Principal component analysis (PCA) is a tool to capture factors that explain variation in data. Across domains, data are now collected across multiple contexts (for example, individuals with different diseases, cells of different types, or words across texts). While the factors explaining variation in data are undoubtedly shared across subsets of contexts, no tools currently exist to systematically recover such factors. We develop multi-context principal component analysis (MCPCA), a theoretical and algorithmic framework that decomposes data into factors shared across subsets of contexts. Applied to gene expression, MCPCA reveals axes of variation shared across subsets of cancer types and an axis whose variability in tumor cells, but not mean, is associated with lung cancer progression. Applied to contextualized word embeddings from language models, MCPCA maps stages of a debate on human nature, revealing a discussion between science and fiction over decades. These axes are not found by combining data across contexts or by restricting to individual contexts. MCPCA is a principled generalization of PCA to address the challenge of understanding factors underlying data across contexts.

Feature selection (FS) is essential for biomarker discovery and in the analysis of biomedical datasets. However, challenges such as high-dimensional feature space, low sample size, multicollinearity, and missing values make FS non-trivial. Moreover, FS performances vary across datasets and predictive tasks. We propose roofs, a Python package available at https://gitlab.inria.fr/compo/roofs, designed to help researchers in the choice of FS method adapted to their problem. Roofs benchmarks multiple FS methods on the user's data and generates reports that summarize a comprehensive set of evaluation metrics, including downstream predictive performance estimated using optimism correction, stability, reliability of individual features, and true positive and false positive rates assessed on semi-synthetic data with a simulated outcome. We demonstrate the utility of roofs on data from the PIONeeR clinical trial, aimed at identifying predictors of resistance to anti-PD-(L)1 immunotherapy in lung cancer. The PIONeeR dataset contained 374 multi-source blood and tumor biomarkers from 435 patients. A reduced subset of 214 features was obtained through iterative variance inflation factor pre-filtering. Of the 34 FS methods gathered in roofs, we evaluated 23 in combination with 11 classifiers (253 models in total) and identified a filter based on the union of Benjamini-Hochberg false discovery rate-adjusted p-values from t-test and logistic regression as the optimal approach, outperforming other methods including the widely used LASSO. We conclude that comprehensive benchmarking with roofs has the potential to improve the robustness and reproducibility of FS discoveries and increase the translational value of clinical models.

Early detection of cancer plays a key role in improving survival rates, but identifying reliable biomarkers from RNA-seq data is still a major challenge. The data are high-dimensional, and conventional statistical methods often fail to capture the complex relationships between genes. In this study, we introduce RGE-GCN (Recursive Gene Elimination with Graph Convolutional Networks), a framework that combines feature selection and classification in a single pipeline. Our approach builds a graph from gene expression profiles, uses a Graph Convolutional Network to classify cancer versus normal samples, and applies Integrated Gradients to highlight the most informative genes. By recursively removing less relevant genes, the model converges to a compact set of biomarkers that are both interpretable and predictive. We evaluated RGE-GCN on synthetic data as well as real-world RNA-seq cohorts of lung, kidney, and cervical cancers. Across all datasets, the method consistently achieved higher accuracy and F1-scores than standard tools such as DESeq2, edgeR, and limma-voom. Importantly, the selected genes aligned with well-known cancer pathways including PI3K-AKT, MAPK, SUMOylation, and immune regulation. These results suggest that RGE-GCN shows promise as a generalizable approach for RNA-seq based early cancer detection and biomarker discovery (https://rce-gcn.streamlit.app/ ).

Understanding the spatial architecture of the tumor microenvironment (TME) is critical to advance precision oncology. We present ProteinPNet, a novel framework based on prototypical part networks that discovers TME motifs from spatial proteomics data. Unlike traditional post-hoc explanability models, ProteinPNet directly learns discriminative, interpretable, faithful spatial prototypes through supervised training. We validate our approach on synthetic datasets with ground truth motifs, and further test it on a real-world lung cancer spatial proteomics dataset. ProteinPNet consistently identifies biologically meaningful prototypes aligned with different tumor subtypes. Through graphical and morphological analyses, we show that these prototypes capture interpretable features pointing to differences in immune infiltration and tissue modularity. Our results highlight the potential of prototype-based learning to reveal interpretable spatial biomarkers within the TME, with implications for mechanistic discovery in spatial omics.

Lung cancer risk estimation is gaining increasing importance as more countries introduce population-wide screening programs using low-dose CT (LDCT). As imaging volumes grow, scalable methods that can process entire lung volumes efficiently are essential to tap into the full potential of these large screening datasets. Existing approaches either over-rely on pixel-level annotations, limiting scalability, or analyze the lung in fragments, weakening performance. We present LungEvaty, a fully transformer-based framework for predicting 1-6 year lung cancer risk from a single LDCT scan. The model operates on whole-lung inputs, learning directly from large-scale screening data to capture comprehensive anatomical and pathological cues relevant for malignancy risk. Using only imaging data and no region supervision, LungEvaty matches state-of-the-art performance, refinable by an optional Anatomically Informed Attention Guidance (AIAG) loss that encourages anatomically focused attention. In total, LungEvaty was trained on more than 90,000 CT scans, including over 28,000 for fine-tuning and 6,000 for evaluation. The framework offers a simple, data-efficient, and fully open-source solution that provides an extensible foundation for future research in longitudinal and multimodal lung cancer risk prediction.

