Systematic single-cell pathway analysis to characterize early T cell activation.
CP: Immunology
SCPA
T cell
arachidonic acid
cytokines
gene set
metabolism
pathway analysis
single-cell RNA-seq
single-cell pathway analysis
type I interferon
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
22 11 2022
22 11 2022
Historique:
received:
31
01
2022
revised:
06
07
2022
accepted:
31
10
2022
entrez:
23
11
2022
pubmed:
24
11
2022
medline:
26
11
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36417885
pii: S2211-1247(22)01571-6
doi: 10.1016/j.celrep.2022.111697
pmc: PMC10704209
mid: NIHMS1946770
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
111697Subventions
Organisme : NHGRI NIH HHS
ID : R01 HG006137
Pays : United States
Organisme : NCI NIH HHS
ID : U2C CA233285
Pays : United States
Organisme : Intramural NIH HHS
ID : Z99 HL999999
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA HL006223
Pays : United States
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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