{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T07:17:03Z","timestamp":1793776623409,"version":"4.6.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Comput Sci"],"DOI":"10.1038\/s43588-026-01026-5","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:03:01Z","timestamp":1787734981000},"page":"954-970","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Longitudinal alignments and syntheses of multimodal clinical data for personalized medicine with the PULSE framework"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1250-3998","authenticated-orcid":false,"given":"Wei","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0354-1772","authenticated-orcid":false,"given":"Kai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haodi","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changxi","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1734-7214","authenticated-orcid":false,"given":"Fei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixing","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingzhou","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte L.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7801-1488","authenticated-orcid":false,"given":"Ieng","family":"Chong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Loupy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Oermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4116-6616","authenticated-orcid":false,"given":"Saleem A.","family":"Al Dajani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Gootenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar O.","family":"Abudayyeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim N.","family":"Gladyshev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2975-807X","authenticated-orcid":false,"given":"John E. J.","family":"Rasko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4549-1697","authenticated-orcid":false,"given":"Kang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the International Consortium of Digital Twins in Healthcare and Medicine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"1026_CR1","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1038\/s41551-025-01474-w","volume":"9","author":"J Wen","year":"2025","unstructured":"Wen, J. Towards a multi-organ, multi-omics medical digital twin. Nat. Biomed. Eng. 9, 1386\u20131389 (2025).","journal-title":"Nat. Biomed. Eng."},{"key":"1026_CR2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2308812120","volume":"121","author":"J Wang","year":"2024","unstructured":"Wang, J. et al. Accurate estimation of biological age and its application in disease prediction using a multimodal image Transformer system. Proc. Natl Acad. Sci. USA 121, e2308812120 (2024).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1026_CR3","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s42256-024-00974-9","volume":"7","author":"SJ Mataraso","year":"2025","unstructured":"Mataraso, S. J. et al. A machine learning approach to leveraging electronic health records for enhanced omics analysis. Nat. Mach. Intell. 7, 293\u2013306 (2025).","journal-title":"Nat. Mach. Intell."},{"key":"1026_CR4","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1038\/s41586-025-09686-5","volume":"648","author":"Q Gong","year":"2025","unstructured":"Gong, Q. et al. Multi-omic profiling reveals age-related immune dynamics in healthy adults. Nature 648, 696\u2013706 (2025).","journal-title":"Nature"},{"key":"1026_CR5","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1038\/s41591-024-03142-z","volume":"30","author":"J Carrasco-Zanini","year":"2024","unstructured":"Carrasco-Zanini, J. et al. Proteomic signatures improve risk prediction for common and rare diseases. Nat. Med. 30, 2489\u20132498 (2024).","journal-title":"Nat. Med."},{"key":"1026_CR6","doi-asserted-by":"publisher","first-page":"eadc9854","DOI":"10.1126\/scitranslmed.adc9854","volume":"15","author":"D De Francesco","year":"2023","unstructured":"De Francesco, D. et al. Data-driven longitudinal characterization of neonatal health and morbidity. Sci. Transl. Med. 15, eadc9854 (2023).","journal-title":"Sci. Transl. Med."},{"key":"1026_CR7","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1038\/s42255-024-01185-7","volume":"7","author":"J Tang","year":"2025","unstructured":"Tang, J. et al. Longitudinal serum proteome mapping reveals biomarkers for healthy ageing and related cardiometabolic diseases. Nat. Metab. 7, 166\u2013181 (2025).","journal-title":"Nat. Metab."},{"key":"1026_CR8","doi-asserted-by":"publisher","first-page":"102854","DOI":"10.1016\/j.ebiom.2020.102854","volume":"57","author":"T Dodig-Crnkovi\u0107","year":"2020","unstructured":"Dodig-Crnkovi\u0107, T. et al. Facets of individual-specific health signatures determined from longitudinal plasma proteome profiling. eBioMedicine 57, 102854 (2020).","journal-title":"eBioMedicine"},{"key":"1026_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23014-1","volume":"12","author":"TV Pyrkov","year":"2021","unstructured":"Pyrkov, T. V. et al. Longitudinal analysis of blood markers reveals progressive loss of resilience and predicts human lifespan limit. Nat. Commun. 12, 2765 (2021).","journal-title":"Nat. Commun."