BEAVR: a browser-based tool for the exploration and visualization of RNA-seq data

Perampalam, Pirunthan; Dick, Frederick A.

doi:10.1186/s12859-020-03549-8

Cited by 28 publications

(15 citation statements)

References 30 publications

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“…After quality control (error rates of <0.03%), alignments were parsed using STAR (v2.5) program 79 and mapped to the Homo sapiens genome assembly GRCh37 (hg19). Heatmaps of key genes was graph using BEAVR web package (v1.0.10) 80 in Docker. Differential expressions were determined through DESeq2 R package (v1.14.1).…”

Section: Methodsmentioning

confidence: 99%

Timed Notch Inhibition Drives Photoreceptor Fate Specification in Human Retinal Organoids

Chew

Martinez

Chirco

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose Transplanting photoreceptors from human pluripotent stem cell–derived retinal organoids have the potential to reverse vision loss in affected individuals. However, transplantable photoreceptors are only a subset of all cells in the organoids. Hence, the goal of our current study was to accelerate and synchronize photoreceptor differentiation in retinal organoids by inhibiting the Notch signaling pathway at different developmental time-points using a small molecule, PF-03084014 (PF). Methods Human induced pluripotent stem cell– and human embryonic stem cells–derived retinal organoids were treated with 10 µM PF for 3 days starting at day 45 (D45), D60, D90, and D120 of differentiation. Organoids were collected at post-treatment days 14, 28, and 42 and analyzed for progenitor and photoreceptor markers and Notch pathway inhibition by immunohistochemistry (IHC), quantitative PCR, and bulk RNA sequencing ( n = 3–5 organoids from three independent experiments). Results Retinal organoids collected after treatment showed a decrease in progenitor markers (KI67, VSX2, PAX6, and LHX2) and an increase in differentiated pan-photoreceptor markers (OTX2, CRX, and RCVRN) at all organoid stages except D120. PF-treated organoids at D45 and D60 exhibited an increase in cone photoreceptor markers (RXRG and ARR3). PF treatment at D90 revealed an increase in cone and rod photoreceptors markers (ARR3, NRL, and NR2E3). Bulk RNA sequencing analysis mirrored the immunohistochemistry data and quantitative PCR confirmed Notch effector inhibition. Conclusions Timing the Notch pathway inhibition in human retinal organoids to align with progenitor competency stages can yield an enriched population of early cone or rod photoreceptors.

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Section: Methodsmentioning

confidence: 99%

Timed Notch Inhibition Drives Photoreceptor Fate Specification in Human Retinal Organoids

Chew

Martinez

Chirco

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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“…Sequencing reads were aligned to the human genome (Homo_sapiens.GRCh38.92) and read count files were generated using STAR aligner. We used DESeq2 to identify differentially expressed genes (53), and data displays were produced using BEAVR (54). RNA-seq read data is available through GEO226978.…”

Section: Methodsmentioning

confidence: 99%

A genome wide CRISPR screen reveals that HOXA9 promotes Enzalutamide resistance in prostate cancer

Roes,

Dick

2023

Preprint

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Androgen receptor inhibitors are commonly used for prostate cancer treatment, but acquired resistance is a significant problem. Co-deletion of RB and p53 is common in castration resistant prostate cancers, however they are difficult to target pharmacologically. To comprehensively identify gene loss events that contribute to enzalutamide response, we performed a genome-wide CRISPR knockout screen in LNCaP prostate cancer cells. This revealed novel genes implicated in resistance that are largely unstudied. Gene loss events that confer enzalutamide sensitivity are enriched for GSEA categories related to stem cell and epigenetic regulation. We investigated the myeloid lineage stem cell factor HOXA9 as a candidate gene whose loss promotes sensitivity to enzalutamide. Cancer genomic data reveals that HOXA9 overexpression correlates with poor prognosis and characteristics of advanced prostate cancer. In cell culture, HOXA9 depletion sensitizes cells to enzalutamide, whereas overexpression drives enzalutamide resistance. Combination of the HOXA9 inhibitor DB818 with enzalutamide demonstrates synergy. This demonstrates the utility of our CRISPR screen data in discovering new approaches for treating enzalutamide resistant prostate cancer.

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“…Voronoi treemaps have been visualized using the ‘ shinytreemaps ' application (https://m-jahn.shinyapps.io/ShinyTreemaps/) [50]. The browser‐based tool ‘ beavr ’ was utilized to create hierarchical sample clustering and gene set enrichment analyses (GSEA) (FDR correction 10%), Shrinkage estimator: Normal (adaptive normal distribution, genes below 10 reads were excluded from analysis) of RNA‐seq data [51]. Venny 2.1 was utilized to display venn diagrams (https://bioinfogp.cnb.csic.es/tools/venny/index.html) [52].…”

Section: Methodsmentioning

confidence: 99%

Profiling the 3D interaction between germ cell tumors and microenvironmental cells at the transcriptome and secretome level

et al. 2022

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The tumor microenvironment (TM), consisting of the extracellular matrix (ECM), fibroblasts, endothelial cells, and immune cells, might affect tumor invasiveness and the outcome of standard chemotherapy. This study investigated the cross talk between germ cell tumors (GCT) and surrounding TM cells (macrophages, T‐lymphocytes, endothelial cells, and fibroblasts) at the transcriptome and secretome level. Using high‐throughput approaches of three‐dimensional (3D) co‐cultured cellular aggregates, this study offers newly identified pathways to be studied with regard to sensitivity toward cisplatin‐based chemotherapy or tumor invasiveness as a consequence of the cross talk between tumor cells and TM components. Mass‐spectrometry‐based secretome analyses revealed that TM cells secreted factors involved in ECM organization, cell adhesion, angiogenesis, and regulation of insulin‐like growth factor (IGF) transport. To evaluate direct cell–cell contacts, green fluorescent protein (GFP)‐expressing GCT cells and mCherry‐expressing TM cells were co‐cultured in 3D. Afterward, cell populations were separated by flow cytometry and analyzed by RNA sequencing. Correlating the secretome with transcriptome data indicated molecular processes such as cell adhesion and components of the ECM being enriched in most cell populations. Re‐analyses of secretome data with regard to lysine‐ and proline‐hydroxylated peptides revealed a gain in proteins, such as collagens and fibronectin. Cultivation of GCT cells on collagen I/IV‐ or fibronectin‐coated plates significantly elevated adhesive and migratory capacity, while decreasing cisplatin sensitivity of GCT cells. Correspondingly, cisplatin sensitivity was significantly reduced in GCT cells under the influence of conditioned medium from fibroblasts and endothelial cells. This study sheds light on the cross talk between GCT cells and their circumjacent TM, which results in deposition of the ECM and eventually promotes a pro‐tumorigenic environment through enhanced migratory and adhesive capacity, as well as decreased cisplatin sensitivity. Hence, our observations indicate that targeting the ECM and its cellular components might be a novel therapeutic option in combination with cisplatin‐based chemotherapy for GCT patients.

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BEAVR: a browser-based tool for the exploration and visualization of RNA-seq data

Cited by 28 publications

References 30 publications

Timed Notch Inhibition Drives Photoreceptor Fate Specification in Human Retinal Organoids

Timed Notch Inhibition Drives Photoreceptor Fate Specification in Human Retinal Organoids

A genome wide CRISPR screen reveals that HOXA9 promotes Enzalutamide resistance in prostate cancer

Profiling the 3D interaction between germ cell tumors and microenvironmental cells at the transcriptome and secretome level

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