{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:09:43Z","timestamp":1788566983030,"version":"build-2803163510"},"reference-count":77,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"D3 4 H\u2014Digital Driven Diagnostics, prognostics and therapeutics for sustainable Health care","award":["PNC 0000001"],"award-info":[{"award-number":["PNC 0000001"]}]},{"name":"the National Plan for Complementary Investments to the NRRP","award":["CUP B53C22006100001"],"award-info":[{"award-number":["CUP B53C22006100001"]}]},{"name":"Neurogenomics: Genomic Mechanisms in Nervous System Pathophysiology","award":["DSB.AD007.376"],"award-info":[{"award-number":["DSB.AD007.376"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>To better understand the complexity of biological systems, research has shifted from a reductionist to a holistic approach, expanding the focus from single genes to a genome-scale view of gene activity and regulation. This is known as transcriptomics, a continuously growing field generating gene expression signatures from different technologies. A comparable paradigm shift has occurred in computational systems biology with the implementation of Artificial Intelligence (AI) learning models for gene expression analysis and integration. These models enable transcriptome-based profiling to address challenges of data heterogeneity, integration, and updating, assisting human intelligence and enhancing their ability to retrieve, analyze, integrate, and generate data recursively, thanks to their intrinsic predictive, inferential, reinforcement, and generative capabilities. Additionally, while scientists worldwide are still learning how to leverage AI methods that can maintain the human-in-the-loop, a new fundamental change is emerging: agentic AI, which can autonomously act and employ other AI methods to pursue its objectives. As a futuristic perspective, the proposed data analysis pipeline imagines agentic AI systems allowing the automated retrieval and pre-processing of heterogeneous transcriptomics data, analysis and integration with other omics datasets, performed with an incremental updating and recurrent analysis (IURA) model that could allow the detection of guideline updates (e.g., disease reclassification) and the generation of new hypotheses, such as candidate biomarkers or transcriptome\u2013phenotype correlations. Since personalized medicine could derive profound benefits from its use, this scenario also raises important considerations regarding the advantages and concerns associated with the use of scientific AI agents in research and clinical practice.<\/jats:p>","DOI":"10.3390\/jpm16040181","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T11:32:47Z","timestamp":1774611167000},"page":"181","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Artificial Intelligence in Transcriptomics: From Human-in-the-Loop to Agentic AI"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0180-3481","authenticated-orcid":false,"given":"Giulia","family":"Gentile","sequence":"first","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council (CNR-IRIB), Via P. Gaifami, 18, 95126 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Morello","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council (CNR-IRIB), Via P. Gaifami, 18, 95126 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"La Cognata","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council (CNR-IRIB), Via P. Gaifami, 18, 95126 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3745-9953","authenticated-orcid":false,"given":"Maria","family":"Guarnaccia","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council (CNR-IRIB), Via P. Gaifami, 18, 95126 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7590-1792","authenticated-orcid":false,"given":"Sebastiano","family":"Cavallaro","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council (CNR-IRIB), Via P. 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