},{"key":"1026_CR10","unstructured":"Launch of world\u2019s most significant protein study set to usher in new understanding for medicine. UK Biobank https:\/\/www.ukbiobank.ac.uk\/news\/launch-of-worlds-most-significant-protein-study-set-to-usher-in-new-understanding-for-medicine\/ (2025)."},{"key":"1026_CR11","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/s41551-024-01324-1","volume":"9","author":"F Carrillo-Perez","year":"2024","unstructured":"Carrillo-Perez, F., Pizurica, M., Marchal, K. & Gevaert, O. Synthetic multimodal data modelling for data imputation. Nat. Biomed. Eng. 9, 421\u2013425 (2024).","journal-title":"Nat. Biomed. Eng."},{"key":"1026_CR12","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-016-3890-3","volume":"16","author":"ESL Pedersen","year":"2016","unstructured":"Pedersen, E. S. L., Danquah, I. H., Petersen, C. B. & Tolstrup, J. S. Intra-individual variability in day-to-day and month-to-month measurements of physical activity and sedentary behaviour at work and in leisure-time among Danish adults. BMC Public Health 16, 1222 (2016).","journal-title":"BMC Public Health"},{"key":"1026_CR13","doi-asserted-by":"publisher","first-page":"3369","DOI":"10.1038\/s41591-024-03214-0","volume":"30","author":"L Heumos","year":"2024","unstructured":"Heumos, L. et al. An open-source framework for end-to-end analysis of electronic health record data. Nat. Med. 30, 3369\u20133380 (2024).","journal-title":"Nat. Med."},{"key":"1026_CR14","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1038\/s41592-023-01909-9","volume":"20","author":"T Ashuach","year":"2023","unstructured":"Ashuach, T. et al. MultiVI: deep generative model for the integration of multimodal data. Nat. Methods 20, 1222\u20131231 (2023).","journal-title":"Nat. Methods"},{"key":"1026_CR15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2214414119","volume":"119","author":"J-H Du","year":"2022","unstructured":"Du, J.-H., Cai, Z. & Roeder, K. Robust probabilistic modeling for single-cell multimodal mosaic integration and imputation via scVAEIT. Proc. Natl Acad. Sci. USA 119, e2214414119 (2022).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1026_CR16","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1038\/s41587-023-02040-y","volume":"42","author":"Z He","year":"2024","unstructured":"He, Z. et al. Mosaic integration and knowledge transfer of single-cell multimodal data with MIDAS. Nat. Biotechnol. 42, 1594\u20131605 (2024).","journal-title":"Nat. Biotechnol."},{"key":"1026_CR17","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1038\/s41591-019-0414-6","volume":"25","author":"SM Sch\u00fcssler-Fiorenza Rose","year":"2019","unstructured":"Sch\u00fcssler-Fiorenza Rose, S. M. et al. A longitudinal big data approach for precision health. Nat. Med. 25, 792\u2013804 (2019).","journal-title":"Nat. Med."},{"key":"1026_CR18","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/s41586-025-09529-3","volume":"647","author":"A Shmatko","year":"2025","unstructured":"Shmatko, A. et al. Learning the natural history of human disease with generative transformers. Nature 647, 248\u2013256 (2025).","journal-title":"Nature"},{"key":"1026_CR19","doi-asserted-by":"publisher","first-page":"4225","DOI":"10.1038\/s41591-025-04006-w","volume":"31","author":"K Wang","year":"2025","unstructured":"Wang, K. et al. A full life cycle biological clock based on routine clinical data and its impact in health and diseases. Nat. Med. 31, 4225\u20134235 (2025).","journal-title":"Nat. Med."},{"key":"1026_CR20","doi-asserted-by":"publisher","first-page":"2977","DOI":"10.1038\/s41591-025-03856-8","volume":"31","author":"Y Li","year":"2025","unstructured":"Li, Y. et al. Large language model-based biological age prediction in large-scale populations. Nat. Med. 31, 2977\u20132990 (2025).","journal-title":"Nat. Med."},{"key":"1026_CR21","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1016\/j.cell.2020.04.045","volume":"181","author":"K Zhang","year":"2020","unstructured":"Zhang, K. et al. Clinically applicable AI system for accurate diagnosis, quantitative measurements, and prognosis of COVID-19 pneumonia using computed tomography. Cell 181, 1423\u20131433 (2020).","journal-title":"Cell"},{"key":"1026_CR22","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1016\/j.cell.2018.02.010","volume":"172","author":"DS Kermany","year":"2018","unstructured":"Kermany, D. S. et al. Identifying medical diagnoses and treatable diseases by image-based deep learning. Cell 172, 1122\u20131131 (2018).","journal-title":"Cell"},{"key":"1026_CR23","doi-asserted-by":"publisher","DOI":"10.1126\/science.adm7066","volume":"389","author":"IS Forrest","year":"2025","unstructured":"Forrest, I. S. et al. Machine learning-based penetrance of genetic variants. Science 389, eadm7066 (2025).","journal-title":"Science"},{"key":"1026_CR24","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.cell.2025.11.016","volume":"189","author":"JMJ Valanarasu","year":"2026","unstructured":"Valanarasu, J. M. J. et al. Multimodal AI generates virtual population for tumor microenvironment modeling. Cell 189, 386\u2013400 (2026).","journal-title":"Cell"},{"key":"1026_CR25","doi-asserted-by":"publisher","first-page":"100071","DOI":"10.1016\/j.crmeth.2021.100071","volume":"1","author":"K Minoura","year":"2021","unstructured":"Minoura, K., Abe, K., Nam, H., Nishikawa, H. & Shimamura, T. A mixture-of-experts deep generative model for integrated analysis of single-cell multiomics data. Cell Rep. Methods 1, 100071 (2021).","journal-title":"Cell Rep. Methods"},{"key":"1026_CR26","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","volume":"42","author":"Y Hao","year":"2024","unstructured":"Hao, Y. et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat. Biotechnol. 