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      Comparison of methods and resources for cell-cell communication inference from single-cell RNA-Seq data

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          Abstract

          The growing availability of single-cell data, especially transcriptomics, has sparked an increased interest in the inference of cell-cell communication. Many computational tools were developed for this purpose. Each of them consists of a resource of intercellular interactions prior knowledge and a method to predict potential cell-cell communication events. Yet the impact of the choice of resource and method on the resulting predictions is largely unknown. To shed light on this, we systematically compare 16 cell-cell communication inference resources and 7 methods, plus the consensus between the methods’ predictions. Among the resources, we find few unique interactions, a varying degree of overlap, and an uneven coverage of specific pathways and tissue-enriched proteins. We then examine all possible combinations of methods and resources and show that both strongly influence the predicted intercellular interactions. Finally, we assess the agreement of cell-cell communication methods with spatial colocalisation, cytokine activities, and receptor protein abundance and find that predictions are generally coherent with those data modalities. To facilitate the use of the methods and resources described in this work, we provide LIANA, a LIgand-receptor ANalysis frAmework as an open-source interface to all the resources and methods.

          Abstract

          Multiple methods to infer cell-cell communication (CCC) from single cell data are currently available. Here, the authors systematically compare 16 CCC inference resources and 7 methods, and develop the LIANA framework as an interface to use and compare all these approaches.

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          Most cited references74

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          KEGG: kyoto encyclopedia of genes and genomes.

          M Kanehisa (2000)
          KEGG (Kyoto Encyclopedia of Genes and Genomes) is a knowledge base for systematic analysis of gene functions, linking genomic information with higher order functional information. The genomic information is stored in the GENES database, which is a collection of gene catalogs for all the completely sequenced genomes and some partial genomes with up-to-date annotation of gene functions. The higher order functional information is stored in the PATHWAY database, which contains graphical representations of cellular processes, such as metabolism, membrane transport, signal transduction and cell cycle. The PATHWAY database is supplemented by a set of ortholog group tables for the information about conserved subpathways (pathway motifs), which are often encoded by positionally coupled genes on the chromosome and which are especially useful in predicting gene functions. A third database in KEGG is LIGAND for the information about chemical compounds, enzyme molecules and enzymatic reactions. KEGG provides Java graphics tools for browsing genome maps, comparing two genome maps and manipulating expression maps, as well as computational tools for sequence comparison, graph comparison and path computation. The KEGG databases are daily updated and made freely available (http://www. genome.ad.jp/kegg/).
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            Integrating single-cell transcriptomic data across different conditions, technologies, and species

            Computational single-cell RNA-seq (scRNA-seq) methods have been successfully applied to experiments representing a single condition, technology, or species to discover and define cellular phenotypes. However, identifying subpopulations of cells that are present across multiple data sets remains challenging. Here, we introduce an analytical strategy for integrating scRNA-seq data sets based on common sources of variation, enabling the identification of shared populations across data sets and downstream comparative analysis. We apply this approach, implemented in our R toolkit Seurat (http://satijalab.org/seurat/), to align scRNA-seq data sets of peripheral blood mononuclear cells under resting and stimulated conditions, hematopoietic progenitors sequenced using two profiling technologies, and pancreatic cell 'atlases' generated from human and mouse islets. In each case, we learn distinct or transitional cell states jointly across data sets, while boosting statistical power through integrated analysis. Our approach facilitates general comparisons of scRNA-seq data sets, potentially deepening our understanding of how distinct cell states respond to perturbation, disease, and evolution.
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              Proteomics. Tissue-based map of the human proteome.

              Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body. Copyright © 2015, American Association for the Advancement of Science.

                Author and article information

                Contributors
                pub.saez@uni-heidelberg.de
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                9 June 2022
                9 June 2022
                2022
                : 13
                : 3224
                Affiliations
                [1 ]GRID grid.7700.0, ISNI 0000 0001 2190 4373, Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, BioQuant, ; Heidelberg, Germany
                [2 ]GRID grid.1957.a, ISNI 0000 0001 0728 696X, Institute for Computational Genomics, Faculty of Medicine, , RWTH Aachen University, ; Aachen, 52074 Germany
                [3 ]GRID grid.412301.5, ISNI 0000 0000 8653 1507, Joint Research Center for Computational Biomedicine, , RWTH Aachen University Hospital, ; Aachen, Germany
                [4 ]GRID grid.11804.3c, ISNI 0000 0001 0942 9821, Faculty of Medicine, Department of Physiology, , Semmelweis University, ; Budapest, Hungary
                [5 ]GRID grid.417570.0, ISNI 0000 0004 0374 1269, Roche Pharma Research and Early Development, , Pharmaceutical Sciences, Roche Innovation Center Basel, ; Basel, Switzerland
                Author information
                http://orcid.org/0000-0003-4125-5643
                http://orcid.org/0000-0001-8391-0031
                http://orcid.org/0000-0003-0087-371X
                http://orcid.org/0000-0003-2890-8697
                http://orcid.org/0000-0001-5482-9023
                http://orcid.org/0000-0002-8552-8976
                Article
                30755
                10.1038/s41467-022-30755-0
                9184522
                35680885
                ee7ba518-2fbd-4583-b5bd-a29121657b39
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 17 June 2021
                : 17 May 2022
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                © The Author(s) 2022

                Uncategorized
                cellular signalling networks,computational platforms and environments,computational models,cancer genomics

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