A Multi-Omics Transformer Foundation Model For Ai-Driven Early Cancer Detection Using cfDNA And cfRNA: Implications For Precision Oncology And Early Intervention In U.S. Healthcare Systems
Abstract
A non-invasive and scalable substitute for tissue biopsies is liquid biopsy-based cancer diagnosis using circulating tumor DNA (cfDNA) and RNA (cfRNA); however, appropriate integration of heterogeneous molecular signals is still a major obstacle. Using TCGA gene expression and copy number variation data, we present a Transformer-based multi-omics fusion framework for pan-cancer identification in this paper. The suggested method dynamically weights informative molecular properties and learns intricate cross-omics interactions using self-attention. A single representation was produced by preprocessing, normalizing, and combining the gene expression and copy number variation profiles of 5,408 tumor samples from 33 different cancer types. The Autoencoder, Multilayer Perceptron, Support Vector Machine, and Logistic Regression baselines were used to compare the model. The Transformer achieved an accuracy of 82.6%, an F1-score of 82.0%, and an AUC of 0.899, surpassing all other methods. The results of this study demonstrate that attention-based multi-omics integration is a powerful and reliable method for liquid biopsy-based cancer diagnosis, which encourages the creation of scalable, AI-powered precision oncology systems.
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- Abreu, R. da S., Ferreira, D. D. P., Araujo, N. S. de, Horita, S., Tilli, T. M., Degrave, W., Moreira, A. dos S., & Waghabi, M. C. (2026). Liquid biopsy in cancer diagnosis and prognosis: A paradigm shift in precision oncology. Frontiers in Molecular Biosciences, 12, Article 1708518. https://doi.org/10.3389/fmolb.2025.1708518
- Ana R Baião, Zhaoxiang Cai, Rebecca C Poulos, Phillip J Robinson, Roger R Reddel, Qing Zhong, Susana Vinga, Emanuel Gonçalves, A technical review of multi-omics data integration methods: from classical statistical to deep generative approaches, Briefings in Bioinformatics, Volume 26, Issue 4, July 2025, bbaf355, https://doi.org/10.1093/bib/bbaf355
- Ashik, A. A. M., Rahman, M. M., Hossain, E., Rahman, M. S., Islam, S., & Khan, S. I. (2023). Transforming U.S. Healthcare Profitability through Data-Driven Decision Making: Applications, Challenges, and Future Directions. European Journal of Medical and Health Research, 1(3), 116-125. https://doi.org/10.59324/ejmhr.2023.1(3).21
- Baião, A.R., Cai, Z., Poulos, R.C., Robinson, P.J., Reddel, R.R., Zhong, Q., Vinga, S. and Gonçalves, E., 2025. A technical review of multi-omics data integration methods: from classical statistical to deep generative approaches. Briefings in bioinformatics, 26(4), p.bbaf355.
- Duan, J., Gao, Q., Wang, Z., Cai, S., Fan, J., Wang, J., et al. (2026). Exploration of multi-omics liquid biopsy approaches for multi-cancer early detection: The PROMISE study. Journal of Molecular Diagnostics, 7(1), 100176. https://doi.org/10.1016/j.xinn.2025.101076
- Gonzalez Reymundez, A. (2020) Multi-omic pan-cancer data from TCGA. Mendeley Data, V2. doi:10.17632/r8p67nfjc8.2.
- Guria, Z. M., Morshed, N., Rahman, I., Dhar, S. R., & Sufian, M. A. (2025). Advancing global peace through inclusive economic development and the role of artificial intelligence in bridging socioeconomic divides. In Proceedings of the 2025 International Conference on Artificial Intelligence’s Future Implementations (ICAIFI) (pp. 100–105). IEEE. https://doi.org/10.1109/ICAIFI66942.2025.11326547
- Hossain, E., Ashik, A. A. M., Rahman, M. M., Khan, S. I., Rahman, M. S., & Islam, S. (2023). Big data and migration forecasting: Predictive insights into displacement patterns triggered by climate change and armed conflict. Journal of Computer Science and Technology Studies, 5(4): 265–274. https://doi.org/10.32996/jcsts.2023.5.4.27/.
