Multimodal Neurodegenerative Disease Subtyping Explained by ChatGPT (2402.00137v1)
Abstract: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease; yet its currently available treatments are limited to stopping disease progression. Moreover, effectiveness of these treatments is not guaranteed due to the heterogenetiy of the disease. Therefore, it is essential to be able to identify the disease subtypes at a very early stage. Current data driven approaches are able to classify the subtypes at later stages of AD or related disorders, but struggle when predicting at the asymptomatic or prodromal stage. Moreover, most existing models either lack explainability behind the classification or only use a single modality for the assessment, limiting scope of its analysis. Thus, we propose a multimodal framework that uses early-stage indicators such as imaging, genetics and clinical assessments to classify AD patients into subtypes at early stages. Similarly, we build prompts and use LLMs, such as ChatGPT, to interpret the findings of our model. In our framework, we propose a tri-modal co-attention mechanism (Tri-COAT) to explicitly learn the cross-modal feature associations. Our proposed model outperforms baseline models and provides insight into key cross-modal feature associations supported by known biological mechanisms.
- A. Association, “2022 Alzheimer’s disease facts and figures,” Alzheimer’s & Dementia, vol. 18, no. 4, pp. 700–789, 2022.
- A. Mitelpunkt et al., “Novel Alzheimer’s disease subtypes identified using a data and knowledge driven strategy,” Scientific Reports, vol. 10, no. 1, p. 1327, Jan. 2020, number: 1 Publisher: Nature Publishing Group.
- A. Badhwar et al., “A multiomics approach to heterogeneity in Alzheimer’s disease: focused review and roadmap,” Brain, vol. 143, no. 5, pp. 1315–1331, May 2020.
- G. Martí-Juan et al., “Revealing heterogeneity of brain imaging phenotypes in Alzheimer’s disease based on unsupervised clustering of blood marker profiles,” PLOS ONE, vol. 14, no. 3, p. e0211121, Mar. 2019, publisher: Public Library of Science.
- Y. Feng, et al., “Deep multiview learning to identify imaging-driven subtypes in mild cognitive impairment,” BMC Bioinformatics, vol. 23, no. 3, p. 402, Sep. 2022.
- M. A. Emon et al., “Clustering of Alzheimer’s and Parkinson’s disease based on genetic burden of shared molecular mechanisms,” Scientific Reports, vol. 10, no. 1, p. 19097, Nov. 2020.
- J. Wen, et al., “Multi-scale semi-supervised clustering of brain images: Deriving disease subtypes,” Medical Image Analysis, vol. 75, p. 102304, Jan. 2022.
- K. Poulakis et al., “Multi-cohort and longitudinal Bayesian clustering study of stage and subtype in Alzheimer’s disease,” Nature Communications, vol. 13, no. 1, p. 4566, aug 2022, number: 1 Publisher: Nature Publishing Group.
- A. Dadu et al., “Identification and prediction of Parkinson’s disease subtypes and progression using machine learning in two cohorts,” npj Parkinson’s Disease, vol. 8, no. 1, pp. 1–12, Dec. 2022, number: 1 Publisher: Nature Publishing Group.
- C. Su, et al., “Integrative analyses of multimodal clinical, neuroimaging, genetic, and transcriptomic data identify subtypes and potential treatments for heterogeneous Parkinson’s disease progression,” Oct. 2022, pages: 2021.07.18.21260731.
- N. D. Nguyen and D. Wang, “Multiview learning for understanding functional multiomics,” PLOS Computational Biology, vol. 16, no. 4, p. e1007677, Apr. 2020, publisher: Public Library of Science.
- S.-C. Huang, A. Pareek, S. Seyyedi, I. Banerjee, and M. P. Lungren, “Fusion of medical imaging and electronic health records using deep learning: a systematic review and implementation guidelines,” NPJ Digital Medicine, vol. 3, p. 136, Oct. 2020. [Online]. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567861/
- J.-B. Alayrac, J. Donahue, P. Luc, A. Miech, I. Barr, Y. Hasson, K. Lenc, A. Mensch, K. Millican, M. Reynolds, R. Ring, E. Rutherford, S. Cabi, T. Han, Z. Gong, S. Samangooei, M. Monteiro, J. Menick, S. Borgeaud, A. Brock, A. Nematzadeh, S. Sharifzadeh, M. Binkowski, R. Barreira, O. Vinyals, A. Zisserman, and K. Simonyan, “Flamingo: a Visual Language Model for Few-Shot Learning,” Nov. 2022, arXiv:2204.14198 [cs]. [Online]. Available: http://arxiv.org/abs/2204.14198
- H. Akbari, L. Yuan, R. Qian, W.-H. Chuang, S.-F. Chang, Y. Cui, and B. Gong, “VATT: Transformers for Multimodal Self-Supervised Learning from Raw Video, Audio and Text,” Dec. 2021, arXiv:2104.11178 [cs, eess]. [Online]. Available: http://arxiv.org/abs/2104.11178
- R. J. Chen, M. Y. Lu, W.-H. Weng, T. Y. Chen, D. F. K. Williamson, T. Manz, M. Shady, and F. Mahmood, “Multimodal Co-Attention Transformer for Survival Prediction in Gigapixel Whole Slide Images,” in 2021 IEEE/CVF International Conference on Computer Vision (ICCV), 2021, pp. 4015–4025.
