Graph-Based Pseudo-multimodal Contrastive Learning for 12-Lead ECG Representations

12-lead electrocardiogram (ECG) is a standard, non-invasive examination widely used for diagnosing coronary artery disease, where clinical interpretation relies on comparing waveform patterns across multiple leads. However, most existing ECG analysis methods focus on single-lead signals or treat each lead independently, and typically process ECG signals as one-dimensional time-series data using CNNs or RNNs. While effective in modeling local waveform changes, such approaches have difficulty capturing inter-lead dependency and global waveform patterns essential for clinical diagnosis. To address this limitation, we propose a graph-based pseudo-multimodal contrastive learning framework called Graph-CMMC. ECG waveforms are transformed into Gramian Angular Difference Field (GADF) images to construct complementary representations of the same cardiac activity, enabling a pseudo-multimodal learning setting. Using all 12 leads, Graph-CMMC aligns waveform and GADF representations in a self-supervised manner, while a graph-based relational module is employed to model inter-lead dependency and enforce structural consistency across leads during contrastive learning. Experimental results on a multi-label coronary artery occlusion classification task demonstrate that the proposed framework achieves competitive performance compared to supervised learning methods. These results further suggest the effectiveness of using GADF as a complementary representation and incorporating explicit graph-based modeling of inter-lead dependency for learning robust 12-lead ECG representations.

Novel Knowledge-Guided Generative Methods for Synthetic Transcriptomic Data

As biomedical research increasingly relies on data-intensive tools, the quality and utility of datasets are critical. Challenges such as imbalances, biases, and ethical or legal constraints often limit access to high-quality data. Synthetic data generation can help overcome these limitations. Here, we present a comparative analysis of generative models for transcriptomic data, investigating strategies to incorporate prior biological knowledge via gene graphs. This ensures that synthetic data capture real-world gene patterns, maintaining their usefulness for downstream tasks. In particular, we introduce and benchmark three variants of the Generative Adversarial Network. Among the alternatives, MK-TGAN - an innovative multi-kernel, Graph Neural Network-based model - stands out for its performance in terms of both the realism and utility of the generated data. Unlike other methods, MK-TGAN leverages prior knowledge graphs by exploiting graph neural networks. Our results show that prior knowledge integration strategies improve performance, and that MK-TGAN consistently produces synthetic samples with superior realism and biological plausibility.

EGRL: Edge generation-guided relation-aware learning for RNA-protein interaction prediction

RNA-Protein Interactions (RPIs) are critical for regulating cellular functions. While traditional wet-lab experiments for RPI detection are costly and time-consuming, Deep Learning (DL) methods provide an efficient computational alternative for RPI Prediction (RPIP). In particular, Graph Neural Networks (GNNs) are promising, as they naturally model RPI networks. However, existing GNN-based methods often rely on homogeneous graphs or predefined meta-paths, which limit their ability to handle data sparsity and to generalize to cold-start scenarios involving unknown molecules. To address these limitations, we propose Edge Generation-guided Relation-aware Learning (EGRL), a novel framework with several key components: implicit meta-path learning to capture relational semantics without handcrafted paths; a multi-relation-aware attention mechanism for adaptive fusion of interaction patterns; a graph generator that predicts potential ("soft") edges to support cold-start nodes; and a multi-feature fusion predictor for final interaction scoring. EGRL is jointly trained with a primary task loss and an auxiliary generator loss. Comprehensive evaluations on four benchmark datasets demonstrate that EGRL achieves competitive overall performance. More importantly, it exhibits superior generalization in cold-start settings, achieving an Area Under the Receiver Operating Characteristic curve (AUROC) of 0.867 and an Area Under the Precision-Recall curve (AUPR) of 0.861 on unknown molecules, corresponding to improvements of 8.6% in AUROC and 5.0% in AUPR over prior state-of-the-art methods. The code will be released soon.

Integrating Implicit and Explicit Relational Biases through Graph-Based Multiple Instance Learning: A Case Study in Skin Lesion Diagnosis

Relational inductive biases are essential for capturing structural dependencies among data. This study investigates a dual-level relational framework for image classification, bridging the gap between implicit representation learning and explicit structural modelling. We begin by establishing a baseline using an EfficientNetB3 architecture. To move beyond standard convolutional biases, we adopt a patch-based strategy, employing a convolutional masked autoencoder to learn implicit inter-patch relationships through self-supervised reconstruction. We then extend this approach by incorporating explicit relational modelling, organizing the learned embeddings into various graph topologies, including grid-based, random, and k-nearest neighbour structures. Experimental results on the ISIC-2018 and ISIC-2019 skin lesion diagnosis benchmarks show that combining implicit inter-patch modelling with explicit graph-based message passing yields the best performance. On the ISIC-2018 test set, the baseline model achieves a balanced accuracy of 76.17%, which improves to 77.12% with implicit patch-based relational modelling. The fully integrated grid-structured Graph Attention Network further increases performance to 79.27%. Similarly, on ISIC-2019, the implicit approach reaches 59.84% balanced accuracy, while the combination of implicit and explicit modelling yields 60.67%.

