%0 Journal Article %1 Rade2023-eh %A Rade, Michael %A Böhlen, Sebastian %A Neuhaus, Vanessa %A Löffler, Dennis %A Blumert, Conny %A Merz, Maximilian %A Köhl, Ulrike %A Dehmel, Susann %A Sewald, Katherina %A Reiche, Kristin %D 2023 %J Genome Biol. %K topic_lifescience Biomarkers; Gene Non-negative T-cell Temporal Time Transcriptome activation; expression; factorization; gene matrix profiles; series; %N 1 %P 287 %T A time-resolved meta-analysis of consensus gene expression profiles during human T-cell activation %V 24 %X BACKGROUND: The coordinated transcriptional regulation of activated T-cells is based on a complex dynamic behavior of signaling networks. Given an external stimulus, T-cell gene expression is characterized by impulse and sustained patterns over the course. Here, we analyze the temporal pattern of activation across different T-cell populations to develop consensus gene signatures for T-cell activation. RESULTS: Here, we identify and verify general biomarker signatures robustly evaluating T-cell activation in a time-resolved manner. We identify time-resolved gene expression profiles comprising 521 genes of up to 10 disjunct time points during activation and different polarization conditions. The gene signatures include central transcriptional regulators of T-cell activation, representing successive waves as well as sustained patterns of induction. They cover sustained repressed, intermediate, and late response expression rates across multiple T-cell populations, thus defining consensus biomarker signatures for T-cell activation. In addition, intermediate and late response activation signatures in CAR T-cell infusion products are correlated to immune effector cell-associated neurotoxicity syndrome. CONCLUSION: This study is the first to describe temporally resolved gene expression patterns across T-cell populations. These biomarker signatures are a valuable source, e.g., monitoring transcriptional changes during T-cell activation with a reasonable number of genes, annotating T-cell states in single-cell transcriptome studies, or assessing dysregulated functions of human T-cell immunity.

@article{Rade2023-eh, abstract = {BACKGROUND: The coordinated transcriptional regulation of activated T-cells is based on a complex dynamic behavior of signaling networks. Given an external stimulus, T-cell gene expression is characterized by impulse and sustained patterns over the course. Here, we analyze the temporal pattern of activation across different T-cell populations to develop consensus gene signatures for T-cell activation. RESULTS: Here, we identify and verify general biomarker signatures robustly evaluating T-cell activation in a time-resolved manner. We identify time-resolved gene expression profiles comprising 521 genes of up to 10 disjunct time points during activation and different polarization conditions. The gene signatures include central transcriptional regulators of T-cell activation, representing successive waves as well as sustained patterns of induction. They cover sustained repressed, intermediate, and late response expression rates across multiple T-cell populations, thus defining consensus biomarker signatures for T-cell activation. In addition, intermediate and late response activation signatures in CAR T-cell infusion products are correlated to immune effector cell-associated neurotoxicity syndrome. CONCLUSION: This study is the first to describe temporally resolved gene expression patterns across T-cell populations. These biomarker signatures are a valuable source, e.g., monitoring transcriptional changes during T-cell activation with a reasonable number of genes, annotating T-cell states in single-cell transcriptome studies, or assessing dysregulated functions of human T-cell immunity.}, added-at = {2024-09-10T10:41:24.000+0200}, author = {Rade, Michael and B{\"o}hlen, Sebastian and Neuhaus, Vanessa and L{\"o}ffler, Dennis and Blumert, Conny and Merz, Maximilian and K{\"o}hl, Ulrike and Dehmel, Susann and Sewald, Katherina and Reiche, Kristin}, biburl = {https://puma.scadsai.uni-leipzig.de/bibtex/2beabd77371074101f3215f13072cd719/scadsfct}, interhash = {00e452d4dfdc1f585a3aea0f741b25dd}, intrahash = {beabd77371074101f3215f13072cd719}, journal = {Genome Biol.}, keywords = {topic_lifescience Biomarkers; Gene Non-negative T-cell Temporal Time Transcriptome activation; expression; factorization; gene matrix profiles; series;}, language = {en}, month = dec, number = 1, pages = 287, timestamp = {2024-11-22T15:48:26.000+0100}, title = {A time-resolved meta-analysis of consensus gene expression profiles during human T-cell activation}, volume = 24, year = 2023 }