- Hossain, E., Shital, K. P., Rahman, M. S., Islam, S., Khan, S. I., & Ashik, A. A. M. (2024). Machine learning-driven governance: Predicting the effectiveness of international trade policies through policy and governance analytics. Journal of Trends in Financial and Economics, 1(3), 50–62. https://doi.org/10.61784/jtfe3053. https://scholar.google.com/citations?view_op=view_citation&hl=en&user=iOJQX0sAAAAJ&sortby=pubdate&citation_for_view=iOJQX0sAAAAJ:4TOpqqG69KYC
- Islam, S., Hossain, E., Rahman, M. S., Rahman, M. M., Khan, S. I., & Ashik, A. A. M. (2023). Digital Transformation in SMEs: Unlocking Competitive Advantage through Business Intelligence and Data Analytics Adoption. 5 (6):177-186. https://doi.org/10.32996/jbms.2023.5.6.14
- Islam, S., Khan, S. I., Ashik, A. A. M., Hossain, E., Rahman, M. M., & Rahman, M. S. (2024). Big data in economic recovery: A policy-oriented study on data analytics for crisis management and growth planning. Journal of Computational Analysis and Applications (JoCAAA), 33(7), 2349–2367. Retrieved from https://www.eudoxuspress.com/index.php/pub/article/view/3338
- Juie, B. J. A., Kabir, J. U. Z., Ahmed, R. A., & Rahman, M. M. (2021). Evaluating the impact of telemedicine through analytics: Lessons learned from the COVID-19 era. Journal of Medical and Health Studies, 2(2), 161–174.https://doi.org/10.32996/jmhs.2021.2.2.19
- Khan, S. I., Rahman, M. S., Ashik, A. A. M., Islam, S., Rahman, M. M., & Hossain, E. (2024). Big Data and Business Intelligence for Supply Chain Sustainability: Risk Mitigation and Green Optimization in the Digital Era. European Journal of Management, Economics and Business, 1(3): 262-276. https://doi.org/10.59324/ejmeb.2024.1(3).23
- Kwon, H.-J., Park, U.-H., Goh, C. J., Park, D., Lim, Y. G., Lee, I. K., Do, W.-J., Lee, K. J., Kim, H., Yun, S.-Y., Joo, J., Min, N. Y., Lee, S., Um, S.-W., & Lee, M.-S. (2023). Enhancing Lung Cancer Classification through Integration of Liquid Biopsy Multi-Omics Data with Machine Learning Techniques. Cancers, 15(18), 4556. https://doi.org/10.3390/cancers15184556
- Liang X, Tang Q, Chen J, Wei Y. Liquid Biopsy: A Breakthrough Technology in Early Cancer Screening. Cancer Screen Prev. 2025;4(1):40-52. doi: 10.14218/CSP.2024.00031.
- Luo X, Xie S, Hong F, Li X, Wei Y, Zhou Y, Su W, Yang Y, Tang L, Dao F, Cai P, Lin H, Lai H, Lyu H. From multi-omics to deep learning: advances in cfDNA-based liquid biopsy for multi-cancer screening. Biomark Res. 2025 Nov 28;14(1):3. doi: 10.1186/s40364-025-00874-z.
