conventional data-intensive deep learning approaches. In this work, we focus on the few-shot molecular subtype prediction problem in heterogeneous and small cancer datasets, aiming to enhance precise diagnosis and personalized treatment. We first construct a new few-shot dataset for cancer molecular subtype classification and auxiliary cancer classification, named TCGA Few-Shot, from existing publicly available datasets. To effectively leverage the relevant knowledge from both tasks, we introduce a task-specific embedding-based meta-learning framework (TSEML). TSEML leverages the synergistic strengths of a model-agnostic meta-learning (MAML) approach and a prototypical network (ProtoNet) to capture diverse and fine-grained features. Comparative experiments conducted on the TCGA Few-Shot dataset demonstrate that our TSEML framework achieves superior performance in addressing the problem of few-shot molecular subtype classification.

Electroencephalogram (EEG)-based seizure subtype classification enhances clinical diagnosis efficiency. Source-free semi-supervised domain adaptation (SF-SSDA), which transfers a pre-trained model to a new dataset with no source data and limited labeled target data, can be used for privacy-preserving seizure subtype classification. This paper considers two challenges in SF-SSDA for EEG-based seizure subtype classification: 1) How to effectively fuse both raw EEG data and expert knowledge in classifier design? 2) How to align the source and target domain distributions for SF-SSDA? We propose a Knowledge-Data Fusion based SF-SSDA approach, KDF-MutualSHOT, for EEG-based seizure subtype classification. In source model training, KDF uses Jensen-Shannon Divergence to facilitate mutual learning between a feature-driven Decision Tree-based model and a data-driven Transformer-based model. To adapt KDF to a new target dataset, an SF-SSDA algorithm, MutualSHOT, is developed, which features a consistency-based pseudo-label selection strategy. Experiments on the public TUSZ and CHSZ datasets demonstrated that KDF-MutualSHOT outperformed other supervised and source-free domain adaptation approaches in cross-subject seizure subtype classification.

Automated disease diagnosis using medical image analysis relies on deep learning, often requiring large labeled datasets for supervised model training. Diseases like Acute Myeloid Leukemia (AML) pose challenges due to scarce and costly annotations on a single-cell level. Multiple Instance Learning (MIL) addresses weakly labeled scenarios but necessitates powerful encoders typically trained with labeled data. In this study, we explore Self-Supervised Learning (SSL) as a pre-training approach for MIL-based AML subtype classification from blood smears, removing the need for labeled data during encoder training. We investigate the three state-of-the-art SSL methods SimCLR, SwAV, and DINO, and compare their performance against supervised pre-training. Our findings show that SSL-pretrained encoders achieve comparable performance, showcasing the potential of SSL in MIL. This breakthrough offers a cost-effective and data-efficient solution, propelling the field of AI-based disease diagnosis.

The effective management of brain tumors relies on precise typing, subtyping, and grading. This study advances patient care with findings from rigorous multiple instance learning experimentations across various feature extractors and aggregators in brain tumor histopathology. It establishes new performance benchmarks in glioma subtype classification across multiple datasets, including a novel dataset focused on the Indian demographic (IPD- Brain), providing a valuable resource for existing research. Using a ResNet-50, pretrained on histopathology datasets for feature extraction, combined with the Double-Tier Feature Distillation (DTFD) feature aggregator, our approach achieves state-of-the-art AUCs of 88.08 on IPD-Brain and 95.81 on the TCGA-Brain dataset, respectively, for three-way glioma subtype classification. Moreover, it establishes new benchmarks in grading and detecting IHC molecular biomarkers (IDH1R132H, TP53, ATRX, Ki-67) through H&E stained whole slide images for the IPD-Brain dataset. The work also highlights a significant correlation between the model decision-making processes and the diagnostic reasoning of pathologists, underscoring its capability to mimic professional diagnostic procedures.

The challenge in biomarker discovery using machine learning from omics data lies in the abundance of molecular features but scarcity of samples. Most feature selection methods in machine learning require evaluating various sets of features (models) to determine the most effective combination. This process, typically conducted using a validation dataset, involves testing different feature sets to optimize the model's performance. Evaluations have performance estimation error and when the selection involves many models the best ones are almost certainly overestimated. Biomarker identification with feature selection methods can be addressed as a multi-objective problem with trade-offs between predictive ability and parsimony in the number of features. Genetic algorithms are a popular tool for multi-objective optimization but they evolve numerous solutions thus are prone to overestimation. Methods have been proposed to reduce the overestimation after a model has already been selected in single-objective problems, but no algorithm existed capable of reducing the overestimation during the optimization, improving model selection, or applied in the more general multi-objective domain. We propose DOSA-MO, a novel multi-objective optimization wrapper algorithm that learns how the original estimation, its variance, and the feature set size of the solutions predict the overestimation. DOSA-MO adjusts the expectation of the performance during the optimization, improving the composition of the solution set. We verify that DOSA-MO improves the performance of a state-of-the-art genetic algorithm on left-out or external sample sets, when predicting cancer subtypes and/or patient overall survival, using three transcriptomics datasets for kidney and breast cancer.

Multi-phase CT is widely adopted for the diagnosis of kidney cancer due to the complementary information among phases. However, the complete set of multi-phase CT is often not available in practical clinical applications. In recent years, there have been some studies to generate the missing modality image from the available data. Nevertheless, the generated images are not guaranteed to be effective for the diagnosis task. In this paper, we propose a unified framework for kidney cancer diagnosis with incomplete multi-phase CT, which simultaneously recovers missing CT images and classifies cancer subtypes using the completed set of images. The advantage of our framework is that it encourages a synthesis model to explicitly learn to generate missing CT phases that are helpful for classifying cancer subtypes. We further incorporate lesion segmentation network into our framework to exploit lesion-level features for effective cancer classification in the whole CT volumes. The proposed framework is based on fully 3D convolutional neural networks to jointly optimize both synthesis and classification of 3D CT volumes. Extensive experiments on both in-house and external datasets demonstrate the effectiveness of our framework for the diagnosis with incomplete data compared with state-of-the-art baselines. In particular, cancer subtype classification using the completed CT data by our method achieves higher performance than the classification using the given incomplete data.