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A Multi-Modular System-Genetics (MMSG) Approach for Deep Representation Learning for Personalized Treatment of Cancer Using Sensitivity Analysis of Precision Drugs and Gene Expression Data

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Data-Enabled Discovery and Applications

Abstract

One-size-fits-all has never succeeded profoundly and this is the reason why personalization has become so important. Many fatal diseases face such problem due to intense and risky medication procedures with immense side effects. Personalized medication through precision medicine is the new big thing that will provide better treatment solution through analysis and artificial intelligence. In this work, we have introduced for the first time a multi-modular training approach (MMSG+DRRL/ERRL) for generalized representation for cancer drug prediction based on gene expression for personalized treatment through the use of different system-genetics information like subclinical medical information to determine their suitability. We have shown how different modular information can be used computationally to enhance prediction behavior using the genetic and subcategory information of cancer diseases. Subcategorization analysis can decode many useful information of the disease and can help in better treatment modeling. We have shown for the first time how we can use the subcategory information to extract sensitivity of cancer cell lines for different drugs, a procedure never tried before. We have utilized the best practices of the feature training for deep learning to determine the interacting genes for particular drugs.

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References

  1. J. Baselga, et al., Phase I safety, pharmacokinetics, and inhibition of SRC activity study of saracatinib in patients with solid tumors. Clin. Cancer Res. 16.19, 4876–4883 (2010)

    Article  Google Scholar 

  2. N. Berlow, et al., A new approach for prediction of tumor sensitivity to targeted drugs based on functional data. BMC Bioinform. 14.1, 239 (2013)

    Article  Google Scholar 

  3. A.A. Borisy, et al., Systematic discovery of multicomponent therapeutics. Proc. Natl. Acad. Sci. 100.13, 7977–7982 (2003)

    Article  Google Scholar 

  4. I.I.I. Burris, A. Howard, et al., Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas. J. Clin. Oncol. 23.23, 5305–5313 (2005)

    Article  Google Scholar 

  5. G. Caponigro, W.R. Sellers, Advances in the preclinical testing of cancer therapeutic hypotheses. Nature reviews. Drug Discovery. 10.3, 179 (2011)

    Article  Google Scholar 

  6. J. Barretina, et al., The cancer cell line encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 483.7391, 603–607 (2012)

    Article  Google Scholar 

  7. A.L. Cohen, et al., A pharmacogenomic method for individualized prediction of drug sensitivity. Mol. Syst. Biol. 7.1, 513 (2011)

    Article  Google Scholar 

  8. J.C. Costello, et al., A community effort to assess and improve drug sensitivity prediction algorithms. Nature Biotechnol. 32.12, 1202–1212 (2014)

    Article  Google Scholar 

  9. Y. Deng, et al., The concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung cancer. Mol. Clin. Oncol. 2.1, 116–120 (2014)

    Article  Google Scholar 

  10. H.B. Frieboes, et al., Prediction of drug response in breast cancer using integrative experimental/computational modeling. Cancer Res. 69.10, 4484–4492 (2009)

    Article  Google Scholar 

  11. M.J. Garnett, et al., Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature. 483.7391, 570–575 (2012)

    Article  Google Scholar 

  12. W. Yang, et al., Genomics of drug sensitivity in cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells. Nucleic Acids Res. 41.D1, D955–D961 (2012)

    Article  Google Scholar 

  13. M.C. Garassino, et al., Different types of K-Ras mutations could affect drug sensitivity and tumour behaviour in non-small-cell lung cancer. Ann. Oncol. 22.1, 235–237 (2011)

    Article  Google Scholar 

  14. L.A. Garraway, et al., Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature. 436.7047, 117 (2005)

    Article  Google Scholar 

  15. J. Greshock, et al., Molecular target class is predictive of in vitro response profile. Cancer Res. 70.9, 3677–3686 (2010)

    Article  Google Scholar 

  16. B. Seashore-Ludlow, et al., Harnessing connectivity in a large-scale small-molecule sensitivity dataset. Cancer Discovery. 5.11, 1210–1223 (2015)

    Article  Google Scholar 

  17. A. Holleman, et al., Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment. New England J. Med. 351.6, 533–542 (2004)

    Article  Google Scholar 

  18. E.B. Haura, et al., A phase II study of PD-0325901, an oral MEK inhibitor, in previously treated patients with advanced non–small cell lung cancer. Clin. Cancer Res. 16.8, 2450–2457 (2010)

    Article  Google Scholar 

  19. J.K. Lee, et al., A strategy for predicting the chemosensitivity of human cancers and its application to drug discovery. Proc. Natl. Acad. Sci. 104.32, 13086–13091 (2007)

    Article  Google Scholar 

  20. W.M. Lin, et al., Modeling genomic diversity and tumor dependency in malignant melanoma. Cancer Res. 68.3, 664–673 (2008)

    Article  Google Scholar 

  21. U. McDermott, et al., Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling. Proc. Natl. Acad. Sci. 104.50, 19936–19941 (2007)

    Article  Google Scholar 

  22. L.E. MacConaill, L.A. Garraway, Clinical implications of the cancer genome. J. Clin. Oncol. 28.35, 5219–5228 (2010)

    Article  Google Scholar 

  23. R.M. Neve, et al., A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. 10.6, 515–527 (2006)

    Article  Google Scholar 

  24. H. Park, et al., Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker. PloS one. 9.10, e108990 (2014)

    Article  Google Scholar 

  25. Y. Qin, et al., A network flow-based method to predict anticancer drug sensitivity. PloS one. 10.5, e0127380 (2015)

    Article  Google Scholar 

  26. G. Riddick, et al., Predicting in vitro drug sensitivity using random forests. Bioinformatics27. 2, 220–224 (2010)

    Google Scholar 

  27. D.T. Ross, et al., Systematic variation in gene expression patterns in human cancer cell lines. Nature Genetics. 24.3, 227 (2000)

