Capturing the differences between humoral immunity in the normal and tumor environments from repertoire-seq of B-cell receptors using supervised machine learning.

Journal: BMC bioinformatics
PMID:

Abstract

BACKGROUND: The recent success of immunotherapy in treating tumors has attracted increasing interest in research related to the adaptive immune system in the tumor microenvironment. Recent advances in next-generation sequencing technology enabled the sequencing of whole T-cell receptors (TCRs) and B-cell receptors (BCRs)/immunoglobulins (Igs) in the tumor microenvironment. Since BCRs/Igs in tumor tissues have high affinities for tumor-specific antigens, the patterns of their amino acid sequences and other sequence-independent features such as the number of somatic hypermutations (SHMs) may differ between the normal and tumor microenvironments. However, given the high diversity of BCRs/Igs and the rarity of recurrent sequences among individuals, it is far more difficult to capture such differences in BCR/Ig sequences than in TCR sequences. The aim of this study was to explore the possibility of discriminating BCRs/Igs in tumor and in normal tissues, by capturing these differences using supervised machine learning methods applied to RNA sequences of BCRs/Igs.

Authors

  • Hiroki Konishi
    Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
  • Daisuke Komura
    Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
  • Hiroto Katoh
    Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
  • Shinichiro Atsumi
    Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
  • Hirotomo Koda
    Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
  • Asami Yamamoto
    Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
  • Yasuyuki Seto
    Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
  • Masashi Fukayama
    Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
  • Rui Yamaguchi
    The Institute of Medical Science, The University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo, 108-8639, Japan.
  • Seiya Imoto
    The Institute of Medical Science, The University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo, 108-8639, Japan.
  • Shumpei Ishikawa
    Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan. ishum-prm@m.u-tokyo.ac.jp.