A Machine Learning Approach for High-Dimensional Time-to-Event Prediction With Application to Immunogenicity of Biotherapies in the ABIRISK Cohort.

Journal: Frontiers in immunology
PMID:

Abstract

Predicting immunogenicity for biotherapies using patient and drug-related factors represents nowadays a challenging issue. With the growing ability to collect massive amount of data, machine learning algorithms can provide efficient predictive tools. From the bio-clinical data collected in the multi-cohort of autoimmune diseases treated with biotherapies from the ABIRISK consortium, we evaluated the predictive power of a custom-built random survival forest for predicting the occurrence of anti-drug antibodies. This procedure takes into account the existence of a population composed of immune-reactive and immune-tolerant subjects as well as the existence of a tiny expected proportion of relevant predictive variables. The practical application to the ABIRISK cohort shows that this approach provides a good predictive accuracy that outperforms the classical survival random forest procedure. Moreover, the individual predicted probabilities allow to separate high and low risk group of patients. To our best knowledge, this is the first study to evaluate the use of machine learning procedures to predict biotherapy immunogenicity based on bioclinical information. It seems that such approach may have potential to provide useful information for the clinical practice of stratifying patients before receiving a biotherapy.

Authors

  • Julianne Duhazé
    Research Center, Ste-Justine Hospital, Montreal, QC, Canada.
  • Signe Hässler
    UMR 1018, INSERM, CESP, Paris-Saclay University Faculty of Medicine, Paul-Brousse Hospital, Villejuif, France.
  • Delphine Bachelet
    UMR 1018, INSERM, CESP, Paris-Saclay University Faculty of Medicine, Paul-Brousse Hospital, Villejuif, France.
  • Aude Gleizes
    Clinical Immunology Laboratory, Le Kremlin-Bicêtre Hospital AP-HP, Paris-Saclay University, Le Kremlin-Bicêtre, France.
  • Salima Hacein-Bey-Abina
    Clinical Immunology Laboratory, Le Kremlin-Bicêtre Hospital AP-HP, Paris-Saclay University, Le Kremlin-Bicêtre, France.
  • Matthieu Allez
    Department of Gastroenterology, Saint-Louis Hospital, AP-HP, Paris-Diderot University, Paris, France.
  • Florian Deisenhammer
    Innsbruck Medical, Innsbruck, Austria.
  • Anna Fogdell-Hahn
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
  • Xavier Mariette
    UMR 1184, INSERM, Centre for Immunology of Viral Infections and Autoimmune Diseases, Paris-Saclay University, AP-HP Université Paris-Saclay, Paris, France.
  • Marc Pallardy
    UMR 996, INSERM, Faculty of Pharmacy, Paris-Saclay University, Châtenay-Malabry, France.
  • Philippe Broët
    Research Center, Ste-Justine Hospital, Montreal, QC, Canada.