IDEAS home Printed from https://ideas.repec.org/a/spr/compst/v32y2017i2d10.1007_s00180-016-0707-x.html
   My bibliography  Save this article

Unsupervised learning of pharmacokinetic responses

Author

Listed:
  • Elson Tomás

    (Universidade de Lisboa)

  • Susana Vinga

    (Universidade de Lisboa)

  • Alexandra M. Carvalho

    (Universidade de Lisboa)

Abstract

Pharmacokinetics (PK) is a branch of pharmacology dedicated to the study of the time course of drug concentrations, from absorption to excretion from the body. PK dynamic models are often based on homogeneous, multi-compartment assumptions, which allow to identify the PK parameters and further predict the time evolution of drug concentration for a given subject. One key characteristic of these time series is their high variability among patients, which may hamper their correct stratification. In the present work, we address this variability by estimating the PK parameters and simultaneously clustering the corresponding subjects using the time series. We propose an expectation maximization algorithm that clusters subjects based on their PK drug responses, in an unsupervised way, collapsing clusters that are closer than a given threshold. Experimental results show that the proposed algorithm converges fast and leads to meaningful results in synthetic and real scenarios.

Suggested Citation

  • Elson Tomás & Susana Vinga & Alexandra M. Carvalho, 2017. "Unsupervised learning of pharmacokinetic responses," Computational Statistics, Springer, vol. 32(2), pages 409-428, June.
    • Handle: RePEc:spr:compst:v:32:y:2017:i:2:d:10.1007_s00180-016-0707-x
    DOI: 10.1007/s00180-016-0707-x
    as

    Download full text from publisher

    File URL: http://link.springer.com/10.1007/s00180-016-0707-x
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1007/s00180-016-0707-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    References listed on IDEAS

