ObjectiveTo facilitate clinical/genomic/biomedical research, constructing generalizable predictive models using cross-institutional methods while protecting privacy is imperative. However, state-of-the-art methods assume a "flattened" topology, while real-world research networks may consist of "network-of-networks" which can imply practical issues including training on small data for rare diseases/conditions, prioritizing locally trained models, and maintaining models for each level of the hierarchy. In this study, we focus on developing a hierarchical approach to inherit the benefits of the privacy-preserving methods, retain the advantages of adopting blockchain, and address practical concerns on a research network-of-networks.Materials and methodsWe propose a framework to combine level-wise model learning, blockchain-based model dissemination, and a novel hierarchical consensus algorithm for model ensemble. We developed an example implementation HierarchicalChain (hierarchical privacy-preserving modeling on blockchain), evaluated it on 3 healthcare/genomic datasets, as well as compared its predictive correctness, learning iteration, and execution time with a state-of-the-art method designed for flattened network topology.ResultsHierarchicalChain improves the predictive correctness for small training datasets and provides comparable correctness results with the competing method with higher learning iteration and similar per-iteration execution time, inherits the benefits of the privacy-preserving learning and advantages of blockchain technology, and immutable records models for each level.DiscussionHierarchicalChain is independent of the core privacy-preserving learning method, as well as of the underlying blockchain platform. Further studies are warranted for various types of network topology, complex data, and privacy concerns.ConclusionWe demonstrated the potential of utilizing the information from the hierarchical network-of-networks topology to improve prediction
