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Updated: Jun 6, 2025

High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method
Published on: May 21, 2018
Efficient Search Algorithms for Identifying Synergistic Associations in High-Dimensional Datasets
Cillian Hourican1, Jie Li1, Pashupati P Mishra2,3,4
1Computational Science Lab, Institute of Informatics, University of Amsterdam, 1012 WP Amsterdam, The Netherlands.
Abstract:
In recent years, there has been a notably increased interest in the study of multivariate interactions and emergent higher-order dependencies. This is particularly evident in the context of identifying synergistic sets, which are defined as combinations of elements whose joint interactions result in the emergence of information that is not present in any individual subset of those elements. The scalability of frameworks such as partial information decomposition (PID) and those based on multivariate extensions of mutual information, such as O-information, is limited by combinational explosion in the number of sets that must be assessed. In order to address these challenges, we propose a novel approach that utilises stochastic search strategies in order to identify synergistic triplets within datasets. Furthermore, the methodology is extensible to larger sets and various synergy measures. By employing stochastic search, our approach circumvents the constraints of exhaustive enumeration, offering a scalable and efficient means to uncover intricate dependencies. The flexibility of our method is illustrated through its application to two epidemiological datasets: The Young Finns Study and the UK Biobank Nuclear Magnetic Resonance (NMR) data. Additionally, we present a heuristic for reducing the number of synergistic sets to analyse in large datasets by excluding sets with overlapping information. We also illustrate the risks of performing a feature selection before assessing synergistic information in the system.
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