- Mohib, M. M., Uddin, M. B., Rahman, M. M., Tirumalasetty, M. B., Al-Amin, M. M., Shimu, S. J., Alam, M. F., Arbee, S., Munmun, A. R., Akhtar, A., & Mohiuddin, M. S. (2025). Dysregulated Oxidative Stress Pathways in Schizophrenia: Integrating Single-Cell Transcriptomic and Human Biomarker Evidence. Psychiatry International, 6(3), 104. ttps://doi.org/10.3390/psychiatryint6030104
- Pushparaj, A. K., & Muthukumar, M. (2026). Deep Learning Architectures for Multi-Omics Data Integration: Bridging Biomarker Discovery and Clinical Translation. Preprints. https://doi.org/10.20944/preprints202601.1884.v1
- Rahman, M. M., Juie, B. J. A., Tisha, N. T., & Tanvir, A. (2022). Harnessing predictive analytics and machine learning in drug discovery, disease surveillance, and fungal research. Eurasia Journal of Science and Technology, 4(2), 28-35. https://doi.org/10.61784/ejst3099
- Rahman, M. M., Rahman, M. S., Islam, S., Khan, S. I., Ashik, A. A. M., Hossain, E., & Tanvir, A. (2025). Integrating data analytics into health informatics: Advancing equity, pharmaceutical outcomes, and public health decision-making. Eurasian Journal of Medicine and Oncology, 9(4), 284–295. https://doi.org/10.36922/EJMO025300319
- Ran, D., Li, J., Zhao, M., Du, L., Zhang, Y., & Zhu, J. (2025). Artificial intelligence integrates multi-omics data for precision stratification and drug resistance prediction in breast cancer. Frontiers in Oncology, 15, Article 1612474. https://doi.org/10.3389/fonc.2025.1612474.
- Rishad, S. S. I., Akter, N., Ahamed, A., Sufian, M. A., Rinky, A. I., & Rimi, N. N. (2025). Leveraging Machine Learning for Cancer Insights and Disease Predictions. In Proceedings of the 2025 IEEE International Conference on Data-Driven Social Change (ICDDSC-2025), Pakistan. IEEE.
- Sartori, F., Codicè, F., Caranzano, I., Rollo, C., Birolo, G., Fariselli, P., & Pancotti, C. (2025). A Comprehensive Review of Deep Learning Applications with Multi-Omics Data in Cancer Research. Genes, 16(6), 648. https://doi.org/10.3390/genes16060648
- Song S, Zhang X, Cui P, He W, Zhou J, Wang S, Xiong Y, Xu S, Lin X, Huang G, Tan X, Xu Q, Liu Y, Li Q, Yuan K, Feng M, Lai H, Yang H, Zhang S. Plasma cfDNA multi-omic biomarkers profiling for detection and stratification of gastric carcinoma. BMC Cancer. 2025;25(1):1003. doi: 10.1186/s12885-025-14409-0.
- Sufian, M. A., Rimon, S. M. T. H., Mosaddeque, A. I., Guria, Z. M., Morshed, N., & Ahamed, A. (2024). Leveraging machine learning for strategic business gains in the healthcare sector. In Proceedings of the 2024 International Conference on TVET Excellence & Development (ICTeD) (pp. 225–230). IEEE. https://doi.org/10.1109/ICTeD62334.2024.10844658
- Tanvir, A., Juie, B. J. A., Tisha, N. T., & Rahman, M. M. (2020). Synergizing big data and biotechnology for innovation in healthcare, pharmaceutical development, and fungal research. International Journal of Biological, Physical and Chemical Studies, 2(2), 23–32. https://doi.org/10.32996/ijbpcs.2020.2.2.4.
- Tanvir, A.; Jo, J.; Park, S.M. (2024). Targeting Glucose Metabolism: A Novel Therapeutic Approach for Parkinson’s Disease. Cells. 13, 1876. https://doi.org/10.3390/cells13221876
- Zhong, P., Bai, L., Hong, M., Ouyang, J., Wang, R., Zhang, X., & Chen, P. (2024). A Comprehensive Review on Circulating cfRNA in Plasma: Implications for Disease Diagnosis and Beyond. Diagnostics, 14(10), 1045. https://doi.org/10.3390/diagnostics14101045
- Zhou, S., Guan, C., Deng, S. et al. A novel sequence-based transformer model architecture for integrating multi-omics data in preterm birth risk prediction. npj Digit. Med. 8, 536 (2025). https://doi.org/10.1038/s41746-025-01942-2
- Zhu, H., Li, Z., Xie, K., Kassim, S. H., Cao, C., Huang, K., Lu, Z., Ma, C., Li, Y., Jiang, K., & Yin, L. (2026). Liquid Biopsy in Early Screening of Cancers: Emerging Technologies and New Prospects. Biomedicines, 14(1), 158. https://doi.org/10.3390/biomedicines14010158