    Article  Google Scholar 

  28. C. Sawyers, Targeted cancer therapy. Nature. 432.7015, 294 (2004)

    Article  Google Scholar 

  29. L. Shen, et al., Drug sensitivity prediction by CpG island methylation profile in the NCI-60 cancer cell line panel. Cancer Res. 67.23, 11335–11343 (2007)

    Article  Google Scholar 

  30. D.B. Solit, et al., BRAF Mutation predicts sensitivity to MEK inhibition. Nature. 439.7074, 358–362 (2006)

    Article  Google Scholar 

  31. M.R. Stratton, P.J. Campbell, P. Andrew Futreal, The cancer genome. Nature. 458.7239, 719–724 (2009)

    Article  Google Scholar 

  32. J.E. Staunton, et al., Chemosensitivity prediction by transcriptional profiling. Proc. Natl. Acad. Sci. 98.19, 10787–10792 (2001)

    Article  Google Scholar 

  33. W.R. Sellers, D.E. Fisher, Apoptosis and cancer drug targeting. J. Clin. Investig. 104.12, 1655 (1999)

    Article  Google Scholar 

  34. M.L. Sos, et al., Predicting drug susceptibility of non–small cell lung cancers based on genetic lesions. J. Clin. Investig. 6(2009), 119 (1727)

    Google Scholar 

  35. H. Tang, et al., A 12-gene set predicts survival benefits from adjuvant chemotherapy in non–small cell lung cancer patients. Clin. Cancer Res. 19.6, 1577–1586 (2013)

    Article  Google Scholar 

  36. R.K. Thomas, et al., High-throughput oncogene mutation profiling in human cancer. Nature Genetics. 39.3, 347 (2007)

    Article  Google Scholar 

  37. A. Urruticoechea, et al., Recent advances in cancer therapy: an overview. Curr. Pharm. Des. 16.1, 3–10 (2010)

    Article  Google Scholar 

  38. T. Wada, J.M. Penninger, Mitogen-activated protein kinases in apoptosis regulation. Oncogene. 23.16, 2838–2849 (2004)

    Article  Google Scholar 

  39. J.N. Weinstein, et al., An information-intensive approach to the molecular pharmacology of cancer. Science. 275.5298, 343–349 (1997)

    Article  Google Scholar 

  40. X.-M. Zhao, et al., Prediction of drug combinations by integrating molecular and pharmacological data. PLoS Comput. Biol. 7.12, e1002323 (2011)

    Article  Google Scholar 

  41. N. Zhang, et al., Predicting anticancer drug responses using a dual-layer integrated cell line-drug network model. PLoS Comput. Biol. 11.9, e1004498 (2015)

    Article  Google Scholar 

  42. S. Kim, et al., Integrating domain specific knowledge and network analysis to predict drug sensitivity of cancer cell lines. PloS one. 11.9, e0162173 (2016)

    Article  Google Scholar 

  43. F.A. Gers, J. Schmidhuber, F. Cummins, Learning to forget: Continual prediction with LSTM, pp. 850–855 (1999)

  44. J. Chung, et al., Empirical evaluation of gated recurrent neural networks on sequence modeling. arXiv:1412.3555 (2014)

  45. S.B. Gelfand, C.S. Ravishankar, E.J. Delp, in An iterative growing and pruning algorithm for classification tree design. IEEE International Conference on Systems, Man and Cybernetics, 1989. Conference Proceedings (IEEE, 1989)

  46. Y. Bengio, A. Courville, P. Vincent, Representation learning: a review and new perspectives. IEEE Trans. Pattern Anal. Mach. Intell. 35.8, 1798–1828 (2013)

    Article  Google Scholar 

  47. H. Zou, T. Hastie, Regularization and variable selection via the elastic net. Journal of the Royal Statistical Society: Series B (Statistical Methodology). 67.2, 301–320 (2005)

    Article  MathSciNet  MATH  Google Scholar 

  48. G.E. Hinton, A. Krizhevsky, S.D. Wang, in Transforming auto-encoders. International Conference on Artificial Neural Networks (Springer, Berlin, 2011)

  49. K.P. Murphy, Naive bayes classifiers. University of British Columbia (2006)

  50. S. Menard, Applied logistic regression analysis. Vol. 106 Sage (2002)

  51. A. Liaw, M. Wiener, Classification and regression by randomForest. R news. 2.3, 18–22 (2002)

    Google Scholar 

  52. Johan AK Suykens, J. Vandewalle, Least squares support vector machine classifiers. Neural Process. Lett. 9.3, 293–300 (1999)

    Article  Google Scholar 

  53. R. Rahman, et al., Heterogeneity aware random forest for drug sensitivity prediction. Sci. Rep. 7.1, 11347 (2017)

    Article  Google Scholar 

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Correspondence to Chiranjib Sur.

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Sur, C. A Multi-Modular System-Genetics (MMSG) Approach for Deep Representation Learning for Personalized Treatment of Cancer Using Sensitivity Analysis of Precision Drugs and Gene Expression Data. Data-Enabled Discov. Appl. 3, 11 (2019). https://doi.org/10.1007/s41688-019-0035-8

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