Explainable artificial intelligence for multi-modal cancer analysis: from genomics to immunology
Abstract
Cancer remains one of the most biologically intricate and heterogeneous diseases, with variability spanning genetic, epigenetic, metabolic, spatial, and immunological dimensions. This multifactorial complexity is shaped by tumor-microenvironment interactions, immune modulation, clonal evolution, and therapeutic pressures, creating profound challenges for accurate prognosis, treatment selection, and durable response prediction. Conventional single-modality analytical approaches often capture only isolated features of this landscape, limiting their ability to generalize across patient populations and clinical settings. Selective multimodal deep learning (MDL) provides a transformative framework by mechanism-informed integration of complementary biomedical data-including genomics, transcriptomics, histopathology, medical imaging, proteomics, metabolomics, electronic health records (EHRs), and immunological profiles into unified models capable of capturing cross-scale dependencies and emergent patterns, while mitigating interference through targeted fusion strategies. The interpretability of these models is enhanced by explainable artificial intelligence (XAI), which translates complex computational predictions into transparent, biologically grounded explanations that align with known oncological and immunological processes. A distinctive focus of this review is immunology-informed integration, which connects predictive signatures to tumor-immune microenvironment dynamics, enhanc…
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Most XAI systems in multi-omics oncology apply a single explanation method to the model's final output without distinguishing the explanatory contribution of each biological stratum.
“Most XAI systems in multi-omics oncology apply a single explanation method to the model’s final output without distinguishing the explanatory contribution of each biological stratum”
From A generative AI multi-agent framework with integrated XAI governance for cancer diagnostics: from multi-omics interpretation to lifestyle risk stratification (2026) · cites this paper as Zhang and Yin, 2025
A Graph Neural Network paired with GNNExplainer identifies network subgraphs whose activation most strongly influences cancer risk prediction.
“a Graph Neural Network architecture is paired with GNNExplainer to identify the network subgraphs whose activation most strongly influences the cancer risk prediction”
From A generative AI multi-agent framework with integrated XAI governance for cancer diagnostics: from multi-omics interpretation to lifestyle risk stratification (2026) · cites this paper as Zhang and Yin, 2025
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Wysocki, O., Mak, S., Frost, H., Graham, D. M., Landers, D., & Aslam, T. M. (2025) · International Journal of Medical Informatics · doi:10.1016/j.ijmedinf.2025.105958 · Cited by 4 · see citing works
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Mechanistically Explainable AI Model for Predicting Synergistic Cancer Therapy Combinations
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Chakrabarti, T., & Lee, M. (2026) · Cancers · doi:10.3390/cancers18081281 · Cited by 3 · see citing works
Polit, F., Bahmad, H. F., Kassab, M. B., Elajami, M. K., Recine, M. A., Alghamdi, S., & Poppiti, R. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1833926 · Cited by 3 · see citing works
Barki, C., Chouchen, M., Sediri, A., Ceylan, H. İ., Rahmouni, H. B., Muntean, R. I., El-Seedi, H. R., Bragazzi, N. L., & Dergaa, I. (2026) · Frontiers in Systems Biology · doi:10.3389/fsysb.2026.1892418 · Cited by 1 · see citing works
Zhao, X., Liu, Z., Yang, J., Xie, Q., Mao, T., Heng, Z., Wang, H., Zheng, P., Jiang, K., & Gao, F. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1896755 · Cited by 1 · see citing works
Bahmad, H. F., Mirzabeigi, Y., Elajami, Y. K., Abou-Kheir, W. G., & Nair, N. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1801005 · Cited by 1 · see citing works
Rehman, A. U., Sayyed, A., Mohmand, M. I., Rathore, S. A., Khan, M. M., & Iqbal, A. (2026) · Scientific Reports · doi:10.1038/s41598-026-66642-7 · Cited by 1 · see citing works
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Hey, G. E., Sesto, M., Still, M., Patel, G., Crlenjak, N., Dagra, A., Wu, Y., Guo, Y., & Ghiaseddin, A. P. (2026) · Journal of Neuro-Oncology · doi:10.1007/s11060-026-05774-2
- Authors
- Zhang, M., & Yin, L.
- Affiliations
- Shandong Management University (CN)
- Corresponding author
- Zhang, Min
- ORCID
- Zhang, Min
- Venue
- Critical Reviews in Oncology/Hematology
- Publisher
- Elsevier BV
- Published
- 2026-03
- Volume
- 219
- Pages
- 105040
- ISSN
- 1040-8428 (ISSN-L)
- OpenAlex
- W4416556358
- Cited by
- 5
- References
- 202
- Citations by year
- 2026: 5
- FWCI
- 0.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Critical Reviews in Oncology/Hematology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Computer Science › Artificial Intelligence › Explainable Artificial Intelligence (XAI)
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiomics and Machine Learning in Medical Imaging
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- explainable AI, multimodal deep learning, cancer, tumor immune microenvironment, multimodal fusion, precision oncology, biomarker discovery, data harmonization, modality imbalance, federated learning, causal inference, model interpretability
- MeSH terms
- Deep Learning, Artificial Intelligence, Humans, Immunotherapy, Neoplasms, Biomarkers, Tumor, Genomics, Precision Medicine, Tumor Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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