Accurate lung cancer tumor staging is crucial for prognosis and treatment planning. However, it remains challenging for end-to-end deep learning approaches, as such approaches often overlook spatial and anatomical information that are central to the tumor-node-metastasis system. The tumor stage depends on multiple quantitative criteria, including the tumor size and its proximity to the nearest anatomical structures, and small variations can alter the staging outcome. We propose a medically grounded hybrid pipeline that performs staging by explicitly measuring the tumor's size and distance properties rather than treating it as a pure image classification task. Our method employs specialized encoder-decoder networks to precisely segment the lung and adjacent anatomy, including the lobes, tumor, mediastinum, and diaphragm. Subsequently, we extract the necessary tumor properties, i.e. measure the largest tumor dimension and calculate the distance between the tumor and neighboring anatomical structures by a quantitative analysis of the segmentation masks. Finally, we apply rule-based tumor staging aligned with the medical guidelines. This novel framework has been evaluated on the Lung-PET-CT-Dx dataset, demonstrating superior performance compared to traditional deep learning models, achieving an overall classification accuracy of 91.36%. We report the per-stage F1-scores of 0.93 (T1), 0.89 (T2), 0.96 (T3), and 0.90 (T4), a critical evaluation aspect often omitted in prior literature. To our knowledge, this is the first study that embeds explicit clinical context into tumor stage classification. Unlike standard convolutional neural networks that operate in an uninterpretable "black box" manner, our method offers both state-of-the-art performance and transparent decision support.

Multiple instance learning (MIL) is a powerful tool to solve the weakly supervised classification in whole slide image (WSI) based pathology diagnosis. However, the current MIL methods are usually based on independent and identical distribution hypothesis, thus neglect the correlation among different instances. To address this problem, we proposed a new framework, called correlated MIL, and provided a proof for convergence. Based on this framework, we devised a Transformer based MIL (TransMIL), which explored both morphological and spatial information. The proposed TransMIL can effectively deal with unbalanced/balanced and binary/multiple classification with great visualization and in-terpretability. We conducted various experiments for three different computational pathology problems and achieved better performance and faster convergence compared with state-of-the-art methods. The test AUC for the binary tumor classification can be up to 93.09 % over CAMEL YON16 dataset. And the AUC over the cancer subtypes classification can be up to 96.03 % and 98.82 % over TCGA-NSCLC dataset and TCGA-RCC dataset, respectively.

Biomarker discovery from high-throughput transcriptomic data is crucial for advancing precision medicine. However, existing methods often neglect gene-gene regulatory relationships and lack stability across datasets, leading to conflation of spurious correlations with genuine causal effects. To address these issues, we develop a causal graph neural network (Causal-GNN) method that integrates causal inference with multi-layer graph neural networks (GNNs). The key innovation is the incorporation of causal effect estimation for identifying stable biomarkers, coupled with a GNN-based propensity scoring mechanism that leverages cross-gene regulatory networks. Experimental results demonstrate that our method achieves consistently high predictive accuracy across four distinct datasets and four independent classifiers. Moreover, it enables the identification of more stable biomarkers compared to traditional methods. Our work provides a robust, efficient, and biologically interpretable tool for biomarker discovery, demonstrating strong potential for broad application across medical disciplines.

We introduce VoxTell, a vision-language model for text-prompted volumetric medical image segmentation. It maps free-form descriptions, from single words to full clinical sentences, to 3D masks. Trained on 62K+ CT, MRI, and PET volumes spanning over 1K anatomical and pathological classes, VoxTell uses multi-stage vision-language fusion across decoder layers to align textual and visual features at multiple scales. It achieves state-of-the-art zero-shot performance across modalities on unseen datasets, excelling on familiar concepts while generalizing to related unseen classes. Extensive experiments further demonstrate strong cross-modality transfer, robustness to linguistic variations and clinical language, as well as accurate instance-specific segmentation from real-world text. Code is available at: https://www.github.com/MIC-DKFZ/VoxTell

The National Comprehensive Cancer Network (NCCN) provides evidence-based guidelines for cancer treatment. Translating complex patient presentations into guideline-compliant treatment recommendations is time-intensive, requires specialized expertise, and is prone to error. Advances in large language model (LLM) capabilities promise to reduce the time required to generate treatment recommendations and improve accuracy. We present an LLM agent-based approach to automatically generate guideline-concordant treatment trajectories for patients with non-small cell lung cancer (NSCLC). Our contributions are threefold. First, we construct a novel longitudinal dataset of 121 cases of NSCLC patients that includes clinical encounters, diagnostic results, and medical histories, each expertly annotated with the corresponding NCCN guideline trajectories by board-certified oncologists. Second, we demonstrate that existing LLMs possess domain-specific knowledge that enables high-quality proxy benchmark generation for both model development and evaluation, achieving strong correlation (Spearman coefficient r=0.88, RMSE = 0.08) with expert-annotated benchmarks. Third, we develop a hybrid approach combining expensive human annotations with model consistency information to create both the agent framework that predicts the relevant guidelines for a patient, as well as a meta-classifier that verifies prediction accuracy with calibrated confidence scores for treatment recommendations (AUROC=0.800), a critical capability for communicating the accuracy of outputs, custom-tailoring tradeoffs in performance, and supporting regulatory compliance. This work establishes a framework for clinically viable LLM-based guideline adherence systems that balance accuracy, interpretability, and regulatory requirements while reducing annotation costs, providing a scalable pathway toward automated clinical decision support.