Supervised deep learning with gene functional annotation for cell classification
Year: 2026
Type: article
Abstract: Gene-by-gene differential expression analysis is a widely used supervised approach for interpreting single-cell RNA-sequencing (scRNA-seq) data. However, modern scRNA-seq datasets often contain large numbers of cells, leading to the identification of many differentially expressed genes with extremely small p-values but negligible effect sizes, thus making biological interpretation difficult. To overcome this challenge, we developed Supervised Deep learning with gene functional ANnotation (SDAN), a method that integrates gene functional annotation information (e.g., protein-protein interaction) with gene-expression profiles through a graph neural network. SDAN identifies functionally coherent gene sets that optimally classify cells, and the resulting cell-level classification scores can be aggregated to make individual-level predictions. We evaluated SDAN alongside three representative existing methods in three real-data applications aimed at identifying gene sets associated with severe COVID-19, dementia, and cancer immunotherapy response. Across all applications, SDAN consistently outperformed the alternative approaches by achieving two objectives simultaneously: accurate outcome classification and clear assignment of genes to functionally related gene sets.
Source: PLoS Computational Biology
Authors: Zhexiao Lin, Yuanyuan Gao, Wei Sun
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: National Science and Technology Council, Deanship of Scientific Research, Imam Mohammed Ibn Saud Islamic University, Centre de Recherche sur les Systèmes Polymères et Composites à Haute Performance, Foundation for the National Institutes of Health, U.S. Department of Agriculture, United States Agency for International Development, Bill and Melinda Gates Foundation, John D. and Catherine T. MacArthur Foundation, American Heart Association, Breast Cancer Research Foundation, California Environmental Protection Agency, Alexander von Humboldt-Stiftung, University of Mississippi, Naito Foundation, Takeda Science Foundation, Novartis Foundation, Japan Agency for Medical Research and Development, China Association for Science and Technology, Kawano Masanori Memorial Public Interest Incorporated Foundation, UK Research and Innovation, Pfizer Health Research Foundation, Bloomberg Philanthropies, Ohio Supercomputer Center, Argenx, National Institute for Health and Care Research, Royal Society, Deutsche Forschungsgemeinschaft, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Canada Research Chairs, National Natural Science Foundation of China, Fundacja na rzecz Nauki Polskiej, Bundesministerium für Bildung und Forschung, Austrian Science Fund, Cancerfonden, Ministry of Trade, Industry and Energy, Ministry of Higher Education, Malaysia, Fonds Québécois de la Recherche sur la Nature et les Technologies, Inamori Foundation, Islamic Development Bank, Princess Nourah Bint Abdulrahman University, Mitacs, China Scholarship Council, Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Forskningsrådet om Hälsa, Arbetsliv och Välfärd, Astellas Foundation for Research on Metabolic Disorders, Bundesinstitut für Sportwissenschaft, SENSHIN Medical Research Foundation, Senri Life Science Foundation, Cardinal Tien Hospital, Islamic University of Madinah, National Institutes of Health, Directorate for Engineering, Johnson and Johnson, Natural Sciences and Engineering Research Council of Canada, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, Japan Society for the Promotion of Science, Instituto de Salud Carlos III, National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care Yorkshire and Humber, NIHR Cambridge Biomedical Research Centre, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, National Institute on Deafness and Other Communication Disorders, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, National Center for Research Resources, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Natural Science Foundation of Zhejiang Province, Intramural Research Program
OpenAlex ID: W7163028389