Expression Atlas update: from tissues to single cells

Papatheodorou, Irene; Moreno, Pablo; Manning, Jonathan; Fuentes, Alfonso Muñoz-Pomer; George, Nancy; Fexová, Silvie; Fonseca, Nuno A.; Füllgrabe, Anja; Green, Matthew; Huang, Ni; Huerta, Laura; Iqbal, Haider; Jianu, Monica; Mohammed, Suhaib; Zhao, Lingyun; Jarnuczak, Andrew F.; Jupp, Simon; Marioni, John C.; Meyer, Kerstin B.; Petryszak, Robert; Prada-Medina, César Augusto; Talavera-López, Carlos; Teichmann, Sarah A.; Vizcaíno, Juan Antonio; Brāzma, Alvis

doi:10.1093/nar/gkz947

Cited by 409 publications

(495 citation statements)

References 23 publications

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“…The analysis described in this paper was performed using Python, Excel, and Graphpad Prism. Gene expression data was acquired from the Gene Expression Omnibus (GEO) 89 , the GTEx portal 15 , the Broad Institute TCGA Firehose 90 , the Human Cell Atlas 91 , and the Single-Cell Expression Atlas 92 , as described below. For microarray datasets, probeset definitions were downloaded from GEO, and probes mapping to the same gene were collapsed by averaging.…”

Section: Methodsmentioning

confidence: 99%

Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract

Smith

Sausville

Girish

et al. 2020

Preprint

100

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The coronavirus SARS-CoV-2 has infected more than 600,000 people and has overwhelmed hospital systems around the world. However, the factors mediating fatal SARS-CoV-2 infections are poorly understood. Here, we show that cigarette smoke causes a dose-dependent upregulation of Angiotensin Converting Enzyme 2 (ACE2), the SARS-CoV-2 receptor, in rodent and human lungs. Using single-cell sequencing data, we demonstrate that ACE2 is expressed in a subset of epithelial cells that line the respiratory tract, including goblet cells, club cells, and alveolar type 2 cells. Chronic smoke exposure triggers a protective expansion of mucus-secreting goblet cells and a concomitant increase in ACE2 expression. In contrast, quitting smoking causes a decrease in lung ACE2 levels. Taken together, these results may partially explain why smokers are particularly likely to develop severe SARS-CoV-2 infections, and they suggest that quitting smoking could lessen coronavirus susceptibility.

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Section: Methodsmentioning

confidence: 99%

Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract

Smith

Sausville

Girish

et al. 2020

Preprint

100

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“…• Single-Cell Expression Atlas (Papatheodorou et al 2020) To understand the current landscape of interactive analysis and visualisation tools we compared (Table 1) several of the most popular based on their general qualities. Our results show that each tool has particular advantages and disadvantages and as such a simple ranking cannot be achieved.…”

Section: Discussionmentioning

confidence: 99%

Comparison of visualisation tools for single-cell RNAseq data

Cakir

Prete

Huang

et al. 2020

Preprint

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In the last decade, single cell RNAseq (scRNAseq) datasets have grown from a single cell to millions of cells. Due to its high dimensionality, the scRNAseq data contains a lot of valuable information, however, it is not always feasible to visualise and share it in a scientific report or an article publication format. Recently, a lot of interactive analysis and visualisation tools have been developed to address this issue and facilitate knowledge transfer in the scientific community. In this study, we review and compare several of the currently available analysis and visualisation tools and benchmark those that allow to visualize the scRNAseq data on the web and share it with others. To address the problem of format compatibility for most visualisation tools, we have also developed a user-friendly R package, sceasy , which allows users to convert their own scRNAseq datasets into a specific data format for visualisation.

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“…The analysis of the single-cell RNA-seq data from the Tabula Muris consortium 19 was accessed on the Single Cell Expression Atlas 41 from EMBL-EBI at https://www.ebi.ac.uk/gxa/sc/home on March 4th, 2020 and analyzed online on this platform.…”

Section: Methodsmentioning

confidence: 99%

The murine Microenvironment Cell Population counter method to estimate abundance of tissue-infiltrating immune and stromal cell populations in murine samples using gene expression

Petitprez

Lévy

Sun

et al. 2020

Preprint

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129/150 words) 15Quantifying tissue-infiltrating immune and stromal cells provides clinically relevant information for 16 various diseases, notably cancer. While numerous methods allow to quantify immune or stromal cells 17 in human tissue samples based on transcriptomic data, very few are available for mouse studies. 18Here, we introduce murine Microenvironment Cell Population counter (mMCP-counter), a method 19 based on highly specific transcriptomic markers that allow to accurately quantify 12 immune and 4 20 stromal murine cell populations. We validated mMCP-counter with flow cytometry data. We also 21 showed that mMCP-counter outperforms existing methods. We showed in mouse models of 22 mesothelioma and kidney cancer that mMCP-counter quantification scores are predictive of response 23 to immune checkpoint blockade Finally, we illustrated mMCP-counter's potential to analyze immune 24 impacts of Alzheimer's disease. mMCP-counter is available as an R package from GitHub: 25 https://github.com/cit-bioinfo/mMCP-counter.26 3 Main text (2,967 words) 27 28 Introduction 29 30 For a large number of diseases, such as inflammatory diseases or cancer, it is often crucial to 31 accurately determine the cellular composition of the tissue where the pathology develops, in terms of 32 immune and stromal cell populations. An array of methods are available to obtain these data from 33 human samples, either by immunochemistry or cytometry, or computationally from transcriptomics 34 data 1 . 35The analysis of the immune and stromal composition of tissues is particularly critical in cancer studies. 36Indeed, tumors are highly heterogeneous tissues which are infiltrated by a variety of immune and 37 stromal cells 2 . It was shown that immune cell densities were associated with prognosis 3 : For instance, 38CD8 + T cells density correlates with prolonged patient survival in most cancers, whereas M2-polarized 39 macrophages are generally associated with a poor prognosis 3 . 40The transcriptome of a bulk tissue sample yields the averaged expression of genes across all the cells 41 present in the sample. As some genes are uniquely expressed in some specific cell populations, their 42 expression can be used to determine the abundance of the underlying cell populations. Using this 43 property, we have previously reported on MCP-counter, a method designed to quantify the immune 44 infiltrate of heterogeneous human tissues 4 , currently one of the best performing methods for this 45 purpose 5 . 46While murine models are widely used to decipher the pathophysiological mechanisms of various 47 diseases, including inflammatory diseases and cancer, the computational methods currently available 48 to measure the immune and stromal composition of murine tissues are few and limited, as compared 49 to what is available for human samples 6 . 50Here, we introduce murine Microenvironment Cell Populations counter (mMCP-counter), the 51 adaptation of the MCP-counter method to murine samples (Figure 1), which was made possible 52 thanks to the release o...

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Expression Atlas update: from tissues to single cells

Cited by 409 publications

References 23 publications

Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract

Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract

Comparison of visualisation tools for single-cell RNAseq data

The murine Microenvironment Cell Population counter method to estimate abundance of tissue-infiltrating immune and stromal cell populations in murine samples using gene expression

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