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GSE93211
Homo sapiens
3 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Adoptive T-cell immunotherapy provides a promising approach to cancer therapy. Stem cell memory T (TSCM) cells have been proposed as a new class of memory T cells that possess longevity and a high proliferative potential. It has been shown that CD8+ TSCM cells can be generated in vitro from nave CD8+ T cells via Wnt signaling; however, the methods for inducing TSCM cells from activated or memory T cells remain to be developed.
Publication Title
Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 276 Downloadable Samples
Ion Torrent Proton
Description
We collected and compared samples from the cohort consisted of six groups as follows: methotrexate (MTX) monotherapy, combination therapy of MTX and infliximab (IFX), tocilizumab (TCZ) monotherapy, age- and gender-matched HC, and a small number of synovial fluid samples. In order to reduce variation due to the proportion of cells at each developmental stage, we performed transcriptome analysis after sorting CD4+ and CD8+ T cells according to developmental stage. We created a gene list that was significantly expressed in RA T cells, and revealed that pathways such as mTORC1, IL-2-stat5, Cell cycle and interferon-related genes were significantly enriched among them. Overall design: Examination among healthy controls and patients with rheumatoid arthritis, including before and after treatment
Publication Title
Multi-dimensional analysis identified rheumatoid arthritis-driving pathway in human T cell.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
- Ion Torrent Proton
Description
We compared whole CD4+ and CD8+ T cells from frozen PBMC samples that were collected before and after treatment initiation of each patient with rheumatoid arthritis. Lists consisting of 858 and 950 differentially expressed genes were created from CD4 and CD8, respectively, and these were used for enrichment analysis. As a result, we found that certain pathways were downregulated after TCZ treatment in both CD4+ and CD8+ T cells, including mechanistic target of rapamycin complex 1 (mTORC1) signaling, the IL-2 pathway, and IFN-related genes. Overall design: Examination between before and after tocilizumab treatment of CD4 and CD8 T cell in rheumatoid arthritis patients
Publication Title
Multi-dimensional analysis identified rheumatoid arthritis-driving pathway in human T cell.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Subject
View Samples- Homo sapiens
- 36 Downloadable Samples
- Ion Torrent Proton
Description
We analyzed publicly available mucosal gene expression data from Crohn''s disease (CD) patients pre- and post-infliximab therapy and found that a series of gene expression signature that remains abnormal even if patients achieve clinical remission. Using CMap approach to discover novel therapeutic target for untreatable mechanism of anti-TNFa mAb therapy, we have identified MEK inhibitor exhibiting negatively-correlated effects on reference signature match infliximab therapy untreatable signature. Our findings provide the rationale for testing MEK inhibitor to identify a novel mechanism of action for CD. Gene expression profile was performed to analyze the gene modulation induced by a highly selective MEK inhibitor, and to evaluate whether it normalized reference residual CD signature in vitro. Overall design: LoVo, a human colorectal cancer cell line, was treated with MEK inhibitor for 24 hours across ten dose response conditions (0.03–1,000 nM), and amplicon sequencing was performed on the Ion Torrent platform. Effects of MEK inhibitor were compared with that of DMSO-treated control. MEK inhibitor (compound 33 in Bioorg. Med. Chem. Lett. 22 (2012) 2411 2414))
Publication Title
Gene Signature-Based Approach Identified MEK1/2 as a Potential Target Associated With Relapse After Anti-TNFα Treatment for Crohn's Disease.
Sample Metadata Fields
Disease, Cell line, Treatment, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Ion Torrent Proton
Description
We analyzed publicly available mucosal gene expression data from Crohn''s disease (CD) patients pre- and post-infliximab therapy and found that a series of gene expression signature that remains abnormal even if patients achieve clinical remission. Using CMap approach to discover novel therapeutic target for untreatable mechanism of anti-TNFa mAb therapy, we have identified MEK inhibitor exhibiting negatively-correlated effects on reference signature match infliximab therapy untreatable signature. Our findings provide the rationale for testing MEK inhibitor to identify a novel mechanism of action for CD. Using an activated T cell trasnfer colitis model, a highly selective MEK inhibitor showed therapeutic efficacy and improved the histological changes. To dissect molecular mechanisms, we performed global gene expression profile by RNA-sequencing on the Ion Torrent platform to identify broad scale changes in gene expression treated with MEK inhibitor compared to anti-TNFa mAb. Overall design: Splenocytes from BALB/c female mice were activated with Concanavalin A (4 µg/mL), and recombinant human IL-2 (10 ng/mL, R&D systems) for 3 days. CD4+ T cells were isolated by MACS separation systems, and then 2 x105 activated CD4+ T cells were intravenously injected into female SCID mice (day 0). At day 17, diarrhea score for stool consistency was graded and equally divided into 5 groups as follows: vehicle control, enteric MEK inhibitor microparticles (MPs) at 0.3 mg/kg and at 1 mg/kg, isotype antibody (Isotype mAb) and anti-TNFa antibody (Anti-TNFa mAb). Enteric MEK inhibitor MPs were orally administered once a day from day 17 to day 27. Isotype mAb and anti-TNFa mAb were intraperitoneally injected every 4 days from day 17 at 0.1 mg/mouse. Total RNA from individual cohorts were extracted from the distal part of the colon at day 28, and whole transcriptome sequencing was performed on the Ion Torrent platform. MEK inhibitor (compound 33 in Bioorg. Med. Chem. Lett. 22 (2012) 2411 2414))
