Jan Baumbach

Simon Süwer, Zoe Chervontseva, Kester Bagemihl et al.

The rapid growth of scientific software has created practical barriers for bioinformatics research. Although powerful statistical, artificial intelligence (AI)-based methods are now widely available, their effective use is often hindered by fragmented distribution, inconsistent documentation, complex dependencies, and difficult-to-reproduce execution environments. As a result, reusing published tools and workflow adaptation to own date remains technically demanding and time-intensive, even for experienced users. Here, we present PoSyMed, an open and modular platform for the controlled integration, composition, and execution of bioinformatics tools and workflows. PoSyMed combines a backend-centered platform architecture with formal tool descriptions, controlled container-based build and execution processes, persistent workflow state, and a dialogue-based user interface. Large language models (LLM) are integrated not as autonomous decision-makers, but as human-computer interface with bounded semantic assistants that help identify tools, propose workflow steps, and support parameterization within a typed, validated, and human-supervised execution environment. PoSyMed is designed to improve reproducibility, traceability, and transparency in practical biomedical analysis within one platform. We describe the system architecture and evaluate its behavior across representative biological software scenarios with respect to workflow support, interaction design, and platform extensibility. PoSyMed is publicly available at https://apps.cosy.bio/posymed.

Michael Hartung, Andreas Maier, Yuliya Burankova et al.

Unsupervised patient stratification is essential for disease subtype discovery, yet, despite growing evidence of molecular heterogeneity of non-oncological diseases, popular methods are benchmarked primarily using cancers with mutually exclusive molecular subtypes well-differentiated by numerous biomarkers. Evaluating 22 unsupervised methods, including clustering and biclustering, using simulated and real transcriptomics data revealed their inefficiency in scenarios with non-mutually exclusive subtypes or subtypes discriminated only by few biomarkers. To address these limitations and advance precision medicine, we developed UnPaSt, a novel biclustering algorithm for unsupervised patient stratification based on differentially expressed biclusters. UnPaSt outperformed widely used patient stratification approaches in the de novo identification of known subtypes of breast cancer and asthma. In addition, it detected many biologically insightful patterns across bulk transcriptomics, proteomics, single-cell, spatial transcriptomics, and multi-omics datasets, enabling a more nuanced and interpretable view of high-throughput data heterogeneity than traditionally used methods.

Reza Nasirigerdeh, Reihaneh Torkzadehmahani, Julian Matschinske et al.

Federated learning (FL) enables multiple clients to jointly train a global model under the coordination of a central server. Although FL is a privacy-aware paradigm, where raw data sharing is not required, recent studies have shown that FL might leak the private data of a client through the model parameters shared with the server or the other clients. In this paper, we present the HyFed framework, which enhances the privacy of FL while preserving the utility of the global model. HyFed provides developers with a generic API to develop federated, privacy-preserving algorithms. HyFed supports both simulation and federated operation modes and its source code is publicly available at https://github.com/tum-aimed/hyfed.

Keyvan RahimiZadeh, Ahmad Taheri, Jan Baumbach et al.

Lithology discrimination is a crucial activity in characterizing oil reservoirs, and processing lithology microscopic images is an essential technique for investigating fossils and minerals and geological assessment of shale oil exploration. In this way, Deep Learning (DL) technique is a powerful approach for building robust classifier models. However, there is still a considerable challenge to collect and produce a large dataset. Transfer-learning and data augmentation techniques have emerged as popular approaches to tackle this problem. Furthermore, due to different reasons, especially data privacy, individuals, organizations, and industry companies often are not willing to share their sensitive data and information. Federated Learning (FL) has emerged to train a highly accurate central model across multiple decentralized edge servers without transferring sensitive data, preserving sensitive data, and enhancing security. This study involves two phases; the first phase is to conduct Lithology microscopic image classification on a small dataset using transfer learning. In doing so, various pre-trained DL model architectures are comprehensively compared for the classification task. In the second phase, we formulated the classification task to a Federated Transfer Learning (FTL) scheme and proposed a Fine-Tuned Aggregation strategy for Federated Learning (FTA-FTL). In order to perform a comprehensive experimental study, several metrics such as accuracy, f1 score, precision, specificity, sensitivity (recall), and confusion matrix are taken into account. The results are in excellent agreement and confirm the efficiency of the proposed scheme, and show that the proposed FTA-FTL algorithm is capable enough to achieve approximately the same results obtained by the centralized implementation for Lithology microscopic images classification task.

