DRPPM-EASY: A Web-Based Framework for Integrative Analysis of Multi-Omics Cancer Datasets

Obermayer, Alyssa; Dong, Li; Hu, Qianqian; Golden, Michael; Noble, Jerald D.; Rodríguez, Paulo C.; Robinson, Timothy J.; Teng, Mingxiang; Tan, Aik-Choon; Shaw, Timothy I.

doi:10.3390/biology11020260

Cited by 7 publications

(4 citation statements)

References 37 publications

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“…This PDF file includes: Figs. S1 to S9 References (74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85) Other Supplementary Material for this manuscript includes the following: Data files S1 and S2 MDAR Reproducibility Checklist View/request a protocol for this paper from Bio-protocol.…”

Section: Supplementary Materialsmentioning

confidence: 99%

Bcl11b sustains multipotency and restricts effector programs of intestinal-resident memory CD8 ⁺ T cells

et al. 2023

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The networks of transcription factors (TFs) that control intestinal-resident memory CD8 + T (T RM ) cells, including multipotency and effector programs, are poorly understood. In this work, we investigated the role of the TF Bcl11b in T RM cells during infection with Listeria monocytogenes using mice with post-activation, conditional deletion of Bcl11b in CD8 + T cells. Conditional deletion of Bcl11b resulted in increased numbers of intestinal T RM cells and their precursors as well as decreased splenic effector and circulating memory cells and precursors. Loss of circulating memory cells was in part due to increased intestinal homing of Bcl11b −/− circulating precursors, with no major alterations in their programs. Bcl11b −/− T RM cells had altered transcriptional programs, with diminished expression of multipotent/multifunctional (MP/MF) program genes, including Tcf7 , and up-regulation of the effector program genes, including Prdm1. Bcl11b also limits the expression of Ahr, another TF with a role in intestinal CD8 + T RM cell differentiation. Deregulation of T RM programs translated into a poor recall response despite T RM cell accumulation in the intestine. Reduced expression of MP/MF program genes in Bcl11b −/− T RM cells was linked to decreased chromatin accessibility and a reduction in activating histone marks at these loci. In contrast, the effector program genes displayed increased activating epigenetic status. These findings demonstrate that Bcl11b is a frontrunner in the tissue residency program of intestinal memory cells upstream of Tcf1 and Blimp1, promoting multipotency and restricting the effector program.

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Section: Supplementary Materialsmentioning

confidence: 99%

Bcl11b sustains multipotency and restricts effector programs of intestinal-resident memory CD8 ⁺ T cells

et al. 2023

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“…Interestingly, our analysis further revealed two distinct population of TRM-progenitor effector cells, which both contained high IL7R but with varying mid to high expression of GZMB (Figure 6). To facilitate an integrative gene expression analysis, samples can also be grouped based on genotype and explored by the DRPPM-EASY app (Obermayer et al 2022). Finally, prognosis biomarkers derived from each cluster or cell types can also be evaluated using the PATH-SURVEYOR suite (Obermayer et al 2023).…”

Section: Single-cell Rnaseq Shiny App Explorermentioning

confidence: 99%

BERLIN: Basic Explorer for single-cell RNAseq analysis and cell Lineage Determination

Nobles

Obermayer

Yang

et al. 2023

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Single-cell RNA sequencing has revolutionized the study of immuno-oncology, cancer biology, and developmental biology by enabling the joint characterization of gene expression and cellular heterogeneity in a single platform. As of July 2023, the Gene Expression Omnibus now contains over 4000 published single-cell data sets, providing an invaluable opportunity for reanalysis to identify new cell types or cellular states as well as their defining transcriptional programs. To facilitate the reprocessing of these public datasets, we have devised a single-cell RNA sequencing analysis framework for data retrieval, quality control, expression normalization, dimension reduction, cell clustering, and data integration. Additionally, we have developed a Shiny App visualization platform that enables the exploration of gene expression, cell type annotations, and cell lineages through a user interface. We performed a re-analysis of single-cell RNAseq data generated from acute myeloid leukemia and tumor-reactive lymphocytes and found our pipeline to faithfully recapitulated the cell type assignment as well as expected lineage trajectories. Altogether, we present BERLIN, a single-cell RNAseq analysis pipeline that facilitates the integration and public dissemination of results from the reanalysis.

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“…Gene set enrichment analysis (GSEA) was performed using GSEA software version 4.0.3 (Massachusetts Institute of Technology); signal-to-noise ranking criteria was used as a default. ssGSEA 30,31 was used to derive a signature score for each progenitor myeloid subset as implemented in DRPPM-EASY 32 . Gene set was derived from mRNA profiling of HSC, GMP, CMP, MEP, and MPP as described 28 .…”

Section: Rna-sequencing and Bioinformatic Analysesmentioning

confidence: 99%

CBFA2T3-GLIS2-dependent pediatric acute megakaryoblastic leukemia is driven by GLIS2 and sensitive to Navitoclax

Neault

Lebert-Ghali

Fournier

et al. 2022

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Pediatric acute megakaryoblastic leukemia (AMKL) is an aggressive, uncurable blood cancer associated with poor therapeutic response and high mortality. We developed CBFA2T3-GLIS2-driven mouse models of AMKL that recapitulate the phenotypic and transcriptional signatures of the human disease. We show that an activating Ras mutation, which occurs in human AMKL, increased the penetrance and decreased the latency of CBF2AT3-GLIS2-driven AMKL. CBFA2T3-GLIS2 and GLIS2 modulate similar transcriptional networks. We uncover the dominant oncogenic properties of GLIS2, which trigger AMKL in cooperation with oncogenic Ras. We find that both CBFA2T3-GLIS2 and GLIS2 alter the expression of numerous BH3-only proteins, causing AMKL cell sensitivity to the BCL-2 inhibitor navitoclax both in vitro and in vivo, suggesting a novel therapeutic option for pediatric patients suffering from CBFA2T3-GLIS2-driven AMKL.

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DRPPM-EASY: A Web-Based Framework for Integrative Analysis of Multi-Omics Cancer Datasets

Cited by 7 publications

References 37 publications

Bcl11b sustains multipotency and restricts effector programs of intestinal-resident memory CD8 ⁺ T cells

Bcl11b sustains multipotency and restricts effector programs of intestinal-resident memory CD8 ⁺ T cells

BERLIN: Basic Explorer for single-cell RNAseq analysis and cell Lineage Determination

CBFA2T3-GLIS2-dependent pediatric acute megakaryoblastic leukemia is driven by GLIS2 and sensitive to Navitoclax

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DRPPM-EASY: A Web-Based Framework for Integrative Analysis of Multi-Omics Cancer Datasets

Cited by 7 publications

References 37 publications

Bcl11b sustains multipotency and restricts effector programs of intestinal-resident memory CD8 + T cells

Bcl11b sustains multipotency and restricts effector programs of intestinal-resident memory CD8 + T cells

BERLIN: Basic Explorer for single-cell RNAseq analysis and cell Lineage Determination

CBFA2T3-GLIS2-dependent pediatric acute megakaryoblastic leukemia is driven by GLIS2 and sensitive to Navitoclax

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Bcl11b sustains multipotency and restricts effector programs of intestinal-resident memory CD8 ⁺ T cells

Bcl11b sustains multipotency and restricts effector programs of intestinal-resident memory CD8 ⁺ T cells