    as
    1. NESTEROV, Yurii, 2012. "Efficiency of coordinate descent methods on huge-scale optimization problems," LIDAM Reprints CORE 2511, Université catholique de Louvain, Center for Operations Research and Econometrics (CORE).
    2. Laura Azzimonti & Francesca Ieva & Anna Maria Paganoni, 2013. "Nonlinear nonparametric mixed-effects models for unsupervised classification," Computational Statistics, Springer, vol. 28(4), pages 1549-1570, August.
    3. Lang Wu, 2004. "Exact and Approximate Inferences for Nonlinear Mixed-Effects Models With Missing Covariates," Journal of the American Statistical Association, American Statistical Association, vol. 99, pages 700-709, January.
    4. Kuhn, E. & Lavielle, M., 2005. "Maximum likelihood estimation in nonlinear mixed effects models," Computational Statistics & Data Analysis, Elsevier, vol. 49(4), pages 1020-1038, June.
    5. Wu L., 2002. "A Joint Model for Nonlinear Mixed-Effects Models With Censoring and Covariates Measured With Error, With Application to AIDS Studies," Journal of the American Statistical Association, American Statistical Association, vol. 97, pages 955-964, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Samson, Adeline & Lavielle, Marc & Mentre, France, 2006. "Extension of the SAEM algorithm to left-censored data in nonlinear mixed-effects model: Application to HIV dynamics model," Computational Statistics & Data Analysis, Elsevier, vol. 51(3), pages 1562-1574, December.
    2. Marc Lavielle & Adeline Samson & Ana Karina Fermin & France Mentré, 2011. "Maximum Likelihood Estimation of Long-Term HIV Dynamic Models and Antiviral Response," Biometrics, The International Biometric Society, vol. 67(1), pages 250-259, March.
    3. Christian E. Galarza & Luis M. Castro & Francisco Louzada & Victor H. Lachos, 2020. "Quantile regression for nonlinear mixed effects models: a likelihood based perspective," Statistical Papers, Springer, vol. 61(3), pages 1281-1307, June.
    4. Fu, Liyong & Wang, Mingliang & Lei, Yuancai & Tang, Shouzheng, 2014. "Parameter estimation of two-level nonlinear mixed effects models using first order conditional linearization and the EM algorithm," Computational Statistics & Data Analysis, Elsevier, vol. 69(C), pages 173-183.
    5. Wei Liu & Lang Wu, 2007. "Simultaneous Inference for Semiparametric Nonlinear Mixed-Effects Models with Covariate Measurement Errors and Missing Responses," Biometrics, The International Biometric Society, vol. 63(2), pages 342-350, June.
    6. Getachew A. Dagne, 2016. "A growth mixture Tobit model: application to AIDS studies," Journal of Applied Statistics, Taylor & Francis Journals, vol. 43(7), pages 1174-1185, July.
    7. Lu Tang & Ling Zhou & Peter X. K. Song, 2019. "Fusion learning algorithm to combine partially heterogeneous Cox models," Computational Statistics, Springer, vol. 34(1), pages 395-414, March.
    8. Yuzhu Tian & Er’qian Li & Maozai Tian, 2016. "Bayesian joint quantile regression for mixed effects models with censoring and errors in covariates," Computational Statistics, Springer, vol. 31(3), pages 1031-1057, September.
    9. Francesco BARTOLUCCI & Silvia BACCI & Claudia PIGINI, 2015. "A Misspecification Test for Finite-Mixture Logistic Models for Clustered Binary and Ordered Responses," Working Papers 410, Universita' Politecnica delle Marche (I), Dipartimento di Scienze Economiche e Sociali.
    10. Wei Liu & Shuyou Li, 2015. "A multiple imputation approach to nonlinear mixed-effects models with covariate measurement errors and missing values," Journal of Applied Statistics, Taylor & Francis Journals, vol. 42(3), pages 463-476, March.
    11. Xuefei Lu & Alessandro Rudi & Emanuele Borgonovo & Lorenzo Rosasco, 2020. "Faster Kriging: Facing High-Dimensional Simulators," Operations Research, INFORMS, vol. 68(1), pages 233-249, January.
    12. TAYLOR, Adrien B. & HENDRICKX, Julien M. & François GLINEUR, 2016. "Exact worst-case performance of first-order methods for composite convex optimization," LIDAM Discussion Papers CORE 2016052, Université catholique de Louvain, Center for Operations Research and Econometrics (CORE).
    13. Ibirénoyé Romaric Sodjahin & Fabienne Femenia & Obafemi Philippe Koutchade & A. Carpentier, 2022. "On the economic value of the agronomic effects of crop diversification for farmers: estimation based on farm cost accounting data [Valeur économique des effets agronomiques de la diversification de," Working Papers hal-03639951, HAL.
    14. Wang, Xiaoning & Schumitzky, Alan & D'Argenio, David Z., 2007. "Nonlinear random effects mixture models: Maximum likelihood estimation via the EM algorithm," Computational Statistics & Data Analysis, Elsevier, vol. 51(12), pages 6614-6623, August.
    15. Liang, Hua & Su, Haiyan & Zou, Guohua, 2008. "Confidence intervals for a common mean with missing data with applications in an AIDS study," Computational Statistics & Data Analysis, Elsevier, vol. 53(2), pages 546-553, December.
    16. Andrej Čopar & Blaž Zupan & Marinka Zitnik, 2019. "Fast optimization of non-negative matrix tri-factorization," PLOS ONE, Public Library of Science, vol. 14(6), pages 1-15, June.
    17. Zhang, Yuexia & Qin, Guoyou & Zhu, Zhongyi & Zhang, Jiajia, 2018. "Robust estimation in linear regression models for longitudinal data with covariate measurement errors and outliers," Journal of Multivariate Analysis, Elsevier, vol. 168(C), pages 261-275.
    18. Duy Khuong Nguyen & Tu Bao Ho, 2017. "Accelerated parallel and distributed algorithm using limited internal memory for nonnegative matrix factorization," Journal of Global Optimization, Springer, vol. 68(2), pages 307-328, June.
    19. Lu, Xiaosun & Huang, Yangxin & Zhu, Yiliang, 2016. "Finite mixture of nonlinear mixed-effects joint models in the presence of missing and mismeasured covariate, with application to AIDS studies," Computational Statistics & Data Analysis, Elsevier, vol. 93(C), pages 119-130.
    20. Abbaszadehpeivasti, Hadi & de Klerk, Etienne & Zamani, Moslem, 2023. "Convergence rate analysis of randomized and cyclic coordinate descent for convex optimization through semidefinite programming," Other publications TiSEM 88512ac0-c26a-4a99-b840-3, Tilburg University, School of Economics and Management.

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:spr:compst:v:32:y:2017:i:2:d:10.1007_s00180-016-0707-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.springer.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.