Network medicine-based epistasis detection in complex diseases: ready for quantum computing
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.
Authors
- Lars Wienbrandt (ORCID: https://orcid.org/0000-0001-5685-2032)
- Antonio Mandarino (ORCID: https://orcid.org/0000-0003-3745-5204)
- Klaus Bønnelykke (ORCID: https://orcid.org/0000-0003-2003-1018)
- Nina K. Wenke (ORCID: https://orcid.org/0000-0002-8031-6878)
- Laura Schulz (ORCID: https://orcid.org/0000-0002-4702-3440)
- Matthew Cloward (ORCID: https://orcid.org/0000-0003-4775-5286)
- David Ellinghaus (ORCID: https://orcid.org/0000-0002-4332-6110)
- Leon Schwartz (ORCID: https://orcid.org/0000-0001-8621-4146)
- Michele Grossi (ORCID: https://orcid.org/0000-0003-1718-1314)
- Gordon Grabert (ORCID: https://orcid.org/0000-0001-5499-9970)
- Héctor Climente-González (ORCID: https://orcid.org/0000-0002-3030-7471)
- Maximilian Harl (ORCID: https://orcid.org/0000-0001-7522-5296)
- Sung‐Gwon Lee (ORCID: https://orcid.org/0000-0002-0928-9950)
- Klaudia Adamowicz (ORCID: https://orcid.org/0000-0002-9418-4386)
- Luigi Iapichino (ORCID: https://orcid.org/0000-0003-3938-8973)
- Mathias Wilhelm (ORCID: https://orcid.org/0000-0002-9224-3258)
- Lena Maria Hackl (ORCID: https://orcid.org/0000-0001-7472-6224)
- Alessandra Di Pierro (ORCID: https://orcid.org/0000-0003-4173-7941)
- Markus Hoffmann (ORCID: https://orcid.org/0000-0002-1920-288X)
- Markus List
- Anders Gorm Pedersen (ORCID: https://orcid.org/0000-0001-9650-8965)
- Jakub Jankowski (ORCID: https://orcid.org/0000-0002-1661-079X)
- Mario Picciani (ORCID: https://orcid.org/0000-0003-0428-1703)
- Lothar Hennighausen (ORCID: https://orcid.org/0000-0001-8319-9841)
- Christian Hoffmann (ORCID: https://orcid.org/0009-0005-5352-9236)
- Kristel Van Steen (ORCID: https://orcid.org/0000-0001-9868-5033)
- Massimiliano Incudini (ORCID: https://orcid.org/0000-0002-9389-5370)
- Priscilla A. Furth (ORCID: https://orcid.org/0000-0003-3883-0715)
- Gyuhyeok Cho (ORCID: https://orcid.org/0000-0001-6785-616X)
- Nico Trummer (ORCID: https://orcid.org/0000-0002-4639-0935)
- Amelie Fritz (ORCID: https://orcid.org/0000-0002-2983-8056)
- Olga Tsoy (ORCID: https://orcid.org/0000-0002-7592-2080)
- Federico Melograna (ORCID: https://orcid.org/0000-0001-9117-9242)
- Tim Kacprowski (ORCID: https://orcid.org/0000-0002-5393-2413)
- Jan Baumbach (ORCID: https://orcid.org/0000-0002-0282-0462)
- Aakriti Acharya
- Leon Hafner (ORCID: https://orcid.org/0000-0002-2705-1727)
- Andreas Maier (ORCID: https://orcid.org/0000-0003-4408-0068)
- Evelyn Scheibling
- David B. Blumenthal (ORCID: https://orcid.org/0000-0001-8651-750X)
- Julian Poschenrieder (ORCID: https://orcid.org/0009-0004-5948-3892)
- Sylvie Baier (ORCID: https://orcid.org/0000-0002-9120-6279)
- Ingmar Lesch
- Simon Kayser
- Paul Wissenberg
- Hye‐Kyung Lee (ORCID: https://orcid.org/0000-0002-7785-5942)
- Michael Hartung (ORCID: https://orcid.org/0000-0002-3992-0125)
- Hunor Frey
Institutions
- Brigham Young University (US)
- Bavarian Academy of Sciences and Humanities (DE)
- Chonnam National University (KR)
- University of Verona (IT)
- University of Copenhagen (DK)
- University of Liège (BE)
- Universität Hamburg (DE)
- University of Southern Denmark (DK)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Georgetown University (US)
- Gentofte Hospital (DK)
- Christian-Albrechts-Universität zu Kiel (DE)
- Medizinische Hochschule Hannover (DE)
- ETH Zurich (CH)
- Gwangju Institute of Science and Technology (KR)
- University of Gdańsk (PL)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- Copenhagen Prospective Studies on Asthma in Childhood (DK)
- RIKEN Center for Advanced Intelligence Project (JP)
- Institute for Advanced Study (DE)
- Leibniz Supercomputing Centre (DE)
- Technical University of Munich (DE)
- European Organization for Nuclear Research (CH)
- Technische Universität Braunschweig (DE)
- Technical University of Denmark (DK)
- KU Leuven (BE)
Publication Details
- Journal
- Nucleic Acids Research
- Published
- 2024-08-23
- DOI
- https://doi.org/10.1093/nar/gkae697
- Citations
- 15
- Primary Topic
- Bioinformatics and Genomic Networks
- Type
- article
- Field-Weighted Citation Impact
- 3.51
Funders
- Wellcome Trust
- CERN
- Translational Genomics Research Institute
- Deutsche Forschungsgemeinschaft
- Fundacja na rzecz Nauki Polskiej
- Bundesministerium für Bildung und Forschung
- Technische Universität München
- Gauss Centre for Supercomputing
- Horizon 2020 Framework Programme
- Leibniz-Gemeinschaft
- Leibniz-Rechenzentrum
- National Institute of Diabetes and Digestive and Kidney Diseases