Machine learning methods enable predictive modeling of antibody feature:function relationships in RV144 vaccinees.

Journal: PLoS computational biology
PMID:

Abstract

The adaptive immune response to vaccination or infection can lead to the production of specific antibodies to neutralize the pathogen or recruit innate immune effector cells for help. The non-neutralizing role of antibodies in stimulating effector cell responses may have been a key mechanism of the protection observed in the RV144 HIV vaccine trial. In an extensive investigation of a rich set of data collected from RV144 vaccine recipients, we here employ machine learning methods to identify and model associations between antibody features (IgG subclass and antigen specificity) and effector function activities (antibody dependent cellular phagocytosis, cellular cytotoxicity, and cytokine release). We demonstrate via cross-validation that classification and regression approaches can effectively use the antibody features to robustly predict qualitative and quantitative functional outcomes. This integration of antibody feature and function data within a machine learning framework provides a new, objective approach to discovering and assessing multivariate immune correlates.

Authors

  • Ickwon Choi
    Department of Computer Science, Dartmouth College, Hanover, New Hampshire, United States of America.
  • Amy W Chung
    Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston, Massachusetts, United States of America.
  • Todd J Suscovich
    Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston, Massachusetts, United States of America.
  • Supachai Rerks-Ngarm
    Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand.
  • Punnee Pitisuttithum
    Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Sorachai Nitayaphan
    Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
  • Jaranit Kaewkungwal
    Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Robert J O'Connell
    Department of Retrovirology, U.S. Army Medical Component, AFRIMS, Bangkok, Thailand.
  • Donald Francis
    Global Solutions for Infectious Diseases (GSID), South San Francisco, California, United States of America.
  • Merlin L Robb
    US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America; Henry Jackson Foundation HIV Program, US Military HIV Research Program, Bethesda, Maryland, United States of America.
  • Nelson L Michael
    US Military HIV Research Program, Bethesda, MD, USA; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Jerome H Kim
    US Military HIV Research Program, Bethesda, MD, USA; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Galit Alter
    Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Boston, Massachusetts, United States of America.
  • Margaret E Ackerman
    Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, United States of America.
  • Chris Bailey-Kellogg
    Department of Computer Science, Dartmouth College, Hanover, New Hampshire, United States of America.