In recent decades, the development of new drugs has become increasingly expensive and inefficient, and the molecular mechanisms of most pharmaceuticals remain poorly understood. In response, computational systems and network medicine tools have emerged to identify potential drug repurposing candidates. However, these tools often require complex installation and lack intuitive visual network mining capabilities. To tackle these challenges, we introduce Drugst.One, a platform that assists specialized computational medicine tools in becoming user-friendly, web-based utilities for drug repurposing. With just three lines of code, Drugst.One turns any systems biology software into an interactive web tool for modeling and analyzing complex protein-drug-disease networks. Demonstrating its broad adaptability, Drugst.One has been successfully integrated with 21 computational systems medicine tools. Available at https://drugst.one, Drugst.One has significant potential for streamlining the drug discovery process, allowing researchers to focus on essential aspects of pharmaceutical treatment research.

Up to 6% of the global population is estimated to be affected by one of about 10,000 distinct rare diseases (RDs). RDs are, to this day, often not understood, and thus, patients are heavily underserved. Most RD studies are chronically underfunded, and research faces inherent difficulties in analyzing scarce data. Furthermore, the creation and analysis of representative datasets are often constrained by stringent data protection regulations, such as the EU General Data Protection Regulation. This review examines the potential of federated learning (FL) as a privacy-by-design approach to training machine learning on distributed datasets while ensuring data privacy by maintaining the local patient data and only sharing model parameters, which is particularly beneficial in the context of sensitive data that cannot be collected in a centralized manner. FL enhances model accuracy by leveraging diverse datasets without compromising data privacy. This is particularly relevant in rare diseases, where heterogeneity and small sample sizes impede the development of robust models. FL further has the potential to enable the discovery of novel biomarkers, enhance patient stratification, and facilitate the development of personalized treatment plans. This review illustrates how FL can facilitate large-scale, cross-institutional collaboration, thereby enabling the development of more accurate and generalizable models for improved diagnosis and treatment of rare diseases. However, challenges such as non-independently distributed data and significant computational and bandwidth requirements still need to be addressed. Future research must focus on applying FL technology for rare disease datasets while exploring standardized protocols for cross-border collaborations that can ultimately pave the way for a new era of privacy-preserving and distributed data-driven rare disease research.

Most heritable diseases are polygenic. To comprehend the underlying genetic architecture, it is crucial to discover the clinically relevant epistatic interactions (EIs) between genomic single nucleotide polymorphisms (SNPs) ( 1–3). Existing statistical computational methods for EI detection are mostly limited to pairs of SNPs due to the combinatorial explosion of higher-order EIs. With NeEDL (network-based epistasis detection via local search), we leverage network medicine to inform the selection of EIs that are an order of magnitude more statistically significant compared to existing tools and consist, on average, of five SNPs. We further show that this computationally demanding task can be substantially accelerated once quantum computing hardware becomes available. We apply NeEDL to eight different diseases and discover genes (affected by EIs of SNPs) that are partly known to affect the disease, additionally, these results are reproducible across independent cohorts. EIs for these eight diseases can be interactively explored in the Epistasis Disease Atlas (https://epistasis-disease-atlas.com). In summary, NeEDL demonstrates the potential of seamlessly integrated quantum computing techniques to accelerate biomedical research. Our network medicine approach detects higher-order EIs with unprecedented statistical and biological evidence, yielding unique insights into polygenic diseases and providing a basis for the development of improved risk scores and combination therapies.

A long-term objective of network medicine is to replace our current, mainly phenotype-based disease definitions by subtypes of health conditions corresponding to distinct pathomechanisms. For this, molecular and health data are modeled as networks and are mined for pathomechanisms. However, many such studies rely on large-scale disease association data where diseases are annotated using the very phenotype-based disease definitions the network medicine field aims to overcome. This raises the question to which extent the biases mechanistically inadequate disease annotations introduce in disease association data distort the results of studies which use such data for pathomechanism mining. We address this question using global- and local-scale analyses of networks constructed from disease association data of various types. Our results indicate that large-scale disease association data should be used with care for pathomechanism mining and that analyses of such data should be accompanied by close-up analyses of molecular data for well-characterized patient cohorts.