biostudies-literatureMardinoglu ANational Research Foundation of Korea (NRF)Knut och Alice Wallenbergs StiftelseNational Research Foundation of KoreaKnut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)1147-1165https://www.ebi.ac.uk/biostudies/studies/S-EPMC12405541biostudies-literatureUnknown21(9)Generating longitudinal and multi-layered big biological data is crucial for effectively implementing artificial intelligence (AI) and systems biology approaches in characterising whole-body biological functions in health and complex disease states. Big biological data consists of multi-omics, clinical, wearable device, and imaging data, and information on diet, drugs, toxins, and other environmental factors. Given the significant advancements in omics technologies, human metabologenomics, and computational capabilities, several multi-omics studies are underway. Here, we first review the recent application of AI and systems biology in integrating and interpreting multi-omics data, highlighting their contributions to the creation of digital twins and the discovery of novel biomarkers and drMolecular systems biologyLongitudinal big biological data in the AI era.PMC12405541NRF-2023-R1A2C300343872254Turkez HUhlen MSrinivasulu VPHood LMardinoglu APalsson BOShong MNielsen JfalseLongitudinal big biological data in the AI era.Generating longitudinal and multi-layered big biological data is crucial for effectively implementing artificial intelligence (AI) and systems biology approaches in characterising whole-body biological functions in health and complex disease states. Big biological data consists of multi-omics, clinical, wearable device, and imaging data, and information on diet, drugs, toxins, and other environmental factors. Given the significant advancements in omics technologies, human metabologenomics, and computational capabilities, several multi-omics studies are underway. Here, we first review the recent application of AI and systems biology in integrating and interpreting multi-omics data, highlighting their contributions to the creation of digital twins and the discovery of novel biomarkers and dr2025-01-01T00:00:00Z2025 Sep2026-05-29T21:16:23.107Z2026-04-08T05:57:22.903ZS-EPMC124055414076483110.1038/s44320-025-00134-0