Autoencoders reveal polyunsaturated fatty acids (PUFA)-Related metabolic signature linked to cancer risk
Year: 2026
Type: article
Abstract: BACKGROUND: Metabolomics is a valuable tool for characterising biological mechanisms involved in cancer development, but produces complex datasets with intricate interdependencies. While linear dimension reduction techniques such as principal component analysis (PCA), have proven useful to summarise informative hidden patterns, biological evidence suggests metabolic relationships extend beyond linearity. Non-linear dimension reduction techniques, such as autoencoders (AEs), may identify more meaningful components. METHODS: We applied AEs and PCA to metabolomic data available for 5828 matched case-control pairs from 8 cancer-specific case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, and compared their performance. We evaluated the association between components identified by AEs and PCA with cancer risk, and explored the biological interpretation of components through their association with genetic factors and selected biomarkers. FINDINGS: PCA and AEs showed similar reconstruction performance. PCA's first component (PCA.1) captured phosphatidylcholines (PCs) as the primary source of variability and was associated with cancer risk. Conversely, AEs decomposed PC metabolism into two components, one of which exhibited a stronger association with cancer risk than PCA.1. Unlike PCA.1, this component was strongly associated with genetic variants mapping to the TMEM258 and FADS genes, key in polyunsaturated fatty acids (PUFA) biosynthesis and regulation. Consistently, the AE component demonstrated stronger associations with circulating omega-3 and omega-6 PUFA levels than PCA.1. INTERPRETATION: Linear methods remain adequate for general dimension reduction. However, AEs better captured specific pathways, identifying a component reflecting perturbations in PUFA metabolism associated with cancer risk. FUNDING: World Cancer Research Fund (IIG_FULL_2022_013).
Source: EBioMedicine
Authors: Marie Breeur, Joshua Atkins, Laia Peruchet-Noray, Lisa Bonheme, Nicolas Alcala, Laure Dossus, Mazda Jenab, Mattias Johansson, Sabina Rinaldi, Ruth C. Travis, Christian Bork, Christina C. Dahm, Anne Tjønneland, Anja Olsen, Sabine Naudin, Seehyun Park, Therese Truong, Verena Katzke, Charlotte Le Cornet, Matthias B. Schulze, Marcela Prada, Carlotta Sacerdote, Benedetta Bendinelli, Claudia Agnoli, Fabrizio Pasanisi, José María Gálvez-Navas, Marcela Guevara, Alicia K. Heath, James Yarmolinsky, Marc J. Gunter, Pietro Ferrari, Karl Smith-Byrne, Vivian Viallon
Institutions: University of Oxford, Centre international de recherche sur le cancer, Aalborg University Hospital, Aalborg University, Aarhus University, University of Copenhagen, Inserm, Université de Versailles Saint-Quentin-en-Yvelines, Centre de recherche en Epidémiologie et Santé des Populations, German Cancer Research Center, German Institute of Human Nutrition, Azienda Ospedaliera Citta' della Salute e della Scienza di Torino, Fondazione IRCCS Istituto Nazionale dei Tumori, Federico II University Hospital, University of Naples Federico II, Instituto de Investigación Biosanitaria de Granada, Centro de Investigación Biomédica en Red, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Andalusian School of Public Health, Instituto de Salud Pública de Navarra, Imperial College London
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,780
Funders: Foundation for Iranian Studies, World Health Organization, Compagnia di San Paolo, Universitetet i Tromsø, Kræftens Bekæmpelse, Deutsches Krebsforschungszentrum, Centre International de Recherche sur le Cancer, Skåne County Council's Research and Development Foundation, World Cancer Research Fund International, Cancer Research UK, National Institute for Health and Care Research, Imperial College London, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, ZonMw, Bundesministerium für Bildung und Forschung, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, Ministero della Salute, Karen Elise Jensens Fond, Ligue Contre le Cancer, Vetenskapsrådet, Ministère de l'Education Nationale, de l'Enseignement Superieur et de la Recherche, Associazione Italiana per la Ricerca sul Cancro, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, Fonds de Recherche en Santé Respiratoire, Junta de Andalucía, Ministero dell'Università e della Ricerca, Rollins School of Public Health, Medical Research Council, World Cancer Research Fund, Instituto de Salud Carlos III, NIHR Imperial Biomedical Research Centre, School of Public Health, Imperial College London
Awards: Aetiology of type 2 diabetes and related metabolic disorders, G1407060293, G2440589090, G3328679326, G3409252637, G3508323335, The EPIC-Norfolk prospective population study: biological and behavioural determinants of health and disease in an ageing population, G527520901, G5315906942, Etude Epidémiologique des Enfants de femmes de l'Education Nationale, G6848493935, G7240651115, EPIC-Oxford: benefits and risks of plant-based diets
OpenAlex ID: W7127308643