Artificial intelligence for precision oncology: beyond patient stratification

Francisco Azuaje, Francisco Azuaje

Abstract

The data-driven identification of disease states and treatment options is a crucial challenge for precision oncology. Artificial intelligence (AI) offers unique opportunities for enhancing such predictive capabilities in the lab and the clinic. AI, including its best-known branch of research, machine learning, has significant potential to enable precision oncology well beyond relatively well-known pattern recognition applications, such as the supervised classification of single-source omics or imaging datasets. This perspective highlights key advances and challenges in that direction. Furthermore, it argues that AI's scope and depth of research need to be expanded to achieve ground-breaking progress in precision oncology.

Conflict of interest statement

The author declares no competing interests.

Figures

Fig. 1
Fig. 1
AI in precision oncology: beyond patient stratification. Selection of key advances and challenges, as well as long-term outlook, discussed in this perspective. Associations between future outlook and challenges are indicated with arrows connecting the former to the latter

References

    1. Turing AM. Computing machinery and intelligence. Mind. 1950;49:433–460. doi: 10.1093/mind/LIX.236.433.
    1. Jordan MI, Mitchell TM. Machine learning: trends, perspectives, and prospects. Science. 2015;349:255–260. doi: 10.1126/science.aaa8415.
    1. Mitchell, T. M. Machine Learning (McGraw-Hill Science/Engineering/Math, Boston, Mass, USA, 1997).
    1. Peek N, Combi C, Marin R, Bellazzi R. Thirty years of artificial intelligence in medicine (AIME) conferences: a review of research themes. Artif. Intell. Med. 2015;65:61–73. doi: 10.1016/j.artmed.2015.07.003.
    1. Yu KH, Beam AL, Kohane IS. Artificial intelligence in healthcare. Nat. Biomed. Eng. 2018;2:719–731. doi: 10.1038/s41551-018-0305-z.
    1. Lynch CJ, Liston C. New machine-learning technologies for computer-aided diagnosis. Nat. Med. 2018;24:1304–1305. doi: 10.1038/s41591-018-0178-4.
    1. Wong D, Yip S. Machine learning classifies cancer. Nature. 2018;555:446–447. doi: 10.1038/d41586-018-02881-7.
    1. Zhang W, Chien J, Yong J, Kuang R. Network-based machine learning and graph theory algorithms for precision oncology. npj Precis. Oncol. 2017;1:25. doi: 10.1038/s41698-017-0029-7.
    1. Ching, T. et al. Opportunities and obstacles for deep learning in biology and medicine. J. R. Soc. Interface15, 20170387 (2018).
    1. Richter AN, Khoshgoftaar TM. A review of statistical and machine learning methods for modeling cancer risk using structured clinical data. Artif. Intell. Med. 2018;90:1–14. doi: 10.1016/j.artmed.2018.06.002.
    1. Esteva A, et al. Dermatologist-level classification of skin cancer with deep neural networks. Nature. 2017;542:115–118. doi: 10.1038/nature21056.
    1. LeCun Y, Bengio Y, Hinton G. Deep learning. Nature. 2015;521:436–444. doi: 10.1038/nature14539.
    1. Goodfellow, I., Bengio, Y. & Courville, A. Deep Learning (MIT Press, Cambridge, Mass, USA, 2016).
    1. Coudray N, et al. Classification and mutation prediction from non-small cell lung cancer histopathology images using deep learning. Nat. Med. 2018;24:1559–1567. doi: 10.1038/s41591-018-0177-5.
    1. Ehteshami Bejnordi B, et al. Diagnostic assessment of deep learning algorithms for detection of lymph node metastases in women with breast cancer. JAMA. 2017;318:2199–2210. doi: 10.1001/jama.2017.14585.
    1. Rawat W, Wang Z. Deep convolutional neural networks for image classification: a comprehensive review. Neural Comput. 2017;29:2352–2449. doi: 10.1162/neco_a_00990.
    1. Bailey MH, et al. Comprehensive characterization of cancer driver genes and mutations. Cell. 2018;173:371–385. doi: 10.1016/j.cell.2018.02.060.
    1. Ghahramani Z. Probabilistic machine learning and artificial intelligence. Nature. 2015;521:452–459. doi: 10.1038/nature14541.
    1. Touw WG, et al. Data mining in the Life Sciences with Random Forest: a walk in the park or lost in the jungle? Brief. Bioinform. 2013;14:315–326. doi: 10.1093/bib/bbs034.
    1. Azuaje F. Computational models for predicting drug responses in cancer research. Brief. Bioinform. 2017;18:820–829.
    1. Zhao, L., Lee, V. H. F., Ng, M. K., Yan, H. & Bijlsma, M. F. Molecular subtyping of cancer: current status and moving toward clinical applications. Brief. Bioinform.10.1093/bib/bby026 (2018).
    1. Karczewski KJ, Snyder MP. Integrative omics for health and disease. Nat. Rev. Genet. 2018;19:229–310. doi: 10.1038/nrg.2018.4.
    1. Li Y, Wu FX, Ngom A. A review on machine learning principles for multi-view biological data integration. Brief. Bioinform. 2018;19:325–340.
    1. Ramazzotti, D., Lal, A., Wang, B., Batzoglou, S. & Sidow, A. Multi-omic tumor data reveal diversity of molecular mechanisms that correlate with survival. Preprint at (2018).
    1. Kim D, et al. Knowledge boosting: a graph-based integration approach with multi-omics data and genomic knowledge for cancer clinical outcome prediction. J. Am. Med. Inform. Assoc. 2015;22:109–120. doi: 10.1093/jamia/ocv014.