CT-HEG: A Bidirectional, Timestamp-Attributed Event Graph for ICU In-Hospital Mortality Prediction - An Architectural Ablation Study

Accurate ICU mortality prediction requires modeling irregular clinical observations across heterogeneous entity types. Existing sequence models handle irregular sampling but ignore typed relational structure; existing graph models assume fixed-interval inputs. We introduce the Continuous-Time Heterogeneous EHR Graph (CT-HEG) schema and evaluate which architectural choices drive predictive performance. CT-HEG encodes each ICU stay as a typed, timestamped graph with three node types (visit, vital, lab_event) and 2D edge attributes (t_hours/48, value_norm) encoding timing and value without imputation. We instantiate CT-HEG as CHIRP-Net, a four-layer heterogeneous GATv2Conv network, evaluated on MIMIC-IV v3.1 (31,142 ICU stays, LOS>=48h, 13.4% mortality) with five seeds and bootstrapped confidence intervals, against logistic regression, mTAND, a Transformer, and GRU-D, plus an ablation study. CHIRP-Net achieved 5-seed mean AUROC 0.8449+/-0.0071 (AUPRC 0.4958+/-0.0209); the ensemble achieved AUROC 0.8618 (95% CI: 0.8485-0.8745). Removing reverse edges disconnected observation nodes from the visit readout, cutting AUROC by 0.1968+/-0.0073. Time-attentive edge features contributed 0.0247+/-0.0093 AUROC. Collapsing heterogeneous edge types into one relation (7x fewer parameters) outperformed the full model on all seeds. Post-calibration ECE was 0.0307. Temporal and demographic subgroup analyses were explored but not reported here, pending follow-up work. Bidirectional connectivity was necessary for the model to use its inputs at all, and CT-HEG was reasonably well calibrated after validation-fitted temperature scaling. These results support CT-HEG for irregular EHR data, while external validation, a pre-specified temporal evaluation, and a demographic fairness audit remain necessary before any claim of robustness. Code: https://github.com/nasiruddinstudents-ctrl/chirp-net-mimic-iv.

MPP-GNN: Subject-Adaptive Community Detection for fMRI-Based Alzheimer's Disease Classification

Functional magnetic resonance imaging (fMRI) is a widely used technique for studying the brain. Recent methods that utilize graph neural networks (GNNs) for analysis of brain functional connectivity have shown great potential for the classification of brain disorders, such as Alzheimer's disease (AD). However, these methods often assume a preset number of functional modules across all subjects, which overlooks inter-subject variability. In addition, the discovered modules are rarely used to directly guide the learned connectivity patterns. Here, to address these issues, we propose a Meta Probabilistic Pooling GNN (MPP-GNN). We frame the model's task as a coupled, bilevel optimization that performs adaptive graph partitioning hierarchically to discover subject-specific modules and then uses the discovered brain modules as an explicit prior to guide edge refinement and representation learning. We validate MPP-GNN on two public datasets for AD classification, achieving the highest AUC in comparison to established baselines for both datasets. Furthermore, our analysis demonstrates that MPP-GNN shows significant alignment with the canonical functional-network organization defined by the Yeo brain atlas and reveals a network-level dedifferentiation pattern for AD.

HierarchicalDAEW: Domain-Aware Edge-Weighted Graph Convolution with Evidential Uncertainty for Multi-Section Spatial Gene Expression Prediction from H&E Histology

Spatial transcriptomics assays remain costly and technically demanding, restricting transcriptome-wide profiling to specialist settings and preventing routine clinical deployment. Predicting spatially resolved gene expression from H&E histology could close this gap, yet current methods largely ignore the underlying tissue architecture and rarely quantify how their predictions can be trusted. We introduce HierarchicalDAEW, a dual-graph architecture that addresses both gaps. On the spot graph, a Domain-Aware Edge-Weighted convolutional operator learns separate projections for inter-domain, intra-domain, and boundary edges derived from Leiden clustering, allowing the model to treat tissue heterogeneity as an explicit structural signal rather than an implicit one. A second gene-level graph then fuses protein-protein interaction priors from STRING-DB with tissue-specific co-expression through learned attention gating, propagating predictions from a landmark gene set to a broader gene panel. Reliability is handled through evidential uncertainty estimation, which produces far better calibrated confidence intervals than Monte Carlo dropout under identical conditions. Across six human Visium sections spanning breast, colorectal, prostate, and cerebellar tissue, and against thirteen published baselines, HierarchicalDAEW achieves the strongest correlation with ground-truth expression, with gains that hold up under multi-seed reproducibility checks and negative controls that rule out positional shortcuts. Ablations further confirm that both the domain-aware edge typing and the hierarchical depth are necessary to this improvement, and calibrated uncertainty estimates identify low-confidence predictions for pathologist review before clinical action.