42, 293\u2013304 (2024).","journal-title":"Nat. Biotechnol."},{"key":"1026_CR27","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1038\/s41587-023-01766-z","volume":"42","author":"S Ghazanfar","year":"2024","unstructured":"Ghazanfar, S., Guibentif, C. & Marioni, J. C. Stabilized mosaic single-cell data integration using unshared features. Nat. Biotechnol. 42, 284\u2013292 (2024).","journal-title":"Nat. Biotechnol."},{"key":"1026_CR28","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/s41586-024-08264-5","volume":"637","author":"BH Foy","year":"2025","unstructured":"Foy, B. H. et al. Haematological setpoints are a stable and patient-specific deep phenotype. Nature 637, 430\u2013438 (2025).","journal-title":"Nature"},{"key":"1026_CR29","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1038\/s41591-021-01468-6","volume":"27","author":"NM Cohen","year":"2021","unstructured":"Cohen, N. M. et al. Personalized lab test models to quantify disease potentials in healthy individuals. Nat. Med. 27, 1582\u20131591 (2021).","journal-title":"Nat. Med."},{"key":"1026_CR30","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1038\/s41592-024-02303-9","volume":"21","author":"P Weiler","year":"2024","unstructured":"Weiler, P., Lange, M., Klein, M., Pe\u2019er, D. & Theis, F. CellRank 2: unified fate mapping in multiview single-cell data. Nat. Methods 21, 1196\u20131205 (2024).","journal-title":"Nat. Methods"},{"key":"1026_CR31","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13059-017-1382-0","volume":"19","author":"FA Wolf","year":"2018","unstructured":"Wolf, F. A., Angerer, P. & Theis, F. J. SCANPY: large-scale single-cell gene expression data analysis. Genome Biol. 19, 15 (2018).","journal-title":"Genome Biol."},{"key":"1026_CR32","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1038\/s41588-024-01711-z","volume":"56","author":"EB Madden","year":"2024","unstructured":"Madden, E. B. et al. Advancing genomics to improve health equity. Nat. Genet. 56, 752\u2013757 (2024).","journal-title":"Nat. Genet."},{"key":"1026_CR33","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1038\/s41591-024-03359-y","volume":"31","author":"J Wang","year":"2025","unstructured":"Wang, J. et al. Self-improving generative foundation model for synthetic medical image generation and clinical applications. Nat. Med. 31, 609\u2013617 (2025).","journal-title":"Nat. Med."},{"key":"1026_CR34","doi-asserted-by":"publisher","first-page":"129","DOI":"10.18865\/ed.30.S1.129","volume":"30","author":"DM Griffith","year":"2020","unstructured":"Griffith, D. M. Preface: precision medicine approaches to health disparities research. Ethn. Dis. 30, 129\u2013134 (2020).","journal-title":"Ethn. Dis."},{"key":"1026_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.patter.2024.101028","volume":"5","author":"K Zhang","year":"2024","unstructured":"Zhang, K. et al. Concepts and applications of digital twins in healthcare and medicine. Patterns 5, 101028 (2024).","journal-title":"Patterns"},{"key":"1026_CR36","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/s41586-023-06592-6","volume":"622","author":"BB Sun","year":"2023","unstructured":"Sun, B. B. Plasma proteomic associations with genetics and health in the UK Biobank. Nature 622, 329\u2013338 (2023).","journal-title":"Nature"},{"key":"1026_CR37","unstructured":"Why choose UK Biobank? UK BioBank https:\/\/www.ukbiobank.ac.uk\/enable-your-research (2026)."},{"key":"1026_CR38","doi-asserted-by":"publisher","unstructured":"Wu, W. et al. Longitudinal alignments and syntheses of multi-modal clinical data for personalized medicine with the PULSE framework. Zenodo https:\/\/doi.org\/10.5281\/zenodo.20555139 (2026).","DOI":"10.5281\/zenodo.20555139"}],"container-title":["Nature Computational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s43588-026-01026-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s43588-026-01026-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s43588-026-01026-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:03:22Z","timestamp":1790028202000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s43588-026-01026-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":38,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["1026"],"URL":"https:\/\/doi.org\/10.1038\/s43588-026-01026-5","relation":{},"ISSN":["2662-8457"],"issn-type":[{"value":"2662-8457","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]},"assertion":[{"value":"30 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"W.W., K.W. and K.Z. have filed patents related to this work (jurisdiction: international, PCT \u2013 Patent Cooperation Treaty; application no. PCT\/CN2025\/112123, filed with the China National Intellectual Property Administration as receiving office). All other authors declare no competing interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}