- OpenAI, “GPT-4 Technical Report,” Mar. 2023, arXiv:2303.08774 [cs]. [Online]. Available: http://arxiv.org/abs/2303.08774
- J. L. Ba, J. R. Kiros, and G. E. Hinton, “Layer Normalization,” arXiv:1607.06450 [cs, stat], Jul. 2016, arXiv: 1607.06450.
- A. Vaswani, N. Shazeer, N. Parmar, J. Uszkoreit, L. Jones, A. N. Gomez, L. Kaiser, and I. Polosukhin, “Attention is All you Need,” in Advances in Neural Information Processing Systems, vol. 30. Curran Associates, Inc., 2017.
- B. Fischl and A. M. Dale, “Measuring the thickness of the human cerebral cortex from magnetic resonance images,” Proceedings of the National Academy of Sciences, vol. 97, no. 20, pp. 11 050–11 055, 2000.
- M. Hartig, D. Truran-Sacrey, S. Raptentsetsang, A. Simonson, A. Mezher, N. Schuff, M. Weiner et al., “Ucsf freesurfer methods,” ADNI Alzheimers Disease Neuroimaging Initiative: San Francisco, CA, USA, 2014.
- C. Bellenguez et al., “New insights into the genetic etiology of Alzheimer’s disease and related dementias,” Nature Genetics, vol. 54, no. 4, pp. 412–436, Apr. 2022, number: 4 Publisher: Nature Publishing Group.
- A. Buniello and J. MacArthur, “GWAS Catalog,” 2019, vol. 47 (Database issue): D1005-D1012.
- S. Purcell et al., “PLINK: a tool set for whole-genome association and population-based linkage analyses,” American Journal of Human Genetics, vol. 81, no. 3, pp. 559–575, Sep. 2007.
- F. Pedregosa and others, “Scikit-learn: Machine Learning in Python,” Journal of Machine Learning Research, vol. 12, pp. 2825–2830, 2011.
- D. J. Hand and R. J. Till, “A Simple Generalisation of the Area Under the ROC Curve for Multiple Class Classification Problems,” Machine Learning, vol. 45, no. 2, pp. 171–186, Nov. 2001.
- T. Zhou, K.-H. Thung, X. Zhu, and D. Shen, “Effective feature learning and fusion of multimodality data using stage-wise deep neural network for dementia diagnosis,” Human Brain Mapping, vol. 40, no. 3, pp. 1001–1016, Feb. 2019.
- Z. Gu and others, “circlize implements and enhances circular visualization in R,” Bioinformatics, vol. 30, no. 19, pp. 2811–2812, Oct. 2014.
- S. Terada et al., “Trail Making Test B and brain perfusion imaging in mild cognitive impairment and mild Alzheimer’s disease,” Psychiatry Research: Neuroimaging, vol. 213, no. 3, pp. 249–255, Sep. 2013.
- J. A. Matías-Guiu et al., “Neural Basis of Cognitive Assessment in Alzheimer Disease, Amnestic Mild Cognitive Impairment, and Subjective Memory Complaints,” The American Journal of Geriatric Psychiatry, vol. 25, no. 7, pp. 730–740, Jul. 2017.
- J. Camacho et al., “Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer’s disease,” Brain Pathology, vol. 32, no. 1, p. e13016, Sep. 2021.
- Google Bard. Alzheimer’s disease risk factors and their biological implications. [Online]. Available: https://bard.google.com
- M. Sundararajan, A. Taly, and Q. Yan, “Axiomatic Attribution for Deep Networks,” Jun. 2017, arXiv:1703.01365 [cs]. [Online]. Available: http://arxiv.org/abs/1703.01365
- L.-Y. Zhu, L. Shi, Y. Luo, J. Leung, and T. Kwok, “Brain MRI biomarkers to predict cognitive decline in older people with alzheimer’s disease,” vol. 88, no. 2, pp. 763–769, publisher: IOS Press. [Online]. Available: https://content.iospress.com/articles/journal-of-alzheimers-disease/jad215189
- C. Pettigrew, A. Soldan, Y. Zhu, M.-C. Wang, T. Brown, M. Miller, and M. Albert, “Cognitive reserve and cortical thickness in preclinical alzheimer’s disease,” vol. 11, no. 2, pp. 357–367. [Online]. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743433/
- L. Huang, W. Yu, W. Ma, W. Zhong, Z. Feng, H. Wang, Q. Chen, W. Peng, X. Feng, B. Qin, and T. Liu, “A survey on hallucination in large language models: Principles, taxonomy, challenges, and open questions.” [Online]. Available: http://arxiv.org/abs/2311.05232
- Diego Machado Reyes (2 papers)
- Hanqing Chao (18 papers)
- Juergen Hahn (4 papers)
- Li Shen (363 papers)
- Pingkun Yan (55 papers)