Publication Title
Gene Signature-Based Approach Identified MEK1/2 as a Potential Target Associated With Relapse After Anti-TNFα Treatment for Crohn's Disease.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 56 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Multi-omics study was conducted to elucidate the crucial molecular mechanisms of primary Sjgrens syndrome (SS) pathology. We generated multiple data set from well-defined patients with SS, which includes whole-blood transcriptomes, serum proteomes and peripheral immunophenotyping. Based on our newly generated data, we performed an extensive bioinformatic investigation. Our integrative analysis identified SS gene signatures (SGS) dysregulated in widespread omics layers, including epigenomes, mRNAs and proteins. SGS predominantly involved the interferon signature and ADAMs substrates. Besides, SGS was significantly overlapped with SS-causing genes indicated by a genome-wide association study and expression trait loci analyses. Combining the molecular signatures with immunophenotypic profiles revealed that cytotoxic CD8 T cells were associated with SGS. Further, we observed the activation of SGS in cytotoxic CD8 T cells isolated from patients with SS. Our multi-omics investigation identified gene signatures deeply associated with SS pathology and showed the involvement of cytotoxic CD8 T cells. These integrative relations across multiple layers will facilitate our understanding of SS at the system level.
Publication Title
Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren's syndrome.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Multi-omics study was conducted to elucidate the crucial molecular mechanisms of primary Sjgrens syndrome (SS) pathology. We generated multiple data set from well-defined patients with SS, which includes whole-blood transcriptomes, serum proteomes and peripheral immunophenotyping. Based on our newly generated data, we performed an extensive bioinformatic investigation. Our integrative analysis identified SS gene signatures (SGS) dysregulated in widespread omics layers, including epigenomes, mRNAs and proteins. SGS predominantly involved the interferon signature and ADAMs substrates. Besides, SGS was significantly overlapped with SS-causing genes indicated by a genome-wide association study and expression trait loci analyses. Combining the molecular signatures with immunophenotypic profiles revealed that cytotoxic CD8 T cells were associated with SGS. Further, we observed the activation of SGS in cytotoxic CD8 T cells isolated from patients with SS. Our multi-omics investigation identified gene signatures deeply associated with SS pathology and showed the involvement of cytotoxic CD8 T cells. These integrative relations across multiple layers will facilitate our understanding of SS at the system level.
Publication Title
Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren's syndrome.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Multi-omics study was conducted to elucidate the crucial molecular mechanisms of primary Sjgrens syndrome (SS) pathology. We generated multiple data set from well-defined patients with SS, which includes whole-blood transcriptomes, serum proteomes and peripheral immunophenotyping. Based on our newly generated data, we performed an extensive bioinformatic investigation. Our integrative analysis identified SS gene signatures (SGS) dysregulated in widespread omics layers, including epigenomes, mRNAs and proteins. SGS predominantly involved the interferon signature and ADAMs substrates. Besides, SGS was significantly overlapped with SS-causing genes indicated by a genome-wide association study and expression trait loci analyses. Combining the molecular signatures with immunophenotypic profiles revealed that cytotoxic CD8 T cells were associated with SGS. Further, we observed the activation of SGS in cytotoxic CD8 T cells isolated from patients with SS. Our multi-omics investigation identified gene signatures deeply associated with SS pathology and showed the involvement of cytotoxic CD8 T cells. These integrative relations across multiple layers will facilitate our understanding of SS at the system level.
Publication Title
Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren's syndrome.
Sample Metadata Fields
Sex, Specimen part, Disease, Subject
View Samples- Homo sapiens
- 286 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Multi-omics monitoring of drug response in rheumatoid arthritis in pursuit of molecular remission.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 238 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Sustained clinical remission (CR) without drug treatment has not been achieved in patients with rheumatoid arthritis (RA). This implies a substantial difference between CR and the healthy state, but it has yet to be quantified. We report a longitudinal monitoring of the drug response at multi-omics levels in the peripheral blood of patients with RA. Our data reveal that drug treatments alter the molecular profile closer to that of HCs at the transcriptome, serum proteome and immunophenotype level. Patient follow-up suggests that the molecular profile after drug treatments is associated with long-term stable CR. In addition, we identify molecular signatures that are resistant to drug treatments. These signatures are associated with RA independently of known disease severity indexes and are largely explained by the imbalance of neutrophils, monocytes, and lymphocytes. This high-dimensional phenotyping provides a quantitative measure of molecular remission and illustrates a multi-omics approach to understanding drug response.
Publication Title
Multi-omics monitoring of drug response in rheumatoid arthritis in pursuit of molecular remission.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples