Dominik Heider

Tiago da Silva, Bruna Bazaluk, Eliezer de Souza da Silva et al.

Causal discovery (CD) algorithms are notably brittle when data is scarce, inferring unreliable causal relations that may contradict expert knowledge, especially when considering latent confounders. Furthermore, the lack of uncertainty quantification in most CD methods hinders users from diagnosing and refining results. To address these issues, we introduce Ancestral GFlowNets (AGFNs). AGFN samples ancestral graphs (AGs) proportionally to a score-based belief distribution representing our epistemic uncertainty over the causal relationships. Building upon this distribution, we propose an elicitation framework for expert-driven assessment. This framework comprises an optimal experimental design to probe the expert and a scheme to incorporate the obtained feedback into AGFN. Our experiments show that: i) AGFN is competitive against other methods that address latent confounding on both synthetic and real-world datasets; and ii) our design for incorporating feedback from a (simulated) human expert or a Large Language Model (LLM) improves inference quality.

Lukas Pfannschmidt, Christina Göpfert, Ursula Neumann et al.

Most existing feature selection methods are insufficient for analytic purposes as soon as high dimensional data or redundant sensor signals are dealt with since features can be selected due to spurious effects or correlations rather than causal effects. To support the finding of causal features in biomedical experiments, we hereby present FRI, an open source Python library that can be used to identify all-relevant variables in linear classification and (ordinal) regression problems. Using the recently proposed feature relevance method, FRI is able to provide the base for further general experimentation or in specific can facilitate the search for alternative biomarkers. It can be used in an interactive context, by providing model manipulation and visualization methods, or in a batch process as a filter method.

Maximilian Hahn, Alina Zajak, Dominik Heider et al.

Causal discovery across multiple datasets is often constrained by data privacy regulations and cross-site heterogeneity, limiting the use of conventional methods that require a single, centralized dataset. To address these challenges, we introduce fedCI, a federated conditional independence test that rigorously handles heterogeneous datasets with non-identical sets of variables, site-specific effects, and mixed variable types, including continuous, ordinal, binary, and categorical variables. At its core, fedCI uses a federated Iteratively Reweighted Least Squares (IRLS) procedure to estimate the parameters of generalized linear models underlying likelihood-ratio tests for conditional independence. Building on this, we develop fedCI-IOD, a federated extension of the Integration of Overlapping Datasets (IOD) algorithm, that replaces its meta-analysis strategy and enables, for the fist time, federated causal discovery under latent confounding across distributed and heterogeneous datasets. By aggregating evidence federatively, fedCI-IOD not only preserves privacy but also substantially enhances statistical power, achieving performance comparable to fully pooled analyses and mitigating artifacts from low local sample sizes. Our tools are publicly available as the fedCI Python package, a privacy-preserving R implementation of IOD, and a web application for the fedCI-IOD pipeline, providing versatile, user-friendly solutions for federated conditional independence testing and causal discovery.

Jan Benedikt Ruhland, Doguhan Bahcivan, Jan-Peter Sowa et al.

Recent advances in large language models made it possible to achieve high conversational performance with substantially reduced computational demands, enabling practical on-site deployment in clinical environments. Such progress allows for local integration of AI systems that uphold strict data protection and patient privacy requirements, yet their secure implementation in medicine necessitates careful consideration of ethical, regulatory, and technical constraints. In this study, we introduce MedChat, a locally deployable virtual physician framework that integrates an LLM-based medical chatbot with a diffusion-driven avatar for automated and structured anamnesis. The chatbot was fine-tuned using a hybrid corpus of real and synthetically generated medical dialogues, while model efficiency was optimized via Low-Rank Adaptation. A secure and isolated database interface was implemented to ensure complete separation between patient data and the inference process. The avatar component was realized through a conditional diffusion model operating in latent space, trained on researcher video datasets and synchronized with mel-frequency audio features for realistic speech and facial animation. Unlike existing cloud-based systems, this work demonstrates the feasibility of a fully offline, locally deployable LLM-diffusion framework for clinical anamnesis. The autoencoder and diffusion networks exhibited smooth convergence, and MedChat achieved stable fine-tuning with strong generalization to unseen data. The proposed system thus provides a privacy-preserving, resource-efficient foundation for AI-assisted clinical anamnesis, also in low-cost settings.

Jan Benedikt Ruhland, Thorsten Papenbrock, Jan-Peter Sowa et al.

Reliable detection of retinal diseases from fundus images is challenged by the variability in imaging quality, subtle early-stage manifestations, and domain shift across datasets. In this study, we systematically evaluated a Vision Transformer (ViT) classifier under multiple augmentation and enhancement strategies across several heterogeneous public datasets, as well as the AEyeDB dataset, a high-quality fundus dataset created in-house and made available for the research community. The ViT demonstrated consistently strong performance, with accuracies ranging from 0.789 to 0.843 across datasets and diseases. Diabetic retinopathy and age-related macular degeneration were detected reliably, whereas glaucoma remained the most frequently misclassified disease. Geometric and color augmentations provided the most stable improvements, while histogram equalization benefited datasets dominated by structural subtlety. Laplacian enhancement reduced performance across different settings. On the Papila dataset, the ViT with geometric augmentation achieved an AUC of 0.91, outperforming previously reported convolutional ensemble baselines (AUC of 0.87), underscoring the advantages of transformer architectures and multi-dataset training. To complement the classifier, we developed a GANomaly-based anomaly detector, achieving an AUC of 0.76 while providing inherent reconstruction-based explainability and robust generalization to unseen data. Probabilistic calibration using GUESS enabled threshold-independent decision support for future clinical implementation.

Ebenezer Awotoro, Chisom Ezekannagha, Florian Schwarz et al.

Structural biology has made significant progress in determining membrane proteins, leading to a remarkable increase in the number of available structures in dedicated databases. The inherent complexity of membrane protein structures, coupled with challenges such as missing data, inconsistencies, and computational barriers from disparate sources, underscores the need for improved database integration. To address this gap, we present MetaMP, a framework that unifies membrane-protein databases within a web application and uses machine learning for classification. MetaMP improves data quality by enriching metadata, offering a user-friendly interface, and providing eight interactive views for streamlined exploration. MetaMP was effective across tasks of varying difficulty, demonstrating advantages across different levels without compromising speed or accuracy, according to user evaluations. Moreover, MetaMP supports essential functions such as structure classification and outlier detection. We present three practical applications of Artificial Intelligence (AI) in membrane protein research: predicting transmembrane segments, reconciling legacy databases, and classifying structures with explainable AI support. In a validation focused on statistics, MetaMP resolved 77% of data discrepancies and accurately predicted the class of newly identified membrane proteins 98% of the time and overtook expert curation. Altogether, MetaMP is a much-needed resource that harmonizes current knowledge and empowers AI-driven exploration of membrane-protein architecture.

Adèle H. Ribeiro, Dominik Heider

Causal discovery is central to inferring causal relationships from observational data. In the presence of latent confounding, algorithms such as Fast Causal Inference (FCI) learn a Partial Ancestral Graph (PAG) representing the true model's Markov Equivalence Class. However, their correctness critically depends on empirical faithfulness, the assumption that observed (in)dependencies perfectly reflect those of the underlying causal model, which often fails in practice due to limited sample sizes. To address this, we introduce the first nonparametric score to assess a PAG's compatibility with observed data, even with mixed variable types. This score is both necessary and sufficient to characterize structural uncertainty and distinguish between distinct PAGs. We then propose data-compatible FCI (dcFCI), the first hybrid causal discovery algorithm to jointly address latent confounding, empirical unfaithfulness, and mixed data types. dcFCI integrates our score into an (Anytime)FCI-guided search that systematically explores, ranks, and validates candidate PAGs. Experiments on synthetic and real-world scenarios demonstrate that dcFCI significantly outperforms state-of-the-art methods, often recovering the true PAG even in small and heterogeneous datasets. Examining top-ranked PAGs further provides valuable insights into structural uncertainty, supporting more robust and informed causal reasoning and decision-making.

Julian Matschinske, Julian Späth, Reza Nasirigerdeh et al.

Machine Learning (ML) and Artificial Intelligence (AI) have shown promising results in many areas and are driven by the increasing amount of available data. However, this data is often distributed across different institutions and cannot be shared due to privacy concerns. Privacy-preserving methods, such as Federated Learning (FL), allow for training ML models without sharing sensitive data, but their implementation is time-consuming and requires advanced programming skills. Here, we present the FeatureCloud AI Store for FL as an all-in-one platform for biomedical research and other applications. It removes large parts of this complexity for developers and end-users by providing an extensible AI Store with a collection of ready-to-use apps. We show that the federated apps produce similar results to centralized ML, scale well for a typical number of collaborators and can be combined with Secure Multiparty Computation (SMPC), thereby making FL algorithms safely and easily applicable in biomedical and clinical environments.

Reihaneh Torkzadehmahani, Reza Nasirigerdeh, David B. Blumenthal et al.

Artificial intelligence (AI) has been successfully applied in numerous scientific domains. In biomedicine, AI has already shown tremendous potential, e.g. in the interpretation of next-generation sequencing data and in the design of clinical decision support systems. However, training an AI model on sensitive data raises concerns about the privacy of individual participants. For example, summary statistics of a genome-wide association study can be used to determine the presence or absence of an individual in a given dataset. This considerable privacy risk has led to restrictions in accessing genomic and other biomedical data, which is detrimental for collaborative research and impedes scientific progress. Hence, there has been a substantial effort to develop AI methods that can learn from sensitive data while protecting individuals' privacy. This paper provides a structured overview of recent advances in privacy-preserving AI techniques in biomedicine. It places the most important state-of-the-art approaches within a unified taxonomy and discusses their strengths, limitations, and open problems. As the most promising direction, we suggest combining federated machine learning as a more scalable approach with other additional privacy preserving techniques. This would allow to merge the advantages to provide privacy guarantees in a distributed way for biomedical applications. Nonetheless, more research is necessary as hybrid approaches pose new challenges such as additional network or computation overhead.

Sebastian Spänig, Agnes Emberger-Klein, Jan-Peter Sowa et al.

Artificial intelligence (AI) will pave the way to a new era in medicine. However, currently available AI systems do not interact with a patient, e.g., for anamnesis, and thus are only used by the physicians for predictions in diagnosis or prognosis. However, these systems are widely used, e.g., in diabetes or cancer prediction. In the current study, we developed an AI that is able to interact with a patient (virtual doctor) by using a speech recognition and speech synthesis system and thus can autonomously interact with the patient, which is particularly important for, e.g., rural areas, where the availability of primary medical care is strongly limited by low population densities. As a proof-of-concept, the system is able to predict type 2 diabetes mellitus (T2DM) based on non-invasive sensors and deep neural networks. Moreover, the system provides an easy-to-interpret probability estimation for T2DM for a given patient. Besides the development of the AI, we further analyzed the acceptance of young people for AI in healthcare to estimate the impact of such system in the future.