Machine learning can identify newly diagnosed patients with CLL at high risk of infection.

Journal: Nature communications
Published Date:

Abstract

Infections have become the major cause of morbidity and mortality among patients with chronic lymphocytic leukemia (CLL) due to immune dysfunction and cytotoxic CLL treatment. Yet, predictive models for infection are missing. In this work, we develop the CLL Treatment-Infection Model (CLL-TIM) that identifies patients at risk of infection or CLL treatment within 2 years of diagnosis as validated on both internal and external cohorts. CLL-TIM is an ensemble algorithm composed of 28 machine learning algorithms based on data from 4,149 patients with CLL. The model is capable of dealing with heterogeneous data, including the high rates of missing data to be expected in the real-world setting, with a precision of 72% and a recall of 75%. To address concerns regarding the use of complex machine learning algorithms in the clinic, for each patient with CLL, CLL-TIM provides explainable predictions through uncertainty estimates and personalized risk factors.

Authors

  • Rudi Agius
    Department of Mathematics and Computer Science, Technical University of Denmark, Lyngby, Denmark.
  • Christian Brieghel
    Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  • Michael A Andersen
    Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  • Alexander T Pearson
    Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.
  • Bruno Ledergerber
    University of Zurich, Zurich, Switzerland.
  • Alessandro Cozzi-Lepri
    CREME Centre, IGH University College London, London, UK.
  • Yoram Louzoun
    Department of Mathematics, Bar-Ilan University, Ramat-Gan, Israel.
  • Christen L Andersen
    Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  • Jacob Bergstedt
    Human Evolutionary Genetics Unit, Institut Pasteur, Paris, France.
  • Jakob H von Stemann
    Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  • Mette Jørgensen
    Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  • Man-Hung Eric Tang
    Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  • Magnus Fontes
    Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  • Jasmin Bahlo
    Department of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University Hospital, Cologne, Germany.
  • Carmen D Herling
    Department of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University Hospital, Cologne, Germany.
  • Michael Hallek
    Department of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University Hospital, Cologne, Germany.
  • Jens Lundgren
    Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  • Cameron Ross MacPherson
    Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  • Jan Larsen
    Department of Mathematics and Computer Science, Technical University of Denmark, Lyngby, Denmark.
  • Carsten U Niemann
    Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. Carsten.utoft.niemann@regionh.dk.