Systematic single-cell pathway analysis to characterize early T cell activation
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Systematic single-cell pathway analysis to characterize early T cell activation. / Bibby, JA; Agarwal, D; Freiwald, T; Kunz, N; Merle, NS; West, EE; Singh, P; Larochelle, A; Chinian, F; Mukherjee, S; Afzali, B; Kemper, C; Zhang, NR.
In: CELL REP, Vol. 41, No. 8, 111697, 22.11.2022, p. 111697.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Systematic single-cell pathway analysis to characterize early T cell activation
AU - Bibby, JA
AU - Agarwal, D
AU - Freiwald, T
AU - Kunz, N
AU - Merle, NS
AU - West, EE
AU - Singh, P
AU - Larochelle, A
AU - Chinian, F
AU - Mukherjee, S
AU - Afzali, B
AU - Kemper, C
AU - Zhang, NR
PY - 2022/11/22
Y1 - 2022/11/22
N2 - 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.
AB - 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.
UR - http://europepmc.org/abstract/med/36417885
U2 - 10.1016/j.celrep.2022.111697
DO - 10.1016/j.celrep.2022.111697
M3 - SCORING: Journal article
C2 - 36417885
VL - 41
SP - 111697
JO - CELL REP
JF - CELL REP
SN - 2211-1247
IS - 8
M1 - 111697
ER -