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Modelling Asthma Patients’ Responsiveness to Treatment Using Feature Selection and Evolutionary Computation

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Applications of Evolutionary Computation (EvoApplications 2021)

Abstract

For several medical treatments, it is possible to observe transcriptional variations in gene expressions between responders and non-responders. Modelling the correlation between such variations and the patient’s response to drugs as a system of Ordinary Differential Equations could be invaluable to improve the efficacy of treatments and would represent an important step towards personalized medicine. Two main obstacles lie on this path: (i) the number of genes is too large to straightforwardly analyze their interactions; (ii) defining the correct parameters for the mathematical models of gene interaction is a complex optimization problem, even when a limited number of genes is involved. In this paper, we propose a novel approach to creating mathematical models able to explain patients’ response to treatment from transcriptional variations. The approach is based on: (i) a feature selection algorithm, set to identify a minimal set of gene expressions that are highly correlated with treatment outcome, (ii) a state-of-the-art evolutionary optimizer, Covariance Matrix Adaptation Evolution Strategy, applied to finding the parameters of the mathematical model characterizing the relationship between gene expressions and patient responsiveness. The proposed methodology is tested on real-world data describing responsiveness of asthma patients to Omalizumab, a humanized monoclonal antibody that binds to immunoglobulin E. In this case study, the presented approach is shown able to identify 5 genes (out of 28,402) that are transcriptionally relevant to predict treatment outcomes, and to deliver a compact mathematical model that is able to explain the interaction between the different genes involved.

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Notes

  1. 1.

    https://github.com/steppenwolf0/modelingEvolutionaryComputation.

References

  1. Alrashoudi, R.H., Crane, I.J., Wilson, H.M., Al-Alwan, M., Alajez, N.M.: Gene expression data analysis identifies multiple deregulated pathways in patients with asthma. Biosci. Rep. 38(6), (2018)

    Google Scholar 

  2. Armstrong, C.G., Browne, G.J., Cohen, P., Cohen, P.T.: Ppp1r6, a novel member of the family of glycogen-targetting subunits of protein phosphatase 1. FEBS Lett. 418(1–2), 210–214 (1997)

    Article  Google Scholar 

  3. Banchereau, R., et al.: Personalized immunomonitoring uncovers molecular networks that stratify lupus patients. Cell 165(3), 551–565 (2016)

    Article  Google Scholar 

  4. Bigler, J., et al.: A severe asthma disease signature from gene expression profiling of peripheral blood from u-biopred cohorts. Am. J. Respir. Crit. Care Med. 195(10), 1311–1320 (2017)

    Article  Google Scholar 

  5. Bousquet, J., et al.: Predicting and evaluating response to omalizumab in patients with severe allergic asthma. Respir. Med. 101(7), 1483–1492 (2007)

    Article  Google Scholar 

  6. Chairakaki, A.D., et al.: Plasmacytoid dendritic cells drive acute asthma exacerbations. J. Allergy Clin. Immunol. 142(2), 542–556 (2018)

    Article  Google Scholar 

  7. Chaussabel, D., et al.: A modular analysis framework for blood genomics studies: application to systemic lupus erythematosus. Immunity 29(1), 150–164 (2008)

    Article  Google Scholar 

  8. Chien, Y., Fu, K.S.: On the generalized karhunen-loève expansion (corresp.). IEEE Trans. Inf. Theory 13(3), 518–520 (1967)

    Google Scholar 

  9. Dirami, T., et al.: Missense mutations in slc26a8, encoding a sperm-specific activator of CFTR, are associated with human asthenozoospermia. Am. J. Hum. Genetics 92(5), 760–766 (2013)

    Article  Google Scholar 

  10. Firat-Karalar, E.N., Sante, J., Elliott, S., Stearns, T.: Proteomic analysis of mammalian sperm cells identifies new components of the centrosome. J. Cell Sci. 127(19), 4128–4133 (2014)

    Article  Google Scholar 

  11. Gao, F., Han, L.: Implementing the nelder-mead simplex algorithm with adaptive parameters. Comput. Optim. Appl. 51(1), 259–277 (2012)

    Article  MathSciNet  Google Scholar 

  12. Guyon, I., Elisseeff, A.: An introduction to variable and feature selection. J. Mach. Learn. Res. 3, 1157–1182 (2003)

    MATH  Google Scholar 

  13. Guyon, I., Weston, J., Barnhill, S., Vapnik, V.: Gene selection for cancer classification using support vector machines. Machine learning 46(1–3), 389–422 (2002)

    Article  Google Scholar 

  14. Hamelmann, E.: The rationale for treating allergic asthma with anti-ige. Eur. Respir. Rev. 16(104), 61–66 (2007)

    Article  Google Scholar 

  15. Hansen, N., Ostermeier, A.: Completely derandomized self-adaptation in evolution strategies. Evol. Comput. 9(2), 159–195 (2001). https://doi.org/10.1063/1.2713540

