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      Cellcano: supervised cell type identification for single cell ATAC-seq data

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          Abstract

          Computational cell type identification is a fundamental step in single-cell omics data analysis. Supervised celltyping methods have gained increasing popularity in single-cell RNA-seq data because of the superior performance and the availability of high-quality reference datasets. Recent technological advances in profiling chromatin accessibility at single-cell resolution (scATAC-seq) have brought new insights to the understanding of epigenetic heterogeneity. With continuous accumulation of scATAC-seq datasets, supervised celltyping method specifically designed for scATAC-seq is in urgent need. Here we develop Cellcano, a computational method based on a two-round supervised learning algorithm to identify cell types from scATAC-seq data. The method alleviates the distributional shift between reference and target data and improves the prediction performance. After systematically benchmarking Cellcano on 50 well-designed celltyping tasks from various datasets, we show that Cellcano is accurate, robust, and computationally efficient. Cellcano is well-documented and freely available at https://marvinquiet.github.io/Cellcano/.

          Abstract

          Accurately annotating cell types is a fundamental step in single-cell omics data analysis. Here, the authors develop a computational method called Cellcano based on a two-round supervised learning algorithm to identify cell types for scATAC-seq data and perform benchmarking to demonstrate its accuracy, robustness and computational efficiency.

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          Most cited references44

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          Comprehensive Integration of Single-Cell Data

          Single-cell transcriptomics has transformed our ability to characterize cell states, but deep biological understanding requires more than a taxonomic listing of clusters. As new methods arise to measure distinct cellular modalities, a key analytical challenge is to integrate these datasets to better understand cellular identity and function. Here, we develop a strategy to "anchor" diverse datasets together, enabling us to integrate single-cell measurements not only across scRNA-seq technologies, but also across different modalities. After demonstrating improvement over existing methods for integrating scRNA-seq data, we anchor scRNA-seq experiments with scATAC-seq to explore chromatin differences in closely related interneuron subsets and project protein expression measurements onto a bone marrow atlas to characterize lymphocyte populations. Lastly, we harmonize in situ gene expression and scRNA-seq datasets, allowing transcriptome-wide imputation of spatial gene expression patterns. Our work presents a strategy for the assembly of harmonized references and transfer of information across datasets.
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            Fast, sensitive, and accurate integration of single cell data with Harmony

            The emerging diversity of single cell RNAseq datasets allows for the full transcriptional characterization of cell types across a wide variety of biological and clinical conditions. However, it is challenging to analyze them together, particularly when datasets are assayed with different technologies. Here, real biological differences are interspersed with technical differences. We present Harmony, an algorithm that projects cells into a shared embedding in which cells group by cell type rather than dataset-specific conditions. Harmony simultaneously accounts for multiple experimental and biological factors. In six analyses, we demonstrate the superior performance of Harmony to previously published algorithms. We show that Harmony requires dramatically fewer computational resources. It is the only currently available algorithm that makes the integration of ~106 cells feasible on a personal computer. We apply Harmony to PBMCs from datasets with large experimental differences, 5 studies of pancreatic islet cells, mouse embryogenesis datasets, and cross-modality spatial integration.
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              Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage

              Tissue fibrosis is a major cause of mortality that results from the deposition of matrix proteins by an activated mesenchyme. Macrophages accumulate in fibrosis, but the role of specific subgroups in supporting fibrogenesis has not been investigated in vivo. Here we used single-cell RNA sequencing (scRNA-seq) to characterize the heterogeneity of macrophages in bleomycin-induced lung fibrosis in mice. A novel computational framework for the annotation of scRNA-seq by reference to bulk transcriptomes (SingleR) enabled the subclustering of macrophages and revealed a disease-associated subgroup with a transitional gene expression profile intermediate between monocyte-derived and alveolar macrophages. These CX3CR1+SiglecF+ transitional macrophages localized to the fibrotic niche and had a profibrotic effect in vivo. Human orthologues of genes expressed by the transitional macrophages were upregulated in samples from patients with idiopathic pulmonary fibrosis. Thus, we have identified a pathological subgroup of transitional macrophages that are required for the fibrotic response to injury.
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                Author and article information

                Contributors
                wuhao@siat.ac.cn
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                3 April 2023
                3 April 2023
                2023
                : 14
                : 1864
                Affiliations
                [1 ]GRID grid.189967.8, ISNI 0000 0001 0941 6502, Department of Computer Science, , Emory University, ; 400 Dowman Drive, Atlanta, GA 30322 USA
                [2 ]GRID grid.263488.3, ISNI 0000 0001 0472 9649, Faculty of Computer Science and Control Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 1068 Xueyuan Avenue, , Shenzhen University Town, ; Shenzhen, 518055 P. R. China
                [3 ]GRID grid.189967.8, ISNI 0000 0001 0941 6502, Department of Biostatistics and Bioinformatics, Rollins School of Public Health, , Emory University, ; 1518 Clifton Road NE, Atlanta, GA 30322 USA
                Author information
                http://orcid.org/0000-0001-8757-651X
                http://orcid.org/0000-0001-9052-6951
                http://orcid.org/0000-0003-1269-7354
                Article
                37439
                10.1038/s41467-023-37439-3
                10070275
                37012226
                5b49a68c-5a03-40dd-8d31-2b501f67105c
                © The Author(s) 2023

                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
                : 20 June 2022
                : 15 March 2023
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000002, U.S. Department of Health & Human Services | National Institutes of Health (NIH);
                Award ID: R01GM122083
                Award Recipient :
                Funded by: Strategic Priority Research Program of Chinese Academy of Sciences, Grant No. XDB38050100
                Categories
                Article
                Custom metadata
                © The Author(s) 2023

                Uncategorized
                computational models,machine learning,software,computational science
                Uncategorized
                computational models, machine learning, software, computational science

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