Higher-Order Cell Tracking Transformer

Reconstructing lineages from live-imaging microscopy requires linking cell detections across time, including through cell divisions. A common approach is to construct a candidate graph and associate cell segmentations (nodes) across frames. However, these and other existing methods overlook two structural obstacles in candidate tracking graphs: (i) cell divisions entangle distinct lineage paths in the node embedding space, and (ii) edges sharing a node have near-random label agreement, so the candidate-graph topology carries no useful information for graph neural networks to aggregate. We propose the \textbf{Higher-Order Cell Tracking Transformer} (HOCT), an edge-centric architecture in which candidate cell links attend to one another under a 3D geometric prior, resolving both issues. Evaluated on the Cell Tracking Challenge and a bacteria division benchmark, HOCT achieves state-of-the-art results without deep pre-trained image encoders. Moreover, the proposed approach is easier to fine-tune, quickly reducing tracking errors by 59% with 400 annotations in a human-in-the-loop setting, outperforming LoRA fine-tuning of competing transformer baselines (6.75% improvement).

Asymmetric Focal Loss Improves Graph Neural Network Prediction of Drug-Drug Interactions

Background: Graph neural networks improve computational prediction of polypharmacy side effects, but standard binary cross-entropy training allocates equal capacity to well-classified and difficult examples, potentially missing clinically significant interactions. We evaluated whether an asymmetric focal objective could improve multi-relational drug-drug interaction (DDI) prediction by emphasizing difficult positive interactions. Methods: ClinicalFocal loss was integrated into a relation-aware graph convolutional network using molecular fingerprints, physicochemical descriptors, and learned embeddings. The model was evaluated on TWOSIDES using five-fold cross-validation with identical experimental conditions (architecture, features, data partitions, hyperparameters, and random seeds) for ClinicalFocal loss and binary cross-entropy baseline. Results: ClinicalFocal loss increased accuracy from 0.699 to 0.892 (+19.3 percentage points) and F1 score from 0.700 to 0.894 (+19.4 percentage points). AUROC increased from 0.766 to 0.914, and AUCPR increased from 0.714 to 0.860. The false-negative rate decreased from 29.8% to 9.1%, while specificity increased from 69.6% to 87.5%. Overall classification error decreased from 30.1% to 10.8%, corresponding to a 64.1% relative reduction. Improvements were consistent across all five folds. Conclusions: Asymmetric focal optimization improved classification and ranking performance while achieving 90.9% recall for observed interaction triples, without modifying the underlying architecture. Loss-function design is a direct, tunable lever for improving graph-based DDI prediction.

Navigating Hierarchy: Hyperbolic Learning on Brain Graphs for Disorder Diagnosis

Functional brain networks exhibit a hierarchical organization across ROI, community, and whole-brain levels, supporting local processing, inter-community coordination, and global integration. Recent studies have demonstrated that brain community-aware modeling is beneficial for both diagnosis and biomarker identification of brain networks. However, existing brain graph modeling methods often struggle to model ROI-community interactions, thereby failing to fully exploit the hierarchy across ROI, community, and whole-brain network levels. To address this issue, inspired by deep hyperbolic learning in modeling hierarchical structures, we propose a novel framework, termed Hyperbolic Learning on Brain Graphs (HLBG), for brain network analysis. The core idea of HLBG is to exploit the inherent hierarchical geometry of hyperbolic space to model the hierarchical relationships among ROIs, functional communities, and the whole-brain network, thereby learning hierarchy-aware and highly discriminative representations for brain network data. Specifically, HLBG first projects representations from ROIs, communities, and the whole-brain network into Lorentzian hyperbolic space. Then, the multi-level hierarchy is imposed via two geometric entailment constraints. In addition, we introduce a new Graph-aware Mamba (GaMamba) model, which incorporates topology-derived structural prompts into Mamba to capture long-range dependencies while preserving graph topological information. Experiments on ABIDE-I and REST-MDD demonstrate that HLBG outperforms state-of-the-art methods and identifies disorder-relevant functional biomarkers.

