Naturally occurring combinations of receptors from single cell transcriptomics in endothelial cells

Published on Apr 15, 2021in bioRxiv
· DOI :10.1101/2021.01.04.425317
Sergii Domanskyi7
Estimated H-index: 7
(MSU: Michigan State University),
Alex Hakansson1
Estimated H-index: 1
(DI: Discovery Institute)
+ 4 AuthorsNapoleone Ferrara179
Estimated H-index: 179
(UCSD: University of California, San Diego)
Sources
Abstract
VEGF inhibitor drugs have been successful, especially in ophthalmology, but not all patients respond to them. Combinations of drugs are likely to be needed for a really effective therapy of angiogenesis-related diseases. In this paper we describe naturally occurring combinations of receptors in endothelial cells that might help to identify targets for drug combinations. We also develop and share a new computational method and a software tool called DECNEO to identify them. Single-cell gene expression data are used to identify a set of co-expressed endothelial cell receptors, conserved among species (mice and human) and enriched, within a network, of connections to up-regulated genes. This set includes several receptors previously shown to play a role in angiogenesis. The reproducibility, evolutionary conservation and role in angiogenesis of the naturally occurring combinations of receptors are supported by multiple highly significant statistical tests from large datasets, including an independent validation set. We also show tissue-specific combinations and, in the case of choroid endothelial cells, consistency with both well-established and recent experimental findings, presented in a separate experimental paper. The results and methods presented here allow one small step forward in the understanding of the syntax of intercellular communication.
📖 Papers frequently viewed together
7 Authors (Sergii Domanskyi, ..., N. Ferrara)
24 Citations
References73
Newest
#1Erick Armingol (UCSD: University of California, San Diego)H-Index: 2
#2Adam Officer (UCSD: University of California, San Diego)H-Index: 1
Last. Nathan E. Lewis (UCSD: University of California, San Diego)H-Index: 43
view all 4 authors...
Cell-cell interactions orchestrate organismal development, homeostasis and single-cell functions. When cells do not properly interact or improperly decode molecular messages, disease ensues. Thus, the identification and quantification of intercellular signalling pathways has become a common analysis performed across diverse disciplines. The expansion of protein-protein interaction databases and recent advances in RNA sequencing technologies have enabled routine analyses of intercellular signalli...
19 CitationsSource
#1Sergii Domanskyi (MSU: Michigan State University)H-Index: 7
#2Alex Hakansson (DI: Discovery Institute)H-Index: 1
Last. Carlo Piermarocchi (MSU: Michigan State University)H-Index: 28
view all 5 authors...
Motivation Analysis of singe cell RNA sequencing (scRNA-seq) typically consists of different steps including quality control, batch correction, clustering, cell identification and characterization, and visualization. The amount of scRNA-seq data is growing extremely fast, and novel algorithmic approaches improving these steps are key to extract more biological information. Here, we introduce: (i) two methods for automatic cell type identification (i.e., without expert curator) based on a voting ...
3 CitationsSource
#1Brent M. Kuenzi (UCSD: University of California, San Diego)H-Index: 9
#2Jisoo Park (UCSD: University of California, San Diego)H-Index: 6
Last. Trey Ideker (UCSD: University of California, San Diego)H-Index: 98
view all 8 authors...
Summary Most drugs entering clinical trials fail, often related to an incomplete understanding of the mechanisms governing drug response. Machine learning techniques hold immense promise for better drug response predictions, but most have not reached clinical practice due to their lack of interpretability and their focus on monotherapies. We address these challenges by developing DrugCell, an interpretable deep learning model of human cancer cells trained on the responses of 1,235 tumor cell lin...
16 CitationsSource
As U.S. particle physicists contemplate their future, they find themselves victims of their own surprising success. Seven years ago, the often-fractious community hammered out its current research road map and rallied around it. Thanks to that unity—and generous budgets— the Department of Energy, the field9s main U.S. sponsor, has already started on almost every project on the list. So this week, as U.S. particle physicists start to drum up new ideas for the next decade in a yearlong Snowmass pr...
2 CitationsSource
#1David M. Morens (NIH: National Institutes of Health)H-Index: 57
#2Anthony S. Fauci (NIH: National Institutes of Health)H-Index: 219
Infectious diseases prevalent in humans and animals are caused by pathogens that once emerged from other animal hosts In addition to these established infections, new infectious diseases periodically emerge In extreme cases they may cause pandemics such as COVID-19;in other cases, dead end infections or smaller epidemics result Established diseases may also re-emerge, for example by extending geographically or by becoming more transmissible or more pathogenic Disease emergence reflects dynamic b...
84 CitationsSource
RANDOMIZATION The Idea of a Randomization Test Examples of Randomization Tests Aspects of Randomization Testing Raised by the Examples Confidence Limits by Randomization Applications of Randomization in Biology and Related Areas Randomization and Observational Studies Chapter Summary THE JACKKNIFE The Jackknife Estimator Applications of Jackknifing in Biology Chapter Summary THE BOOTSTRAP Resampling with Replacement Standard Bootstrap Confidence Limits Simple Percentile Confidence Limits Bias-Co...
4,117 CitationsSource
#2Peter HorbyH-Index: 65
#3W S LimH-Index: 1
Last. Martin J LandrayH-Index: 51
view all 26 authors...
BACKGROUND: Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. METHODS: In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care...
2,123 CitationsSource
#1Thomas Krausgruber (Austrian Academy of Sciences)H-Index: 18
#2Nikolaus Fortelny (Austrian Academy of Sciences)H-Index: 14
Last. Christoph Bock (Medical University of Vienna)H-Index: 72
view all 11 authors...
The mammalian immune system implements a remarkably effective set of mechanisms for fighting pathogens1. Its main components are haematopoietic immune cells, including myeloid cells that control innate immunity, and lymphoid cells that constitute adaptive immunity2. However, immune functions are not unique to haematopoietic cells, and many other cell types display basic mechanisms of pathogen defence3–5. To advance our understanding of immunology outside the haematopoietic system, here we system...
52 CitationsSource
Fibroblast, epithelial and endothelial cells are more than just the scaffold of an organ — it emerges that they communicate with immune cells and are primed to launch organ-specific gene-expression programs for antiviral defence. Fibroblast, epithelial and endothelial cells aid organ-specific defence.
2 CitationsSource
#1Oscar Franzén (KI: Karolinska Institutet)H-Index: 22
#2Johan Björkegren (KI: Karolinska Institutet)H-Index: 32
SUMMARY: Single cell RNA sequencing is a technology to measure gene expression in single cells. It has enabled discovery of new cell types and established cell type atlases of tissues and organs. The widespread adoption of single cell RNA-seq has created a need for user-friendly software for data analysis. We have developed a web server, alona, that incorporates several of the most popular single cell analysis algorithms into a flexible pipeline. alona can perform quality filtering, normalizatio...
10 CitationsSource
Cited By0
Newest