    Article  Google Scholar 

  16. Huang, Y.C., Weng, C.M., Lee, M.J., Lin, S.M., Wang, C.H., Kuo, H.P.: Endotypes of severe allergic asthma patients who clinically benefit from anti-ige therapy. Clin. Exp. Allergy 49(1), 44–53 (2019)

    Article  Google Scholar 

  17. Humbert, M., et al.: Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (gina 2002 step 4 treatment): Innovate. Allergy 60(3), 309–316 (2005)

    Article  MathSciNet  Google Scholar 

  18. Lewis, P.: The characteristic selection problem in recognition systems. IRE Trans. Inform. Theory 8(2), 171–178 (1962)

    Article  Google Scholar 

  19. Lopez-Rincon, A., Martinez-Archundia, M., Martinez-Ruiz, G.U., Schoenhuth, A., Tonda, A.: Automatic discovery of 100-mirna signature for cancer classification using ensemble feature selection. BMC Bioinform. 20(1), 480 (2019)

    Article  Google Scholar 

  20. Lopez-Rincon, A., et al.: Machine learning-based ensemble recursive feature selection of circulating mirnas for cancer tumor classification. Cancers 12(7), 1785 (2020)

    Article  Google Scholar 

  21. Mandrekar, J.N.: Receiver operating characteristic curve in diagnostic test assessment. J. Thorac. Oncol. 5(9), 1315–1316 (2010)

    Article  Google Scholar 

  22. Murray, L., Xi, Y., Upham, J.W.: Clec4c gene expression can be used to quantify circulating plasmacytoid dendritic cells. J. Immunol. Methods 464, 126–130 (2019)

    Article  Google Scholar 

  23. Murray, L.M., Yerkovich, S.T., Ferreira, M.A., Upham, J.W.: Risks for cold frequency vary by sex: role of asthma, age, tlr7 and leukocyte subsets. Eur. Respir. J. (2020)

    Google Scholar 

  24. Pandey, G., et al.: A nasal brush-based classifier of asthma identified by machine learning analysis of nasal RNA sequence data. Sci. Rep. 8(1), 1–15 (2018)

    Google Scholar 

  25. Pedregosa, F., et al.: Scikit-learn: machine learning in python. J. Mach. Learn. Res. 12, 2825–2830 (2011)

    Google Scholar 

  26. Possa, S.S., Leick, E.A., Prado, C.M., Martins, M.A., Tibério, I.F.L.C.: Eosinophilic inflammation in allergic asthma. Front. Pharmacol. 4, 46 (2013)

    Article  Google Scholar 

  27. Šimundić, A.M.: Measures of diagnostic accuracy: basic definitions. Ejifcc 19(4), 203 (2009)

    Google Scholar 

  28. Thomas, B., et al.: Ciliary dysfunction and ultrastructural abnormalities are features of severe asthma. J. Allergy Clin. Immunol. 126(4), 722–729 (2010)

    Article  Google Scholar 

  29. Thomson, N.C., Chaudhuri, R.: Omalizumab: clinical use for the management of asthma. Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine 6, CCRPM-S7793 (2012)

    Google Scholar 

  30. Upchurch, K., et al.: Whole blood transcriptional variations between responders and non-responders in asthma patients receiving omalizumab. Clinical & Experimental Allergy (2020)

    Google Scholar 

  31. Vignolo, L.D., Milone, D.H., Scharcanski, J.: Feature selection for face recognition based on multi-objective evolutionary wrappers. Expert Syst. Appl. 40(13), 5077–5084 (2013)

    Article  Google Scholar 

  32. Virtanen, P., et al.: SciPy 1.0 Contributors: SciPy 1.0: fundamental algorithms for scientific computing in python. Nature Methods 17, 261–272 (2020). https://doi.org/10.1038/s41592-019-0686-2

  33. Vroman, H., Hendriks, R.W., Kool, M.: Dendritic cell subsets in asthma: impaired tolerance or exaggerated inflammation? Front. Immunol. 8, 941 (2017)

    Article  Google Scholar 

  34. Watson, C., et al.: Integrative transcriptomic analysis reveals key drivers of acute peanut allergic reactions. Nat. Commun. 8(1), 1–13 (2017)

    Article  MathSciNet  Google Scholar 

  35. Zhou, Z., Li, S., Qin, G., Folkert, M., Jiang, S., Wang, J.: Multi-objective based radiomic feature selection for lesion malignancy classification. IEEE J. Biomed. Health Inform. (2019)

    Google Scholar 

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Correspondence to Alejandro Lopez-Rincon .

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Lopez-Rincon, A. et al. (2021). Modelling Asthma Patients’ Responsiveness to Treatment Using Feature Selection and Evolutionary Computation. In: Castillo, P.A., Jiménez Laredo, J.L. (eds) Applications of Evolutionary Computation. EvoApplications 2021. Lecture Notes in Computer Science(), vol 12694. Springer, Cham. https://doi.org/10.1007/978-3-030-72699-7_23

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  • DOI: https://doi.org/10.1007/978-3-030-72699-7_23

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