Knowledge-based classification of fine-grained immune cell types in single-cell RNA-Seq data.

Journal: Briefings in bioinformatics
Published Date:

Abstract

Single-cell RNA sequencing (scRNA-Seq) is an emerging strategy for characterizing immune cell populations. Compared to flow or mass cytometry, scRNA-Seq could potentially identify cell types and activation states that lack precise cell surface markers. However, scRNA-Seq is currently limited due to the need to manually classify each immune cell from its transcriptional profile. While recently developed algorithms accurately annotate coarse cell types (e.g. T cells versus macrophages), making fine distinctions (e.g. CD8+ effector memory T cells) remains a difficult challenge. To address this, we developed a machine learning classifier called ImmClassifier that leverages a hierarchical ontology of cell type. We demonstrate that its predictions are highly concordant with flow-based markers from CITE-seq and outperforms other tools (+15% recall, +14% precision) in distinguishing fine-grained cell types with comparable performance on coarse ones. Thus, ImmClassifier can be used to explore more deeply the heterogeneity of the immune system in scRNA-Seq experiments.

Authors

  • Xuan Liu
    Department of Electrical and Computer Engineering, New Jersey Institute of Technology, University Heights, Newark, NJ 07102, USA.
  • Sara J C Gosline
    Sage Bionetworks, Seattle, WA 98109, USA.
  • Lance T Pflieger
    Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Pierre Wallet
    Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Archana Iyer
    Center for Cancer Systems Immunology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Justin Guinney
    Computational Oncology, Sage Bionetworks, Seattle, Washington.
  • Andrea H Bild
    Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Jeffrey T Chang
    School of Biomedical Informatics.