M. Rafiei, S. Das, M. Bakhtiari et al.

Knee osteoarthritis (OA) is a widespread chronic condition that impairs mobility and diminishes quality of life. Despite the proven benefits of exercise therapy and patient education in managing the OA symptoms pain and functional limitations, these strategies are often underutilized. Personalized outcome prediction models can help motivate and engage patients, but the accuracy of existing models in predicting changes in knee pain remains insufficiently examined. To validate existing models and introduce a concise personalized model predicting changes in knee pain before to after participating in a supervised education and exercise therapy program (GLA:D) for knee OA patients. Our models use self-reported patient information and functional measures. To refine the number of variables, we evaluated the variable importance and applied clinical reasoning. We trained random forest regression models and compared the rate of true predictions of our models with those utilizing average values. We evaluated the performance of a full, continuous, and concise model including all 34, all 11 continuous, and the six most predictive variables respectively. All three models performed similarly and were comparable to the existing model, with R-squares of 0.31-0.32 and RMSEs of 18.65-18.85 - despite our increased sample size. Allowing a deviation of 15 VAS points from the true change in pain, our concise model and utilizing the average values estimated the change in pain at 58% and 51% correctly, respectively. Our supplementary analysis led to similar outcomes. Our concise personalized prediction model more accurately predicts changes in knee pain following the GLA:D program compared to average pain improvement values. Neither the increase in sample size nor the inclusion of additional variables improved previous models. To improve predictions, new variables beyond those in the GLA:D are required.

Simon Süwer, Kester Bagemihl, Sylvie Baier et al.

Repurposing approved drugs offers a time-efficient and cost-effective alternative to traditional drug development. However, in silico prediction of repurposing candidates is challenging and requires the effective collaboration of specialists in various fields, including pharmacology, medicine, biology, and bioinformatics. Fragmented, specialized algorithms and tools often address only narrow aspects of the overall problem. Heterogeneous, unstructured data landscapes require the expertise of specialized users. Hence, these data services do not integrate smoothly across workflows. With ChatDRex, we present a conversation-based, multi-agent system that facilitates the execution of complex bioinformatic analyses aiming for network-based drug repurposing prediction. It builds on the integrated systems medicine knowledge graph (NeDRex KG). ChatDRex provides natural language access to its extensive biomedical knowledge base. It integrates bioinformatics agents for network analysis, literature mining, and drug repurposing. These are complemented by agents that evaluate functional coherence for in silico validation. Its flexible multi-agent design assigns specific tasks to specialized agents, including query routing, data retrieval, algorithm execution, and result visualization. A dedicated reasoning module keeps the user in the loop and allows for hallucination detection. By enabling physicians and researchers without computer science expertise to control complex analyses with natural language, ChatDRex democratizes access to bioinformatics as an important resource for drug repurposing. It enables clinical experts to generate hypotheses and explore drug repurposing opportunities, ultimately accelerating the discovery of novel therapies and advancing personalized medicine and translational research. ChatDRex is publicly available at apps.cosy.bio/chatdrex.

Yuliya Burankova, Julian Klemm, Jens J. G. Lohmann et al.

Batch effects in omics data obscure true biological signals and constitute a major challenge for privacy-preserving analyses of distributed patient data. Existing batch effect correction methods either require data centralization, which may easily conflict with privacy requirements, or lack support for missing values and automated workflows. To bridge this gap, we developed fedRBE, a federated implementation of limma's removeBatchEffect method. We implemented it as an app for the FeatureCloud platform. Unlike its existing analogs, fedRBE effectively handles data with missing values and offers an automated, user-friendly online user interface (https://featurecloud.ai/app/fedrbe). Leveraging secure multi-party computation provides enhanced security guarantees over classical federated learning approaches. We evaluated our fedRBE algorithm on simulated and real omics data, achieving performance comparable to the centralized method with negligible differences (no greater than 3.6E-13). By enabling collaborative correction without data sharing, fedRBE facilitates large-scale omics studies where batch effect correction is crucial.

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.

Reza Nasirigerdeh, Mohammad Bakhtiari, Reihaneh Torkzadehmahani et al.

Federated learning has faced performance and network communication challenges, especially in the environments where the data is not independent and identically distributed (IID) across the clients. To address the former challenge, we introduce the federated-centralized concordance property and show that the federated single-mini-batch training approach can achieve comparable performance as the corresponding centralized training in the Non-IID environments. To deal with the latter, we present the federated multi-mini-batch approach and illustrate that it can establish a trade-off between the performance and communication efficiency and outperforms federated averaging in the Non-IID settings.

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.