Systematic single-cell pathway analysis to characterize early T cell activation

Jack A. Bibby, Divyansh Agarwal, Tilo Freiwald, Natalia Kunz, Nicolas S. Merle, Erin E. West, Parul Singh, Andre Larochelle, Fariba Chinian, Somabha Mukherjee, Behdad Afzali, Claudia Kemper*, Nancy R. Zhang*

*Corresponding author for this work
10 Citations (Scopus)

Abstract

Pathway analysis is a key analytical stage in the interpretation of omics data, providing a powerful method for detecting alterations in cellular processes. We recently developed a sensitive and distribution-free statistical framework for multisample distribution testing, which we implement here in the open-source R package single-cell pathway analysis (SCPA). We demonstrate the effectiveness of SCPA over commonly used methods, generate a scRNA-seq T cell dataset, and characterize pathway activity over early cellular activation. This reveals regulatory pathways in T cells, including an intrinsic type I interferon system regulating T cell survival and a reliance on arachidonic acid metabolism throughout T cell activation. A systems-level characterization of pathway activity in T cells across multiple tissues also identifies alpha-defensin expression as a hallmark of bone-marrow-derived T cells. Overall, this work provides a widely applicable tool for single-cell pathway analysis and highlights regulatory mechanisms of T cells.

Original languageEnglish
Article number111697
JournalCell Reports
Volume41
Issue number8
ISSN2211-1247
DOIs
Publication statusPublished - 22.11.2022

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

DFG Research Classification Scheme

  • 204-05 Immunology

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