Predicting Drug Response with Multi-Task Gradient-Boosted Trees in Epilepsy

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Abstract Motivation Despite the availability of numerous anti-seizure medications (ASMs), drug resistance remains a major issue for people with epilepsy. The probability of achieving seizure freedom diminishes with each unsuccessful drug trial, and the impact of genetic and clinical markers on ASM response remains unclear. To address this issue, we used state-of-the-art machine learning (ML) methods to predict the response of people with epilepsy to individual ASMs based on their clinical and genomic information. Results To overcome data sparsity for less common drugs, we implement a multi-task (MT) learning approach for gradient-boosted trees (GBTs), assuming that predicting responses to different ASMs involves similar tasks. This strategy allows models for less prevalent drugs to leverage the more abundant data available for other drugs during training. The proposed model outperforms individual and combined drug-response predictions for most drugs. Our findings identify key genomic and clinical features influencing drug response, enhancing understanding of individual drug responses in people with epilepsy, and aiding clinicians in making informed treatment decisions. Availability and Implementation Due to privacy reasons data is not publically available. The code will be made available upon acceptance under https://github.com/pfeiferAI/MT-GBT

Authors 17

1. Christian M. Boßelmann

   University of Tübingen · Hertie Institute for Clinical Brain Research

   Affiliation as printed

   Department of Neurology and Epileptology , Hertie Institute for Clinical Brain Research , University of Tübingen , Tübingen , Germany,

   University of Tuebingen

2. Roland Krause

   Luxembourg Centre for Systems Biomedicine

   Affiliation as printed

   Bioinformatics core, Luxembourg Centre for Systems Biomedicine (LCSB);

   Bioinformatics core, Luxembourg Centre for Systems Biomedicine (LCSB)

3. Patrick May

   University of Luxembourg

   Affiliation as printed

   University of Luxembourg;

   University of Luxembourg

4. Stefan Wolking Aachen

   Universitätsklinikum Aachen

   Affiliation as printed

   RTWH Uniklinik Aachen;

   RTWH Uniklinik Aachen

5. Gianpiero L. Cavalleri

   Royal College of Surgeons in Ireland

   Affiliation as printed

   Royal College of Surgeons in Ireland, Dublin;

   Royal College of Surgeons in Ireland, Dublin

6. Norman Delanty

   Royal College of Surgeons in Ireland

   Affiliation as printed

   Royal College of Surgeons in Ireland;

   Royal College of Surgeons in Ireland

7. John J. Craig

   Belfast Health and Social Care Trust · Royal Victoria Hospital

   Affiliation as printed

   Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast;

   Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast

8. Chantal Depondt
   Affiliation as printed

   Hopital Universitaire de Bruxelles, Brussels;

   Hopital Universitaire de Bruxelles, Brussels

9. Bobby P. C. Koeleman

   University Medical Center Utrecht

   Affiliation as printed

   University Medical Center Utrecht, Utrecht;

   University Medical Center Utrecht, Utrecht

10. Anthony Guy Marson

    University of Liverpool

    Affiliation as printed

    University of Liverpool;

    University of Liverpool

11. Terence John O'Brien

    Monash University · The Alfred Hospital

    Affiliation as printed

    The Alfred Hospital, Monash University, Melbourne

12. Josemir W. A. S. Sander

    University College London · UCL Queen Square Institute of Neurology

    Affiliation as printed

    UCL Queen Square Institute of Neurology, London WC1N 3BG & Chalfont Centre for Epilepsy, Chalfont St Peter SL9 ORJ, United Kingdom;

    UCL Queen Square Institute of Neurology, London WC1N 3BG & Chalfont Centre for Epilepsy, Chalfont St Peter SL9 ORJ, United Kingdom

13. Graeme John Sills

    University of Glasgow

    Affiliation as printed

    University of Glasgow;

    University of Glasgow

14. Federico Zara

    University of Genoa

    Affiliation as printed

    Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova;

    Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova

15. Hreinn Stefánsson

    deCODE Genetics (Iceland)

    Affiliation as printed

    deCODE Genetics, Reykjavik;

    deCODE genetics

16. Holger Lerche

    University of Tübingen · Universitätsklinikum Tübingen

    Affiliation as printed

    Universitaetsklinikum Tuebingen;

    University of Tübingen: Eberhard Karls Universitat Tubingen

17. Nico Pfeifer

    University of Tübingen

    Affiliation as printed

    University of Tübingen: Eberhard Karls Universitat Tubingen