Longitudinal and Graph-Augmented Prediction of Adolescent Substance Use Onset in the ABCD Study

Early identification of adolescent substance-use risk is an important prevention challenge, yet the relative value of baseline characteristics, longitudinal trajectories, and relational context remains unclear. Using data from approximately 11,860 participants in the Adolescent Brain Cognitive Development (ABCD) Study, we compare cross-sectional, longitudinal, and graph-based approaches for predicting alcohol sipping, alcohol use, marijuana use, and alcohol/marijuana use. We evaluate tree-based models, recurrent neural networks, and Temporal Graph Convolutional Networks (T-GCNs) constructed from family, school, and feature-similarity graphs. Longitudinal models consistently outperform baseline models, with temporal XGBoost achieving the strongest standalone performance. Although T-GCNs generally do not surpass temporal XGBoost, graph-derived risk scores provide complementary information. Combining temporal XGBoost and T-GCN predictions through score-level stacking yields the best performance across all outcomes, achieving AUC-ROC values above 0.79. Feature analyses identify peer deviance, age, externalizing symptoms, parental monitoring, cultural norms, and neighborhood context as important predictors of substance use onset. These findings demonstrate the value of longitudinal modeling for substance-use prediction and suggest that graph-based representations can provide effective auxiliary risk signals.

Artemis: Anatomy-Resolved inTervention for Eliminating Multimodal NeuroImage confounderS

Multimodal neuroimaging, integrating functional connectivity from fMRI and structural connectivity from DTI, enables non-invasive analysis of brain networks using graph neural networks. However, demographic factors such as age and sex systematically confound the relationship between brain connectivity and clinical outcomes, causing GNNs to exploit spurious shortcuts rather than learning causally invariant representations. While recent causal GNN methods introduce causality at the graph-modeling level, their causal mechanisms remain domain-agnostic without accounting for the real-world confounders inherent in clinical neuroimaging data. Moreover, brain networks are constructed from atlas-based parcellations where each region exhibits distinct sensitivity to demographic factors, necessitating region-aware adjustment. We propose Artemis, a region-level causal framework that bridges this gap with causal intervention at each brain region independently by learning region-specific confounder representations with lightweight parameters. Our adjustment comprehensively utilized the multimodal functional and structural features for graph reasoning as a plug-in module compatible with arbitrary GNN backbones. Experiments on three benchmarks, ADNI for disease diagnosis, OASIS for dementia staging, and HCP for sex classification, demonstrate consistent improvements over representative GNN-based baselines. Multiple supporting experiments further demonstrate statistical significance and neuroscientific interpretability.

Querying Counterfactuals on Tissue Graphs with Supervised Disentanglement

Tissue graph counterfactuals ask how a cell's expression would change under altered spatial neighbor contexts. Such queries are central to predicting cell behavior in tissues, but lack a unified definition, with existing methods targeting specific intervention types or treating cells as i.i.d. In this work, we first formalize tissue graph counterfactuals as a class of spatial interventions that either rewire connections between cells (edge perturbation) or modify the expression of their neighbors (node perturbation). We then introduce Cellina (https://cellina.readthedocs.io) - a framework that uses supervised disentanglement to decompose a cell's intrinsic state from its spatial context, using the latter as a conditioning input for counterfactual predictions. Across benchmarks spanning over 2.5 million spatially-resolved cells in colorectal cancer and mouse brain, Cellina outperforms spatially-informed and non-spatial competitors in in-silico graph perturbations, disentanglement, and scalability. Additionally, we show that Cellina reveals biologically distinct cancer subdomains in an unsupervised manner and enables targeted neighbor perturbation simulations.

BRIDGE: Biological Evidence Refinement and Heterogeneous Dynamic Gating for Gene Regulatory Networks

Motivation: Gene regulatory network inference from single-cell RNA sequencing (scRNA-seq) data is important for uncovering cell-state-specific transcriptional programs. However, scRNA-seq measurements are sparse and noisy, and experimentally validated TF-target interactions remain limited, making reliable inference challenging. Although graph neural networks have advanced GRN prediction, existing methods often rely on biologically unconstrained graph augmentation, such as random edge perturbation, and insufficiently control information transfer between genes and cells. These limitations may distort regulatory structures and weaken robustness under noisy and weakly supervised settings. Results: To address these issues, we propose an innovative framework named Biological Evidence Refinement and Heterogeneous Dynamic Gating for Gene Regulatory Networks (BRIDGE). BRIDGE extracts gene and cell representations from the expression matrix and its matrix dual, and performs contrastive learning in the gene space and cell space between self and neighbors across the co-expression-refined regulatory view and the original graph. It then applies heterogeneous gated encoding to adaptively regulate information transfer between genes and cells, enabling robust transcription factor-to-target gene prediction. Experiments on benchmark datasets spanning three network types and seven cell types show that BRIDGE achieves state-of-the-art AUROC and AUPRC in most settings. In particular, on Specific networks, BRIDGE improves average AUPRC by 5% over the second-best baseline, GCLink. In cross-cell-type few-shot transfer, BRIDGE consistently outperforms GCLink and GENELink across all six target cell types. A case study on hESC further supports the biological relevance of the predictions, with 9 of the top 10 and 46 of the top 100 novel TF-target interactions validated by ChIPBase.