Use ggbreak to Effectively Utilize Plotting Space to Deal With Large Datasets and Outliers

Microglia are known for important phagocytic functions in the vertebrate retina. Reports also suggest that Müller glia have phagocytic capacity, though the relative levels and contexts in which this occurs remain to be thoroughly examined. Here, we investigate Müller glial engulfment of dying cells in the developing zebrafish retina in the presence and absence of microglia, using a genetic mutant in which microglia do not develop. We show that in normal conditions clearance of dying cells is dominated by microglia; however, Müller glia do have a limited clearance role. In retinas lacking intact microglial populations, we found a striking increase in the engulfment load assumed by the Müller glia, which displayed prominent cellular compartments containing apoptotic cells, several of which localized with the early phagosome/endosome marker Rab5. Consistent with increased engulfment, lysosomal staining was also increased in Müller glia in the absence of microglia. Increased engulfment load led to evidence of Müller glia reactivity including upregulation of gfap but did not trigger cell cycle re‐entry by differentiated Müller glia. Our work provides important insight into the phagocytic capacity of Müller glia and the ability for compensatory functions and downstream effects. Therefore, effects of microglial deficiency or depletion on other glial cell types should be well‐considered in experimental manipulations, in neurodegenerative disease, and in therapeutic approaches that target microglia. Our findings further justify future work to understand differential mechanisms and contexts of phagocytosis by glial cells in the central nervous system, and the significance of these mechanisms in health and disease.

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“…Plotting and statistical analysis were performed in the R coding environment (R Core Team, 2017; Xu et al, 2021)…”

Section: Discussionmentioning

confidence: 99%

“…Plotting and statistical analysis were performed in the R coding environment (R Core Team, 2017; Xu et al, 2021). All data was assessed for normality and homogeneity of variances prior to selecting the statistical test.…”

Section: Methodsmentioning

confidence: 99%

Compensatory engulfment and Müller glia reactivity in the absence of microglia

Thiel

Blume

Mitchell

2022

Glia

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“…Canonical pathways (reactome) gene set for gene set enrichment analysis was retrieved using the msigdbr R package v.7.4.1. Other R packages used to analyze and visualize RNA-seq data include tidyverse v.1.3.1 ( 89 ), cowplot v.1.1.1, ggbreak v.0.0.9 ( 90 ), ggrepel v.0.9.1, RColorBrewer v.1.1-2, gplots v.3.1.3, and enrichplot v.1.14.2 with scripts from DIY.transcriptomics ( 91 ).…”

Section: Methodsmentioning

confidence: 99%

Overexpression screen of chromosome 21 genes reveals modulators of Sonic hedgehog signaling relevant to Down syndrome

Moyer

Fernandez

et al. 2022

Preprint

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Dysregulation of Sonic hedgehog (SHH) signaling may contribute to multiple Down syndrome-associated phenotypes, including cerebellar hypoplasia, congenital heart defects, craniofacial and skeletal dysmorphologies, and Hirschsprung disease. Granule cell precursors isolated from the developing cerebellum of Ts65Dn mice are less responsive to the mitogenic effects of SHH than euploid cells, and a single postnatal dose of the SHH pathway agonist SAG rescues cerebellar morphology and performance on learning and memory tasks in Ts65Dn mice. SAG treatment also normalizes expression levels of OLIG2 in neural progenitor cells derived from human trisomy 21 iPSCs. However, despite evidence that activating SHH signaling can ameliorate some Down syndrome-associated phenotypes, chromosome 21 does not encode any components of the canonical SHH pathway. Here, we screened 163 chromosome 21 cDNAs in a series of SHH-responsive cell lines to identify chromosome 21 genes that modulate SHH signaling. We confirmed overexpression of trisomic candidate genes using RNA-seq in Ts65Dn and TcMAC21 cerebellum. Our study indicates that some chromosome 21 genes, including DYRK1A, upregulate SHH signaling while others, such as HMGN1 and MIS18A, inhibit SHH signaling. Overexpression of genes involved in chromatin structure and mitosis, but not genes previously implicated in ciliogenesis, regulate the SHH pathway. Our data suggest that cerebellar hypoplasia and other phenotypes related to aberrant SHH signaling arise from the net effect of trisomy for multiple chromosome 21 genes rather than the overexpression of a single trisomic gene. Identifying which chromosome 21 genes modulate SHH signaling may suggest new therapeutic avenues for ameliorating Down syndrome phenotypes.

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“…OPAL (commit edb6f41 in dev branch) [29] is used to assess taxonomic metagenome profilers. R 4.1.2 [57], ggplot2 3.3.5 [58], ggbreak 0.0.9 [59], and some other R packages are used for data visualization.…”

Section: Methodsmentioning

confidence: 99%

KMCP: accurate metagenomic profiling of both prokaryotic and viral populations by pseudo-mapping

Shen

Xiang

Huang

et al. 2022

Preprint

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A growing number of microbial reference genomes enable better metagenomic profiling accuracy yet put higher requirements on the indexing efficiency, database size, and runtime of taxonomic profilers. Besides, most profilers focused mainly on bacterial, archaeal, and fungal populations with less attention on viral communities. We present KMCP, a novel k-mer based metagenomic profiling tool that introduces genomic positions to k-mers by splitting the reference genomes into chunks. Benchmarking results on both simulated and real data demonstrate that KMCP not only allows for accurate taxonomic profiling of archaea, bacteria, and viral populations from metagenomic shotgun sequence data, but also provides confident pathogen detection for infectious clinical samples of low depth. KMCP is implemented in Go and is available as open-source software, under MIT, at https://github.com/shenwei356/kmcp.

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Use ggbreak to Effectively Utilize Plotting Space to Deal With Large Datasets and Outliers

Cited by 142 publications

References 10 publications

Compensatory engulfment and Müller glia reactivity in the absence of microglia

Compensatory engulfment and Müller glia reactivity in the absence of microglia

Overexpression screen of chromosome 21 genes reveals modulators of Sonic hedgehog signaling relevant to Down syndrome

KMCP: accurate metagenomic profiling of both prokaryotic and viral populations by pseudo-mapping

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