Lomas Redondo, AlbaSánchez Velázquez, Jose M.García Tejedor, Álvaro J.Sánchez–Arévalo Lobo, Víctor Javier2025-12-192025-12-192025-01Lomas Redondo, A, Sánchez Velázquez, J M, García Tejedor, Á J & Sánchez–Arévalo Lobo, V J 2025, 'Deep learning based deconvolution methods : A systematic review', Computational and Structural Biotechnology Journal, vol. 27, pp. 2544-2565. https://doi.org/10.1016/j.csbj.2025.05.0382001-0370PubMedCentral: PMC12205315https://hdl.handle.net/10641/6822Publisher Copyright: © 2025 The Author(s)Within this systematic review we examine the role of Artificial Intelligence (AI) and Deep Learning (DL) in the development of cellular deconvolution tools, with an special focus on their application to the analysis of transcriptomics data from RNA sequencing. We emphasize the critical importance of high–quality reference profiles for enhancing the accuracy of the discussed deconvolution methods, which is essential to determine cellular compositions in complex biological samples. To ensure the robustness of our work, we have applied a rigorous selection process following the Preferred Reporting Items for Systematic Reviews and Meta–Analysis (PRISMA) guidelines. Through the review process, we have identified several key research gaps, highlighting the necessity for standardized methodologies and the improvement of the interpretability of the models. Overall, we present a comprehensive, up to date overview of the different methodologies, datasets, and findings associated with DL–driven deconvolution tools, paving the way for future research and emphasizing the value of collaboration between computational and biological sciences.222977937enghttp://creativecommons.org/licenses/by-nc-nd/4.0/Artificial intelligenceCellular deconvolutionComputational biologyDeep learningNeural networkRNA–seqTranscriptomics datascRNA–seqBiotechnologyBiophysicsStructural BiologyBiochemistryGeneticsComputer Science ApplicationsJournal ArticleReviewYesyesreview articleopen access10.1016/j.csbj.2025.05.038https://www.scopus.com/pages/publications/105007801393https://www.scopus.com/pages/publications/105007801393#tab=citedBy