    1. Klughammer J, et al. The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space. Nat. Med. 2018;24:1611–1624. doi: 10.1038/s41591-018-0156-x.
    1. Yu KH, et al. Association of omics features with histopathology patterns in lung adenocarcinoma. Cell Syst. 2017;5:620–627. doi: 10.1016/j.cels.2017.10.014.
    1. Gevaert O, et al. Glioblastoma multiforme: exploratory radiogenomic analysis by using quantitative image features. Radiology. 2014;273:168–174. doi: 10.1148/radiol.14131731.
    1. Disselhorst JA, et al. Linking imaging to omics utilizing image-guided tissue extraction. Proc. Natl. Acad. Sci. U.S.A. 2018;115:E2980–E2987. doi: 10.1073/pnas.1718304115.
    1. Pan SJ, Yang Q. A survey on transfer learning. IEEE Trans. Knowl. Data Eng. 2010;22:1345–1359. doi: 10.1109/TKDE.2009.191.
    1. Szegedy, C., Vanhoucke, V., Ioffe, S., Shlens, J. & Wojna, Z. Rethinking the inception architecture for computer vision. Preprint at (2015).
    1. Sevakula, R. K., Singh, V., Verma, N. K., Kumar, C. & Cui, Y. Transfer learning for molecular cancer classification using deep neural networks. IEEE/ACM Trans. Comput. Biol. Bioinform.10.1109/TCBB.2018.2822803 (2018).
    1. Turki TW, Wei Z, Wang JTL. Transfer learning approaches to improve drug sensitivity prediction in multiple myeloma patients. IEEE Access. 2017;5:7381–7393. doi: 10.1109/ACCESS.2017.2696523.
    1. Tan M. Prediction of anti-cancer drug response by kernelized multi-task learning. Artif. Intell. Med. 2016;73:70–77. doi: 10.1016/j.artmed.2016.09.004.
    1. Shaikhina T, Khovanova NA. Handling limited datasets with neural networks in medical applications: a small-data approach. Artif. Intell. Med. 2017;75:51–63. doi: 10.1016/j.artmed.2016.12.003.
    1. Choi, C. et al. RETAIN: an interpretable predictive model for healthcare using reverse time attention mechanism. Preprint at (2016).
    1. Lahav, O., Mastronarde, N. & van der Schaar, M. What is interpretable? Using machine learning to design interpretable decision-support systems. Preprint at (2018).
    1. Alaa, A. M. & van der Schaar, M. Forecasting individualized disease trajectories using interpretable deep learning. Preprint at (2018).
    1. Castelvecchi D. Can we open the black box of AI? Nature. 2016;538:20–23. doi: 10.1038/538020a.
    1. Lundberg SM, et al. Explainable machine-learning predictions for the prevention of hypoxaemia during surgery. Nat. Biomed. Eng. 2018;2:749–760. doi: 10.1038/s41551-018-0304-0.
    1. Li, O., Liu, H., Chen, C. & Rudin, C. Deep learning for case-based reasoning through prototypes: a neural network that explains its predictions. Preprint at (2017).
    1. Chen, C., Li, O., Barnett, A., Su, J. & Rudin, C. This looks like that: deep learning for interpretable image recognition. Preprint at (2018).
    1. Ancona, M., Ceolini, E., Öztireli, C. & Gross, M. Towards better understanding of gradient-based attribution methods for deep neural networks. Preprint at (2018).
    1. Fabris F, Doherty A, Palmer D, de Magalhaes JP, Freitas AA. A new approach for interpreting Random Forest models and its application to the biology of ageing. Bioinformatics. 2018;34:2449–2456. doi: 10.1093/bioinformatics/bty087.
    1. Basu S, Kumbier K, Brown JB, Yu B. Iterative random forests to discover predictive and stable high-order interactions. Proc. Natl. Acad. Sci. U.S.A. 2018;115:1943–1948. doi: 10.1073/pnas.1711236115.
    1. Yu MK, et al. Visible machine learning for biomedicine. Cell. 2018;173:1562–1565. doi: 10.1016/j.cell.2018.05.056.
    1. Yauney G, Shah P. Reinforcement learning with action-derived rewards for chemotherapy and clinical trial dosing regimen selection. Proc. Mach. Learn. Res. 2018;85:161–226.
    1. Ali I, et al. Lung nodule detection via deep reinforcement learning. Front. Oncol. 2018;8:108. doi: 10.3389/fonc.2018.00108.
    1. Padmanabhan R, Meskin N, Haddad WM. Reinforcement learning-based control of drug dosing for cancer chemotherapy treatment. Math. Biosci. 2017;293:11–20. doi: 10.1016/j.mbs.2017.08.004.
    1. Tseng HH, et al. Deep reinforcement learning for automated radiation adaptation in lung cancer. Med. Phys. 2017;44:6690–6705. doi: 10.1002/mp.12625.
    1. Mahmud M, Kaiser MS, Hussain A, Vassanelli S. Applications of deep learning and reinforcement learning to biological data. IEEE Trans. Neural Netw. Learn. Syst. 2018;29:2063–2079. doi: 10.1109/TNNLS.2018.2790388.
    1. Girardi D, et al. Interactive knowledge discovery with the doctor-in-the-loop: a practical example of cerebral aneurysms research. Brain Inform. 2016;3:133–143. doi: 10.1007/s40708-016-0038-2.
    1. Pearl, J. Causality: Models, Reasoning and Inference (Cambridge University Press, Cambridge, England, 2000).
    1. Yoon, J., Jordon, J. & Van der Schaar, M. GANITE: estimation of individualized treatment effects using generative adversarial nets. In International Conference on Learning Representations. (2018).
    1. Alaa, A. M. & Van der Schaar, M. AutoPrognosis: automated clinical prognostic modeling via Bayesian optimization with structured Kernel learning. Preprint at (2018).

Source: PubMed

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